Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC₅₀ values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

Membrane transporters (MTs) are mainly localized at the plasma membrane (PM), tonoplast and vacuolar membrane (VM) of cells in all plant organs. Their work is to maintain the cellular homeostasis by controlling ionic movements across PM channels from roots to upper plant parts, xylem loading and remobilization of sugar molecules from photosynthesis tissues in the leaf (source) to roots, stem and seeds (sink) via phloem loading. The plant’s whole source-to-sink relationship is regulated by multiple transporting proteins in a highly sophisticated manner and driven based on different stages of plant growth and development (PG&D), and environmental changes. The MTs play a pivotal role in PG&D in terms of increased plant height, branches/tiller numbers, enhanced numbers, length and filled panicles per plant, seed yield and grain quality. Dynamic climatic changes disturbed the ionic balance (salt, drought and heavy metals) and sugar supply (cold and heat stress). Due to poor selectivity, some of the MTs also uptake toxic elements in the roots that negatively impact on PG&D, later on also exported to upper parts and then deteriorate the grain quality. As an adaptive strategy, in response to salt and HMs plants activated PM and VM localized MTs that export toxic elements into vacuole, and also translocate in the root’s tips and shoot. However, in case of drought, cold and heat stresses, MTs increased the water and sugar supply to all organs. In this review, we mainly reviewed recent literature from Arabidopsis, halophytes, and major field crops such as rice, wheat, maize and oilseed rape to argue on the global role of MTs in PG&D and abiotic stress tolerance. We also discussed the gene expression level changes and genomic variations within a species as well as within a family in response to developmental and environmental cues.

Non-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. Here, the aim of this study was to investigate the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field. Our findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells and. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. Therefore, DSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21^st Century Biology.

Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by systematic divisions. Metazoans attain structural complexity with exquisite precision, which is a molecular mystery. The indispensable role of centrioles in cell division and ciliogenesis can shed insight into this riddle. Cell division helps in growth of the body and is a highly regulated and integrated process. Its errors cause malignancies. The cell mass is organized during organogenesis. Prior to it, the centrioles are retrieved from the cell cycle to initiate ciliogenesis. The cilia-modulated developmental signaling pathways elaborate the body plan. The secluded compartment of the cilium reduces noise during signaling and is essential for a precise body plan development. The dysfunctional centrioles and cilia can distort body plan. Thus, centriole has a dual role in growth and cellular organization. This concept review analyses the comprehensive interactome and the key domain features (like C2 domain) of molecules which connect and disarm the centriole from the cell cycle and ciliogenesis by switching on or off the essential regulators of the pathways. The concentration of these signaling pathways at the centriole reinforces the hypothesis that centriole is the molecular workstation to carve out structural design and complexity in metazoans.

Hearing impairment is an immensely diagnosed genetic cause, 5% of the total world population effects with different kind of congenital hearing loss (HL). In third-world countries or countries where consanguineous marriages are more common the frequency rate of genetic disorders are at its zenith. Approximately, the incidence of hearing afflictions is ostensibly 7-8:1000 individuals whereas it is estimated that about 466 million peoples suffer with significant HL, and of theses deaf cases 34 million are children’s up to March, 2020. Several genes and colossal numbers of pathogenic variants cause hearing impairment, which aided in next-generation with recessive, dominant or X-linked inheritance traits. This review highlights on syndromic and non-syndromic HL (SHL and NSHL), and categorized as conductive, sensorineural and mixed HL, which having autosomal dominant and recessive, and X-linked or mitochondrial mode of inheritance. Many hundred genes involved in HL are reported, and their mutation spectrum becomes very wide. Mapping of pathogenic genes in consanguinity family is facilitated to understand the disease history. Review presents the bases of HL and also focused on various genetic factors that cause deafness like the basics of genetic inheritance, and classic and well-characterized inherited factors of it. It also overviews the application of linkage analysis, SNPs genotyping and whole exome sequencing methods, in mapping and identification of new locus, causative genes and their variants in families inherited with HL. Conclusively, this review supports researchers in understanding the location of chromosome, the causative genes and specific locus which causing deafness in humans.

Abstract: A large number of collecting expeditions were launched in regions of ‘centers of diversity’ and hundreds of thousands of sample have been collected and stored in gene banks as ‘genetic resources’. So far, only a small number of the samples have been evaluated for their biotic and abiotic stress tolerance. Now, their time to become useful has come. A new global phenomenon has arisen – climate change. The crop genetic resources and their wild progenitors that have survived countless years of changing environment during the last 11,000 years could harbor genes that may be useful under the new growing conditions and environmental factors thrown up by climate change and global warming. With the deployment of modern bio-engineering techniques selected genes or gene fragments can be transferred from genetic resources to modern varieties of crop plants to make them well-prepared to mitigate the effects of global warming and climate change. The latter is the most serious issue facing plant breeders today. New pests and diseases could affect crop production. These review paper discusses various impacts and issues as a result of this phenomenon and suggest ways to safeguard our most important crops through better management of crop plant genetic resources in the near future.

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

The study explores antibacterial, antiinflammatory and cytoprotective capacity of Pelargonium sidoides DC root extract (PSRE) and proanthocyanidin fraction from PSRE (PACN) under conditions characteristic for periodontal disease. Following previous finding that PACN exerts stronger suppression of Porphyromonas gingivalis compared to the effect on commensal Streptococcus salivarius, the current work continues antibacterial investigation on Staphylococcus aureus, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans and Escherichia coli. PSRE and PACN are also studied for their ability to prevent gingival fibroblast cell death in the presence of bacteria or bacterial lipopolysaccharide (LPS), to block LPS- or LPS+IFNγ-induced release of inflammatory mediators, gene expression and surface antigen presentation. Both PSRE and PACN were more efficient in suppressing Staphylococcus and Aggregatibacter compared to Escherichia, prevented A. actinomycetemcomitans- and LPS induced death of fibroblasts, decreased LPS-induced release of interleukin 8 and prostaglandin E2 from fibroblasts and IL-6 from leukocytes, blocked expression of IL-1β, iNOS, and surface presentation of CD80 and CD86 in LPS+IFNγ-treated macrophages, and IL-1β and COX-2 expression in LPS-treated leukocytes. None of the investigated substances affected either the level of secretion or expression of TNFα. In conclusion, PSRE, and especially PACN, possess strong antibacterial, antiinflammatory and gingival tissue protecting properties under periodontitis mimicking conditions and are suggestable candidates for treatment of the disease.

Background: Ongoing molecular profiling studies enabled by advances in biomedical technologies are producing vast amounts of ‘omic’ data for early detection, monitoring, and prognosis of diverse diseases. A major common limitation is the scarcity of biological samples, necessitating integrative modeling frameworks that can make optimal use of available data for disease classification tasks. Related data sets are often available from different studies, but may have been generated using different technology platforms. Thus, there is a critical need for flexible modeling methods that can handle data from diverse sources to facilitate the discovery of robust biomarkers that underlie disease regulatory processes. Results: In this paper, we introduce a novel framework called Knowledge Augmented Rule Learning (KARL), which incorporates two sources of knowledge, domain, and data, for pattern discovery from small and high-dimensional datasets, such as transcriptomic data. We propose KARL as a transfer rule learning framework in which knowledge of the domain is transferred to the learning process on data in order to 1) improve the reliability of the discovered patterns, and 2) study the knowledge of the domain when used along with data for modeling. In this work, we generated KARL models on gene expression datasets for five types of cancer, including brain, breast, colon, lung, and prostate. As our knowledge of the domain, we used the Ingenuity Knowledge Base (IKB) to extract genes related to hallmarks of cancer and annotated these prior relationships before learning classifiers from these datasets. Conclusions: Our results show that KARL produces, on average, rule models that are more robust classifiers than the baseline without such background knowledge, for our tasks of cancer prediction using 25 publicly available gene expression datasets. Moreover, KARL helped us learn insights about previously known relationships in these gene expression datasets, along with new relationships not input as known, to enable informed biomarker discovery for cancer prediction tasks. KARL can be applied to modeling similar data from any other domain and classification task. Future work would involve extensions to KARL to handle hierarchical knowledge to derive more general hypotheses to drive biomedicine.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

This study introduces a cascade nonlinear proportional integral retarded (CNPIR) controller for the first time in the literature, aiming to achieve real-time precise control of a double-tank liquid level system. It begins by outlining the characteristics of de-lay-based systems and detailing the dynamic behavior of the liquid-level system. The study evaluates the system's performance by developing and analyzing the mathe-matical models of both the feedforward proportional-integral (FF-PI) controller and the CNPIR controller. Two different control techniques were employed, with real-time tests conducted to assess the system's axis movement performance. The FF-PI controller was used as the initial control technique, while the CNPIR controller was introduced to enhance system performance during trajectory tracking. Experimental results demon-strated that the CNPIR method significantly improved trajectory tracking response, reduced overshoot, and achieved better steady-state error under external disturbances compared to the FF-PI controller. Thus, the experimental study, highlights the effec-tiveness of the proposed control design and its superiority over some existing classical methods.

The delineation of the clinical target volumes (CTVs) for radiation therapy is time-consuming, requires intensive training and shows high inter-observer variability. Supervised deep learning methods depend heavily on consistent training data, thus state-of-the-art research focuses on making CTV labels more homogeneous and strictly bounding them to current standards. International consensus expert guidelines standardize CTV delineation by conditioning the extension of the clinical target volume on surrounding anatomical structures. Training strategies that directly following the construction rules given in the expert guidelines or the possibility to quantify the conformance of manually drawn contours with the guidelines are still missing. 71 anatomical structures that are relevant for CTV delineation in head and neck cancer patients according to the expert guidelines were segmented on 104 CT scans to assess the possibility to automate their segmentation by state-of-the-art deep learning methods. nnU-Net models were trained to automatically segment those 71 structures on planning CT scans. We report the DICE, HD and sDICE for 71 + 5 anatomical structures for most of which no previous segmentation accuracies have been reported. For those structures, for that prediction values have been reported, our segmentation accuracy matched or exceeded the reported values. The predictions from our models were always better than those predicted by the TotalSegmentator. The sDICE with 2mm margin was larger than 80% for almost all structures. Individual structures with decreased segmentation accuracy are analyzed and discussed with respect to their impact on the CTV delineation following the expert guidelines. No deviation is expected to affect the rule-based automation of the CTV delineation.

Higher traffic density in Russian cities and less uniform traffic due to congestions are reasons for increased emissions of pollutants contained in exhaust gases of vehicles. The paper presents the modeling results of pollutant dispersion in Magnitogorsk. The analysis of these results shows that now many blocks of flats and social infrastructure of the city are in a zone with an excess of maximum allowable concentration of pollutants. Having summarized the methodological framework formulated by Russian and foreign researchers, the authors systemized the existing methods used to decrease pollutants produced by vehicles. It is proposed to choose an optimal combination of such methods applying a developed mathematical model. By adopting an optimal combination of the methods, it is possible to ensure minimum air pollutant emissions from vehicles, allocating limited financial resources. The mathematical modeling of the solutions on changing traffic density and structure and implementing methods used to decrease pollutants on one of the Magnitogorsk crossroads with the heaviest traffic is used to draw a conclusion about efficiency of the designed model used as a tool for strategic planning of development and transformation of street networks.

This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.

Object-level Simultaneous Localization and Mapping (SLAM) has gained popularity in recent years since it can provide a means for intelligent robot-to-environment interactions. However, most of these methods assume that the distribution of the errors is gaussian. This assumption is not valid under many circumstances. Further, these methods use a delayed initialization of the objects in the map. During this delayed period, the solution relies on the motion model provided by an Inertial Measurement Unit (IMU). Unfortunately, the errors tend to accumulate quickly due to the dead-reckoning nature of these motion models. Finally, the current solutions depend on a set of salient features on the object’s surface and not the object’s shape. This research proposes an accurate object-level solution to the SLAM problem with a 4.1 to 13.1 cm error in the position (0.005 to 0.021 of the total path). The developed solution is based on Rao-blackwellized Particle Filtering (RBPF) that does not assume any predefined error distribution for the parameters. Further, the solution relies on the shape and thus can be used for objects that lack texture on their surface. Finally, the developed tightly coupled IMU/camera solution is based on an undelayed initialization of the objects in the map.

The Multi-Level Model (=MLM) was suggested by A. Levichev as a description of quarks and gluons. The review recalls MLM-terminology while MLM-findings (for quarks and leptons) are compared to the theoretical and experimental data as accepted by the Standard Model (=SM). MLM is based on Segal’s compact space-time U(2) and on the sequence of embeddings: U(2) into U(3), U(2) into U(4), etc. These groups were called the levels (of matter): U(2) - the 0th (that is, our mundane world), U(3) - the 1st, U(4) - the 2nd, etc. Such a convention matches the SM-quarks' generations list. Each SM-quark is viewed either as a sunken proton, or as a captured proton. The MLM-proton is elementary and indestructible (hence no need for confinement). For MLM-quarks, in terms of the notion of a ruling group, flavor and color are defined mathematically. The number of colors (and of flavors) is level-dependent. For levels U(3) through U(6) the correspondence with the SM-quarks is established. Three new quarks and two new leptons are predicted. The SM-puzzle of quark and lepton generations is solved. Using the Han-Nambu scheme, the notion of the quark’s electric charge is expressed in terms of color charges. The original part of the review suggests studying the proton’s properties (like mass, shape and inner pressure) on the ba-sis of its wave function.

The planetary boundary layer height (PBLH) is one of the key factors in influencing the dispersion of the air pollutants in the troposphere and hence the air pollutant concentration on ground level. For this reason, accurate air pollutant concentration depends on the performance of PBLH prediction. Recently, ceilometer, a lidar instrument to measure cloud base height, has been used by atmospheric scientists and air pollution control authorities to determine the mixing level height (MLH) in improving forecasting and understanding the evolution of aerosol layers above ground at a site. In this study, ceilometer data at an urban (Lidcombe) and a rural (Merriwa) location in the New South Wales, Australia was used to validate the PBLH prediction from two air quality models (CCAM-CTM and WRF-CMAQ) as well as to understand the aerosol transport from sources to receptor point at Merriwa for the three case studies where high PM10 concentration was detected in each of the three days. The results show that the PBLH prediction by the two air quality models corresponds reasonably well with observed ceilometer data and the cause and source of high PM10 concentration at Merriwa can be found by using ceilometer MLH data to corroborate with back trajectory analysis of transport of aerosols to the receptor point at Merriwa. Of the three case studies, one had aerosol source from north and north west of Merriwa in remote NSW where windblown dust is the main source, and the other two had sources from south and south east of Merriwa where anthropogenic sources dominate,

Spent nuclear fuel and high-level radioactive waste can be disposed in deep horizontal drillholes in sedimentary, metamorphic, or igneous rocks. Horizontal drillhole disposal has safety, operational, and economic benefits: The repository is deep in the brine-saturated zone far below aquifers in a reducing environment of formations that can be shown to have been isolated from the surface for millions of years; its depth provides safety against inadvertent intrusion, earth¬quakes, and near-surface perturbations; it can be placed close to the reactors and interim storage facilities, minimizing transportation; disposal costs per ton of waste can be kept substantially lower than for mined repositories by its smaller size, reduced infrastructure needs, and staged imple¬mentation; and, if desired, the waste could be retrieved using “fishing” technology. In the proposed disposal concept, corrosion-resistant canisters containing unmodified fuel assemblies from commercial reactors would be placed end-to-end in up to 50 cm diameter horizontal drill¬holes, a configuration that reduces mechanical stresses and keeps the temperatures below the boiling point of the brine. Other high-level wastes, such as capsules containing 137Cs and 90Sr, can be disposed in small-diameter drillholes. We provide an overview of this novel disposal concept and its technology, discuss some of its safety aspects, and compare it to mined repositories and the deep vertical borehole disposal concept.

Delineating the cropping area of cocoa agroforests is a major challenge for quantifying the contribution of the land use expansion to tropical deforestation. Discriminating cocoa agroforests from tropical transition forests using multi-spectral optical images is difficult due to a similarity in the spectral characteristics of their canopy; moreover, optical sensors are largely impeded by the frequent cloud cover in the tropics. This study explores multi-season Sentinel-1 C-band SAR image to discriminate cocoa agroforests from transition forests for a heterogeneous landscape in central Cameroon. We use an ensemble classifier, random forest, to average SAR image texture features of GLCM (Grey Level Co-occurrence Matrix) across seasons; next, we compare classification performance with results from RapidEye optical data. Moreover, we assess the performance of GLCM texture feature extraction at four different grey level quantization: 32bits, 8bits, 6bits, and 4bits. The classification overall accuracy (OA) of texture-based maps outperformed that from an optical image; the highest OA of 88.8% was recorded at 6bits grey level. This quantization level, in comparison to the initial 32bits in SAR images, reduced the class prediction error by 2.9%. Although this prediction gain may be large for the landscape area, the resultant thematic map reveals the decrease and fragmentation of forest cover by cocoa agroforests. According to our classification validation, the Shannon entropy (H) or uncertainty provides a reliable validation for class predictions and reveals detail inference for discriminating inherently heterogeneous vegetation categories. The texture-based classification achieved a reliable accuracy considering the heterogeneity of the landscape and vegetation classes.

The popular motor drive systems with a single two-level voltage source inverter (VSI) have one main problem that is the occurrence of the common-mode voltage (CMV), which is an effect of the electromagnetic interference, shaft voltage, bearing currents, leakage current. These cause the high stress, increasung temperature and early mechanical failure in machine. To overcome this problem, the technology of the dual two-level VSI fed open-end three-phase ac loads is now available to eliminate the CMV at the ac/induction motor load with the 120-degree modulation technique for controlling each inverter. In this paper, the discontinuous space vector modulation (DSVM) schemes are proposed and applied for the dual two-level VSI fed open-end load. It is based on the 120-degree modulation technique by using only 12 active voltage vectors and the 10 zero voltage vectors from the total 64 voltage vectors along with the different five-segment swicthing sequence designs with centralizing pulse width modulation technqiue in order to not only cancel the CMV in the ac load, but also reduce the switching number/switching loss of the conversion system. Among the various DSVM schemes, their performances are compared in this paper, such as the number of the switching, the step and peak value of the CMV in each inverter, and the quality of the output waveform, etc. The details of the verfication and comparison are carried out by simulation using Matlab/Simulink software.

Rice, a globally important food crop, faces significant challenges due to salt and drought stress. These abiotic stresses severely impact rice growth and yield, manifesting as reduced plant height, decreased tillering, reduced biomass, and poor leaf development. Recent advances in molecular biology and genomics have uncovered key physiological and molecular mechanisms that rice employs to cope with these stresses, including osmotic regulation, ion balance, antioxidant re-sponses, signal transduction, and gene expression regulation. Transcription factors such as DREB, NAC, and bZIP, as well as plant hormones like ABA and GA, have been identified as crucial reg-ulators. Utilizing CRISPR/Cas9 technology for gene editing holds promise for significantly en-hancing rice stress tolerance. Future research should integrate multi-omics approaches and smart agriculture technologies to develop rice varieties with enhanced stress resistance, ensuring food security and sustainable agriculture in the face of global environmental changes.

In the face of rising global demand and unsustainable production methods, cultivated crustacean meat (CCM) is proposed as an alternative means to produce delicious lobster, shrimp and crab products. Cultivated meat requires starting stem cells that may vary in terms of potency, and propensity to proliferate or differentiate into myogenic (muscle-related) tissues. We suggest that regenerating crustacean limbs harbor a range of stem cells suitable for cultivated meat production and present a humane tissue source because they can be accessed non-lethally. To investigate stem cell activity in this model, we have conducted RNA-Seq analysis across six stages of claw regeneration in the crayfish Cherax quadricarinatus (four pre-molt and two post-molt stages), along with histology and real time quantitative PCR (qPCR). Differential expression analysis revealed expression patterns of significantly up- or down-regulated genes in 14 functional categories. Relative expression of select stem cell target genes (including endocrine, myogenic, cell cycle and pluripotency factors) highlighted two growth peaks during pre-molt regeneration and limited stem cell activity after the molt. Histology and qPCR results support the overall finding that pre-molt limb regeneration stages harbor more stem cell activity, likely making them a more prolific cell source for CCM development.

Introduction: Transforming growth factor beta receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, and the paracrine signaling that guides sensory innervation in developing mouse molars. We hypothesized that Tgfbr2 also regulates the neuro-pulpal responses to injury to activate axon sprouting and tertiary dentin secretion. Methods: We per-formed a timed deletion of Tgfbr2 using tetracycline-responsive Osterix-Cre;Tgfbr2f/f (Tgfbr2^cko) mice, which allowed them to develop normally. At 3 months, we drilled a shallow hole on the mesial side of the first mandibular molar (M1) in both control and Tgfbr2^cko mice. Hemi-mandibles were collected 4, 8, 21, and 56 days post-injury (dpi). In situ hybridization (ISH) for Sp7 was performed to confirm Osterix-Cre transcription. Microcomputed tomography (micro-CT) imaging and histology were used to examine the tertiary dentin, and immunofluorescence was used to visualize CGRP+ axons following the injury. Results: Tgfbr2 deletion was inferred by Sp7 ISH. Micro-CT and histology indicated a lower dentin volume in 21 dpi Tgfbr2^cko M1s compared to WT M1s, but the volume was comparable by 56 dpi. The duration of axon sprouting was longer in injured Tgfbr2^cko M1s compared to WT M1s. Conclusions: These results suggest that sensory afferents may support dentin repair in Tgfbr2-deficient odontoblasts.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C>T; c.748C>T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C>T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P<0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Recently intraductal carcinoma of the prostate (IDCP) has attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced accessibility to immune cells, which reflect the pathological characteristics of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversify alterations in the microbial and host co-metabolites. The main mechanism of bacterial evolution is horizontal gene transfer (HGT) and acquisition of new traits can be achieved through mobile genetic element (MGEs) exchange. Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to august 2023, using appropriate MeSH entry terms were performed. GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cells inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability and biocontainment and many other aspects are only partially controlled and harmful consequences for public health should be avoided. Always remember that prevention is the most cost- effective strategy and "primum non nocere" is the name of the game.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS) for malnourished (or at-risk) hemodialysis patients with a "similar to the Mediterranean diet" model, improved caloric and protein intake, nutritional status and inflammation and oxidation biomarkers. Our aim in this study was to evaluate whether the new ONS, including probiotics, may produce changes in miRNAs expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We conducted a randomized, multicenter, parallel-group study in malnourished hemodialysis patients divided in 3 groups (1: Control -C- individualized diet 2: Oral nutritional supplement -ONS- + placebo -ONS-PL- and 3: ONS + probiotics -ONS-PR). Study registration: NCT03924089. The trial was open to the ONS diet or individual dietary advice, but double-blind for the intake of probiotics supplements. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3-months in comparison with baseline. LEPTIN expression was significantly increased in ONS-PL group at 3-month intervention compared to baseline. The new Oral Nutritional Supplement associated with probiotics; increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this Oral Nutritional Supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

Mallard (Anas platyrhynchos) are currently one of the most popular species in rare bird breeding in several southern provinces of China, but there are very few studies on the gut microbial communities of domestic and wild mallards. In this study, 16S rRNA gene high-throughput sequencing technology was used to compare the composition and diversity of gut microbial communities in domestic and wild mallards. Alpha diversity analysis revealed significant differences in the gut microbial communities of domestic and wild mallards. Beta diversity analysis showed that the two groups of stool samples were mostly separated on the principal coordinate analysis (PCOA) plot. In domestic mallards, Firmicutes (67.97%) was the most abundant bacterial phylum, followed by Proteobacteria (24.48%), Bacteroidetes (3.13%), Fusobacteria (2.21%), and Actinobacteria (1.10%). The dominant bacterial phyla in wild mallards were Firmicutes (79.02%), Proteobacteria (12.85%), Fusobacteria (3.37%), and Bacteroidetes (2.79%). At the genus level, a total of 10 dominant genera (Streptococcus, Enterococcus, Clostridium, Lactobacillus, Soilbacillus, Bacillus, Acinetobacter, Comamonas, Shigella, and Cetobacterium) with an average relative abundance greater than 1% were detected in the fecal samples of both groups. The average relative abundance of five potential pathogens (Streptococcus, Enterococcus, Acinetobacter, Comamonas, and Shigella) was higher in domestic mallards than in wild mallards. The enrichment of pathogenic bacteria in the intestinal tract of domestic mallards should be of sufficient concern.

Mallard (Anas platyrhynchos) are currently one of the most popular species in rare bird breeding in several southern provinces of China, but there are very few studies on the gut microbial communities of domestic and wild mallards. In this study, 16S rRNA gene high-throughput sequencing technology was used to compare the composition and diversity of gut microbial communities in domestic and wild mallards. Alpha diversity analysis revealed significant differences in the gut microbial communities of domestic and wild mallards. Beta diversity analysis showed that the two groups of stool samples were mostly separated on the principal coordinate analysis (PCOA) plot. In domestic mallards, Firmicutes (67.97%) was the most abundant bacterial phylum, followed by Proteobacteria (24.48%), Bacteroidetes (3.13%), Fusobacteria (2.21%), and Actinobacteria (1.10%). The dominant bacterial phyla in wild mallards were Firmicutes (79.02%), Proteobacteria (12.85%), Fusobacteria (3.37%), and Bacteroidetes (2.79%). At the genus level, a total of 10 dominant genera (Streptococcus, Enterococcus, Clostridium, Lactobacillus, Soilbacillus, Bacillus, Acinetobacter, Comamonas, Shigella, and Cetobacterium) with an average relative abundance greater than 1% were detected in the fecal samples of both groups. The average relative abundance of five potential pathogens (Streptococcus, Enterococcus, Acinetobacter, Comamonas, and Shigella) was higher in domestic mallards than in wild mallards. The enrichment of pathogenic bacteria in the intestinal tract of domestic mallards should be of sufficient concern.

It has long been known that phytohormone auxin plays a promoting role in tuber formation and stress tolerance in potatoes. Our study aimed to identify and characterize the complete sets of auxin-related genes that presumably constitute the entire auxin signaling system in potato (Solanum tuberosum L.). The corresponding genes were retrieved from sequenced genomes of the doubled monoploid S. tuberosum DM1-3-516-R44 (DM) of the Phureja group, the heterozygous diploid line RH89-039-16 (RH), and the autotetraploid cultivar Otava. Both canonical and noncanonical auxin signaling pathways were considered. Phylogenetic and domain analyzes of deduced proteins were supplemented by their expression profiling and 3D molecular modeling. The canonical and ABP1-mediated pathways of auxin signaling appeared to be well conserved. Total number of potato genes/proteins presumably involved in canonical auxin signaling is 46 and 108 in monoploid DM and tetraploid Otava, respectively. Among studied potatoes, spectra of expressed genes obviously associated with auxin signaling were partly cultivar-specific and quite different from analogous spectrum in Arabidopsis. Most of the noncanonical pathways found in Arabidopsis appeared to be low probable in potato. This was equally applied to all cultivars used irrespective of their ploidy. Thus, some important features of the (noncanonical) auxin signaling pathways may be variable and species-specific.

During the infection by SARS-CoV-2, the virus is changing infected host cell into its own factory producing new viral particles. As infection progresses, infected cell undergoes many changes in various pathways. One of the events caused by changes is cytokine storm, which leads to the severe symptoms. In this study, we investigated transcriptomic changes caused by COVID-19 disease using RNA-seq data obtained from COVID-19-positive patients and COVID-19-negative donors. RNA-seq data were collected for the purpose of identification of potential biomarkers associated with a different course of the disease. Here, the first datasets of 96 samples were analyzed to validate the methods. The aim of this publication is to report pilot results. In search of potential biomarkers associated with different disease severity, we performed differential expression analysis of human transcriptome, focusing on COVID-19 positivity and symptom severity. Since we detected plenty of potential biomarkers, we performed KEGG enrichment analysis to get better view of altered pathways. Results show, that affected were pathways related to immune processes and response to infection, also multiple signaling pathways, while most of them were also reported to be influenced by SARS-CoV-2 infection in previous studies.

The human polyamines spermine and spermidine are essential for cell function, and their properties have been extensively studied. However, research results of experiments conducted without understanding the properties of polyamines have been evaluated and published by reviewers who appear to have little knowledge of the properties of polyamines. It is sad that some studies repeat what was done more than half a century ago before polyamines were characterized. First, I explain the basic properties of polyamines that researchers need to know. Then, the relationship between changes in polyamine levels in the body and age- and lifestyle-related diseases is discussed. In addition, the epigenetic mechanism of action of polyamines in relation to healthy longevity and, conversely, age- and lifestyle-related diseases and the progression of senescence are discussed. Spermine, which increases with a polyamine-rich diet, acts to suppress aberrant gene methylation and proinflammatory status associated with aging. Meanwhile, chronic inflammation associated with aging induces the enzyme activity of spermine oxidase, which breaks down spermine and produces acrolein, resulting in reduced spermine levels. Acrolein, a toxic aldehyde that increases with age- and lifestyle-related diseases, is thought to accelerate these diseases.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles in two widely used mouse models of septic cardiomyopathy, the cecal ligation and puncture (CLP) model and the lipopolysaccharide (LPS) model. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings suggested that 1) both methods can induce septic heart dysfunction within 24 hours; 2) distinct whole transcriptome expression profiles are revealed; 3) potentially different pathways are involved in causing heart failure in sepsis. The comprehensive comparison provides valuable insights into the molecular basis of septic cardiomyopathy and contributes to the ongoing search for effective treatment strategies, triggered by different factors for SICM.

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell-level to the cell group. This reorganization of fitness occurs by allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group – soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life-history genes present in the unicellular ancestors of a multicellular lineage. Single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival when stressed. Such stress response life-history genes can provide the foundation for the genetic basis for cellular differentiation in multicellular lineages. The regA gene family in volvocine green algae provides a model system to study how this co-option occurs. We discuss the origin and evolution of the volvocine regA gene family, including regA – the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA family a useful template for similar investigations in other lineages.

This paper presents a computational approach designed to construct and query a literature-based knowledge graph for predicting novel drug therapeutics. The main objective is to offer a platform that discovers drug combinations from FDA-approved drugs and accelerates their investigations by domain scientists. Specifically, the paper introduced the following algorithms: (1) an algorithm for constructing the knowledge graph from drug, gene, and disease mentions in the biomedical literature; (2) an algorithm for vetting the knowledge graph from drug combinations that may pose a risk of drug interaction; (3) and two querying algorithms for searching the knowledge graph by a single drug or a combination of drugs. The resulting knowledge graph had 844 drugs, 306 gene/protein features, and 19 disease mentions. The original number of drug combinations generated was 2,001. We queried the knowledge graph to eliminate noise generated from chemicals that are not drugs. This step resulted in 614 drug combinations. When vetting the knowledge graph to eliminate the potentially risky drug combinations, it resulted in predicting 200 combinations. Our domain expert manually eliminated extra 54 combinations which left only 146 combination candidates. Our three-layered knowledge graph, empowered by our algorithms, offered a tool that predicted drug combination therapeutics for scientists who can further investigate from the viewpoint of drug targets and side effects.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

Drought events are predicted to become more prevalent in the future. Evaluating the performance of herbicide-resistant and susceptible weed ecotypes to progressive drought can provide insights into whether resistance trait(s) increased or reduced the fitness of a resistant population. Two experiments were conducted in the greenhouse between January and May 2021 to evaluate drought tolerance differences between Palmer amaranth accessions resistant to S-metolachlor or glyphosate and their susceptible counterparts. The accessions used were: S-metolachlor-resistant (17TUN-A), a susceptible standard (09CRW-A), and glyphosate-resistant (22 to 165 EPSPS copies) and glyphosate-susceptible (3 to 10 EPSPS copies) plants from accession 16CRW-D. Daily transpiration of each plant was measured. The daily transpiration rate was converted to normalized transpiration ratio (NTR) using a double-normalization procedure. The daily soil water content was expressed as a fraction of transpirable soil water (FTSW). The threshold FTSW (FTSWcr), after which NTR decreases linearly, was estimated using a two-segment linear regression analysis. The data showed differences between S-metolachlor- resistant and -susceptible accessions (P ≤ 0.05). The FTSW remaining in the soil at the breakpoint for the S-metolachlor-susceptible accession (09CRW-A) was 0.17±0.007. The FTSW remaining in the soil at the breakpoint for the S-metolachlor-resistant accession (17TUN-A) was 0.23±0.004. Although the mechanism endowing resistance to S-metolachlor might have contributed to increased drought tolerance, follow-up experiments are needed to verify this finding. Increased EPSPS copy number did not improve drought tolerance of Palmer amaranth.

In a changing climate, extreme weather events such as heat waves will be more frequent and could affect grain weight and the quality of crops such as wheat, one of the most significant crops in terms of global food security. In this work, we characterized the response of Triticum turgidum spp. durum wheat to a short-term heat-stress (HS) treatment at transcriptomic and physiological levels during early grain filling in glasshouse experiments. We found a significant reduction in grain weight and size from HS treatment. Grain quality was also affected, showing a decrease in starch content in addition to increments in grain protein levels. Moreover, an RNA-seq analysis of durum wheat grains allowed us to identify 1590 differentially expressed genes related to photosynthesis, response to heat, and carbohydrate metabolic process. A gene regulatory network analysis of HS-responsive genes uncovered novel transcription factors (TFs) controlling the expression of genes involved in abiotic stress response and grain quality, such as a member of the DOF family predicted to regulate glycogen and starch biosynthetic processes in response to HS in grains. In summary, our results provide new insights into the extensive transcriptome reprogramming that occurs during short-term HS in durum wheat grains.

The Sugarcane yellow leaf virus (SCYLV) is associated with sugarcane yellow leaf disease (SCYLD) and is considered to be the most economically deleterious emerging pathogen that represents a potential threat and danger to sugarcane cultivation in China. Over the last two decades, high genetic diversity in the SCYLV genotypes was observed worldwide, with a greater chance of YLD incidence for sugarcane injury. SCYLV infection has significantly damaged its economic traits and is responsible for substantial losses in biomass production in sugarcane cultivars. This study aims to identify and comprehensively analyze sugarcane microRNAs (miRNAs) as therapeutic targets against SCYLV using plant miRNA prediction tools. Mature sugarcane miRNAs are retrieved and are used for hybridization of the SCYLV. A total of seven common sugarcane miRNAs were selected based on consensus genomic positions. The biologically significant, top ranked ssp-miR528 was consensually predicted to have a potentially unique hybridization site at nucleotide position 4162 for targeting the ORF5 of the SCYLV genome; this was predicted by all the algorithms used in this study. Then, the miRNA–mRNA regulatory network was generated using the Circos algorithm, which was used to predict novel targets. There are no acceptable commercial SCYLV-resistant sugarcane varieties available at present. Therefore, the predicted biological data offer valuable evidence for the generation of SCYLV-resistant sugarcane plants.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.

Until recently, research on the molecular signatures of HPV-associated head and neck cancers mainly focused on their differences with respect to HPV-negative HNSCCs. However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells, and oxidoreductive processes all play important roles.

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

Bacterial conjugation, also referred to as bacterial sex, is a major horizontal gene transfer mechanism where the DNA is transferred from a donor to a recipient bacterium by direct contact. Conjugation is universally conserved among bacteria and occurs in a wide range of environments (soil, plant surfaces, water, sewage, biofilms and host-associated bacterial communities). Within these habitats, conjugation drives the rapid evolution and adaptation of bacterial strains by mediating the propagation of various metabolic properties, including symbiotic life-style, virulence, biofilm formation, or resistance to heavy metals and, most importantly, resistance to antibiotics. These properties make of conjugation a fundamentally important process at the center of extensive study. Here, we review the key steps of conjugation by following the life-cycle of the F plasmid during transfer from the donor to the recipient cell. We also discuss our current knowledge of the extent and impact of conjugation within an environmentally and clinically relevant bacterial habitat, bacterial biofilms.

GIGANTEA (GI) is a gene involved in multiple biological functions, which were analysed and are partially conserved in a series of mono- and dicotyledonous plant species. The identified biological functions include control over the circadian rhythm, light signalling, cold tolerance, hormone signalling and photoperiodic flowering. The latter function is a central role of GI, as it involves a multitude of pathways, both dependent and independent of the gene CONSTANS(CO) as well as on the basis of interaction with miRNA. The complexity of gene function of GI increases due to the existence of paralogs showing changes in genome structure as well as incidences of sub- and neofunctionalization. We present an updated report of the biological function of GI, integrating late insights into its role in floral initiation, flower development and flower volatile production.

The solute carrier family 25 (SLC25) participates in the transport of metabolites and cofactors across the membranes of mitochondria, plastids, peroxisomes, and endoplasmic reticulum. By calling for genomic blocks involved in adjacent metabolic reactions, this report introduces gene clusters of the Slc25 subfamily 44, stilbene and chalcone synthases, and subunits of the mitochondrial electron transfer complexes. The Slc25A44 gene was found ubiquitously expressed and transcriptionally co-regulated with energy metabolism genes in human, mouse, and Arabidopsis thaliana. The Slc25A44s also had no homozygous missense mutation and were highly conserved at intra-species level with the majority of polymorphism present in the non-coding regions. When expressed in oocytes, AdSlc25A44 from Arachis duranensis showed transport activity for the common precursors of flavonoids, stilbenoids, and ubiquinone. Accordingly, AdSLC25A44 and its human orthologue HsSLC25A44 elevated the production of para-coumaric, 4-aminobenzoic, and 4-hydroxybenzoic acids in Saccharomyces cerevisiae strains designed to produce para-coumaric acid via different pathways. Moreover, the engineered SLC25 subfamily specific signature, i.e., AdSLC25A44^LWW206IQF, had a stronger effect on para-coumaric acid secretion than the native variant. Importantly, the aerobic growth-rate of S. cerevisiae was significantly higher when expressing the AdSLC25A44, HsSLC25A44, or AdSLC25A44^LWW206IQF. These results suggest that SLC25A44 is an essential mitochondrion-ER-nucleus zone transporter associated with metabolism of secondary metabolites and energy.

Today massive amounts of sequenced metagenomic and -transcriptomic data from different ecological niches and environmental locations are available. Scientific progress depends critically on methods that allow extracting useful information from the various types of sequence data. Here, we will first discuss types of information contained in the various flavours of biological sequence data, and how this information can be interpreted to increase our scientific knowledge and understanding. We argue that a mechanistic understanding is required to consistently interpret experimental observations, and that this understanding is greatly facilitated by the generation and analysis of dynamic mathematical models. We conclude that, in order to construct mathematical models and to test mechanistic hypotheses, time-series data is of critical importance. We review diverse techniques to analyse time-series data and discuss various approaches by which time-series of biological sequence data was successfully used to derive and test mechanistic hypotheses. Analysing the bottlenecks of current strategies in the extraction of knowledge and understanding from data, we conclude that combined experimental and theoretical efforts should be implemented as early as possible during the planning phase of individual experiments and scientific research projects.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Here, I introduce a concept called autonomous selection to refer to a source of selection that is part of the individuals upon which it acts. The concept is motivated by a set of phenomena with the following characteristics: Natural selection shaped a variant (e.g., gene, epigenetic mark, or combination thereof) to act in a manner that reduces the frequency of one or more heritable traits of the individual in which it is located if those traits are detrimental to individual or group fitness. Phenomena with these characteristics are peculiar to traditional evolutionary theory but have been identified rather frequently in recent decades. They are also relevant to adaptive evolution: By reducing the frequency of a trait detrimental to fitness, the variant accelerates the evolution of adaptations, which allows its holders to adapt better to constantly changing environments. The variant is shaped by (natural) selection, but also does (autonomous) selection. Several phenomena with these characteristics have been invoked by proponents of the extended evolutionary synthesis (EES). The concept of autonomous selection helps resolve some of the controversy surrounding the EES: EES proponents call attention to the incompleteness of contemporary theory, emphasizing individuals’ processes that influence which adaptations those individuals evolve. I argue for the special importance of individuals’ processes that do not just influence those individuals’ adaptations, but also accelerate the adaptive evolution of those individuals. All known phenomena that fit this description are examples of autonomous selection. Other phenomena raised by EES proponents do not meet this threshold.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Climate change-induced Sea level rise, shoreline changes, and coastal erosion are projected to drive massive population displacement and mobility in Africa. This study was conducted to examine the pattern of shoreline changes, coastal erosion, land use/Land cover dynamics their projections, and its implications on internal migration in Senegal, Kenya and Tanzania representing West and East Africa. The digitized shoreline was mapped into both erosion, accretion and trend analysis which further explains the vulnerability and physical processes that could trigger human displacement within the context of environmental/climate migration. Analysis of landuse and land cover dynamics was obtained from Landsat 5 TM of 1986, Landsat 7 ET of 2006, Landsat 8 OLI/TIRS of 2016 and Landsat 9 OLI/TIRS 2022 and computed using ArcGIS 10.7 for Land-use change and percentage change in square kilometers was conducted to examine landuse/landcover dynamics and their contributions to the risk of coastal erosion in the study regions. The outcome of the shoreline analysis reveals that 972.03sqkm of land has been lost to coastal erosion in Senegal from 1986-2022 with 2016-2022 described as the period with the highest in terms of land loss. In Kenya, -463.30sqkm of land has also been lost to coastal erosion and agents of wave processes with 1986-2006 recording the highest share of -87.74% loss of valuable land while In Tanzania, -1033.35sqkm of valuable land has been lost from 1986-2022 to coastal erosion with 2006-2016 alone recording -10.4634% of land loss. The result of the land use/land cover percentage change analysis indicates a massive loss of vegetation cover with a significant increase in settlement representing urbanization. The scenario modeling of the shoreline on 10,20 and 30ms indicates that 567 persons per sq, 25904.5 persons per sqm and 25904.5 persons per sq km for both 20 and 30ms will be displaced in Senegal while in Kenya 577.5 persons per sq km will be displaced at 10m followed by 1210.3 persons per sq km at 20m and 7737.3 sq km at 30m. In, Tanzania, 702001.9 persons per sq km are projected to be displaced at 10m shift in the shoreline. Structured Questionnaires were administered to elicit responses from coastal dwellers on their perception of coastal erosion and environmental migration as part of ground truthing and the result of the survey affirms that coastal erosion and its exposure are the major drivers of environmental migration in the study area.

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle-foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle-subtalar-foot complex beyond the existing powered ankles.

The work carried out first-principles calculations within the framework of density functional theory to study the structural stability of the CsSnI₃ compound and the influence of phase transitions on their electronic and optical properties. Using the GGA and SCAN functionals, the relaxed structures of the CsSnI₃ phases were obtained and their geometric characteristics were assessed. Using the Phonopy code based on VASP, calculations of phonon and thermodynamic properties were performed, and the temperatures of phase transitions of CsSnI₃ were determined. The temperature dependences of the thermodynamic parameters α-, β-, γ- and δ-phases of CsSnI₃ were analyzed. The trends in free energy, entropy, enthalpy, heat of formation energy and heat capacity were justified in terms of the pattern of changes in the total energy of the four phases of CsSnI₃ from VASP calculations. It is shown that at 0 K the non-perovskite structure of the CsSnI₃ compound (δ-CsSnI₃) is the most stable (followed by γ-CsSnI₃), and the tetragonal phase (β) is quite unstable, having the highest energy among the perovskite phases. It was revealed that at temperatures above 450 K the tetragonal phase becomes stable, and when the temperature drops, it transforms into the cubic phase (α-CsSnI₃). The phase transition between the β and γ phase of perovskite occurs in the range of 300-320 K, and at 320 K a black-yellow transformation of CsSnI₃ occurs in which the cubic phase (black perovskite) undergoes a phase transition to a non-perovskite conformation (yellow phase). The presence of temperature phase transitions between two orthorhombic phases of CsSnI₃ at 360 K was discovered, although direct transitions of the α⟷γ and γ⟷δ types have not yet been reported in any experiment, except for γ→δ transitions under the influence of moisture. Based on well-relaxed structures (from the SCAN calculations), the band gap widths for four CsSnI₃ phases were calculated and compared with experimental measurements. Electronic properties and Fermi level shifts as a result of phase transformations of CsSnI₃ were assessed using the HSE06 functional and machine learning prediction. The values of the complex dielectric constant and the refractive index of all phases of the CsSnI₃ were determined.

Consistent calibration and monitoring is a basic prerequisite for providing reliable time series of global and regional sea level variations from altimetry. The precision of sea level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) is assessed at eleven GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauges readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between gauge and altimetry which improves the agreement between the two data sets by 15-75%. The precision of the altimeters is depending on location and mission and is shown to be at least 1.8 to 3.7 cm based on an assumed precision of 2 cm for the gauges. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by WSV might complement the calibration and monitoring activities at dedicated CalVal stations.

Cloud computing has become a prominent technology due to its important utility service; this service concentrates on outsourcing data to organizations and individual consumers. Cloud computing has considerably changed the manner in which individuals or organizations store, retrieve, and organize their personal information. Despite the manifest development in cloud computing, there are still some concerns regarding the level of security and issues related to adopting cloud computing that prevent users from fully trusting this useful technology. Hence, for the sake of reinforcing the trust between Cloud Clients (CC) and Cloud Service Providers (CSP), as well as safeguarding the CC’s data in the cloud, several security paradigms of cloud computing based on a Third-Party Auditor (TPA) have been introduced. The TPA, as a trusted party, is responsible for checking the integrity of the CC’s data and all the critical information associated with it. However, the TPA could become an adversary and could aim to deteriorate the privacy of the CC’s data by playing a malicious role. In this paper, we present the state-of-art of cloud computing’s privacy-preserving models (PPM) based on a TPA. Three TPA factors of paramount significance have been discussed: TPA involvement, security requirements, and security threats caused by vulnerabilities. Moreover, TPA’s privacy preserving models have been comprehensively analyzed and categorized into different classes with an emphasis on their dynamicity. Finally, we discuss the limitations of the models and present our recommendations for their improvement.

A numerical study for the effect of crest width, breaking parameter and trunk permeability on hydrodynamics and flow behavior in the vicinity of rubble-mound, permeable, zero-freeboard breakwaters (ZFBs) is presented. The modified two dimensional Navier-Stokes equations for two-phase flows in porous media with a Smagorinsky model for the subgrid scale stresses were solved numerically. An immersed-boundary/level-set method was used. The numerical model was validated for the cases of wave propagation over a submerged impermeable trapezoidal bar and over a low-crested permeable breakwater. Five cases of breakwaters were examined, and the main results are: (a) The size of the crest width, B, does not notably affect the wave reflection, vorticity and currents in the seaward region of ZFBs, while wave transmission, currents in the leeward side, and mean overtopping discharge, all decrease with increasing B. A non-monotonic behavior of the wave setup is also observed. (b) As the breaking parameter decreases, wave reflection, transmission, currents, mean overtopping discharge, and wave setup decrease. This observation is also verified by relevant empirical formulas. (c) As the ZFB trunk permeability decreases, an increase of the wave reflection, currents, wave setup, and a decrease of wave transmission and mean overtopping discharge is observed.

Medicago sativa L. (Alfalfa) is a globally recognized forage legume that has recently gained attention for its high protein content, making it suitable for both human and animal consumption. However, due to its perennial nature and autotetraploid genetics, conventional plant breeding requires a longer timeframe compared to other crops. Therefore, genetic engineering offers a faster route for trait modification and improvement. Here, we describe a protocol for achieving efficient transient gene expression in alfalfa through genetic transformation with the Agrobacterium tumefaciens pCAMBIA1304 vector. This vector contains the reporter genes β-glucuronidase (GUS) and green fluorescent protein (GFP), along with a selectable hygromycin B phosphotransferase gene, all driven by the CaMV 35s promoter. Various transformation parameters—such as different explant types, leaf ages, leaf sizes, wounding types, bacterial concentrations (OD600nm), tissue preculture periods, incubation periods, co-cultivation periods, and different concentrations of acetosyringone, silver nitrate, and calcium chloride—were optimized using 3-week-old plantlets raised in vitro. Results were attained from data based on the semi-quantitative observation of the percentage and number of GUS spots on different days of agro-infection in alfalfa explants. The highest percentage (76.2%) of GUS-positive alfalfa leaf explants was observed after 3 days of agroinfection at a bacterial concentration of 0.6, 2 days of preculture, 30 min of infection time, 150 µM acetosyringone, 4 mM calcium chloride, and 75 µM silver nitrate. The transient expression of genes of interest was confirmed via histochemical GUS and GFP assays. The results based on transient reporter gene expression suggest that various factors influence T-DNA delivery in the Agrobacterium-mediated transformation of alfalfa.

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

CRISPR/Cas9 technology is expected to offer novel genome editing-related therapies for various diseases. We previously showed that an adenovirus vector (AdV) possessing eight expression units of multiplex guide RNAs (gRNAs) was obtained with no deletion of these units. Here, we attempted to construct “all-in-one” AdVs possessing expression units of four and eight gRNAs with Cas9 nickase. We expected this to be difficult because extremely high copies of viral genomes during replication may cause severe off-target cleavages of host cells and induce homologous recombination. However, four units in the all-in-one AdV genome were maintained completely intact. For all-in-one AdV containing eight gRNA units, we shortened the U6 promoter of the gRNA expression units and enlarged the E3 deletion in the vector backbone to shorten the AdV genome within the adenovirus packaging limits. The final size of the all-in-one AdV genome containing eight gRNA units still slightly exceeded the reported upper limit. Nevertheless, approximately one-third of the eight units remained intact even upon preparation for in vivo experiments. Although the genome editing efficiency unexpectedly decreased upon enlarging the E3 deletion, our results suggested that all-in-one AdVs containing four and eight intact gRNA units could be obtained if the problems caused by the excessive size of the vector genome are solved.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

Because it can make exact double-strand breaks in DNA, CRISPR-Cas9 can help almost every species and type of cell. It is a powerful way to change the DNA code. CRISPR-Cas9 can be used for a lot more than just changing genes. We are close to being able to do high-throughput gene screening, epigenome editing, in-vivo cell tagging, and RNA change. With the help of CRISPR-Cas9, the function of genes can be studied better, and more realistic disease models can be made. The revolutionary new discipline of gene editing has the potential to profoundly impact healthcare and the life sciences. By simplifying the process of creating double-strand breaks in the DNA of almost any species or kind of cell, CRISPR-Cas9 has revolutionized gene editing. Numerous applications have been found for the CRISPR-Cas9 system. High-throughput gene screening, RNA modification, live-cell chromosome marking, and epigenome editing are all examples. CRISPR-Cas9 facilitates gene research, leading to the development of CRISPR-based disease models. CRISPR-Cas9-based methods of altering the genome will aid researchers in learning more about sickness and discovering better ways to cure it, despite the fact that there are still many questions and large difficulties to answer.

Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, H3K9me3 and H3K27me3 large domains, HiC compartments and lamina associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNAs) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

Methicillin-resistant Staphylococcus aureus (MRSA) exerts a considerable concern in healthcare and the community. Globally MRSA strains cause numerous infections with high morbidity and mortality rates. The success of MRSA is a result of the extensive production of virulence factors. With the limited treatment options for the MRSA infection and growing resistance problem, an urgent call is needed to search for an alternative to antibiotics. One of the promising strategies is targeting the quorum sensing (QS) system, of the MRSA, by using a dendrimer loaded with kinase inhibitor peptide. This study formulates a poly-amidoamine dendrimers (PAMAM) G4 dendrimers loaded with Quorum Quencher (QQ), QQ3 peptide which is a Histidine Kinase inhibitor. The physicochemical properties of the formula were characterized using different in-vitro analysis method such as Zetasizer and transmission electron microscope (TEM). The antibacterial activity and anti-virulence effect of the formula was tested against MRSA and different mutant stains using growth assay, haemolysis assay and biofilm assay. Overall, QQ3-G4 complex showed antibacterial and anti-virulence activity and it can be a potential alternative treatment to overcome antimicrobial resistance and treat MRSA infection.

The rapid advancements in gene therapy have opened up new possibilities for the treatment of genetic disorders, including Duchenne muscular dystrophy, Thalassemia, cystic fibrosis, Hemophilia, and Familial hypercholesterolemia. The utilization of the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases, necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation, while ensuring safety and effectiveness. This review aims to explore the biomedical potential of non-viral vector-explore CRISPR/Cas9 systems for the treatment of genetic diseases. Furthermore, it provides a comprehensive overview of recent research advances in viral and non-viral vector-based gene therapy for genetic disorders, including insights from preclinical and clinical studies. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for the development of novel nano-delivery platforms.

Abstract: Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes were located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes were expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. Hox clusters are irreversibly elongated along the force direction. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can explain this Empirical Rule. In an accidental mutation where the cluster fastening is dismantled, a minimal pulling force can automatically shift the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of temporal collinearity in Drosophila.

The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and miti-gating the burden of this life-threatening disease. This review aims to provide an overview of our current under-standing of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

Chondroitin sulfate (CS) proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is currently under investigation as a marker of cancer malignancy, and as a potential target of anticancer drug treatment. CSPG4 acts as a driver of tumourigenesis by regulating turnover of the extracellular matrix (ECM) to promote tumour cell invasion, migration as well as inflammation and angiogenesis. While CSPG4 has been widely studied in certain malignancies, such as melanoma, evidence is emerging from global gene expression studies, which suggests a role for CSPG4 in squamous cell carcinoma (SCC). While relatively treatable, lack of widely agreed upon diagnostic markers for SCCs is problematic, especially for clinicians managing certain patients, including those who are aged or infirm, as well as those with underlying conditions such as epidermolysis bullosa (EB), for which a delayed diagnosis is likely lethal. In this review, we have discussed the structure of CSPG4, and quantitatively analysed CSPG4 expression in the tissues and pathologies where it has been identified. The aim of this review has been to collate the information available from functional studies and recent transcriptome analysis to determine the usefulness of CSPG4 expression as a diagnostic marker and therapeutic target in management of malignant SCC.

Staphylococcus aureus is a major food-borne pathogen. The ability of S. aureus to produce biofilm is a significant virulence factor triggering its persistence in hostile environments. In this study, we screened a total of 420 different food samples and human hand swabs to detect S. aureus and to determine their biofilm formation ability. Samples analyzed were meat, milk, egg, fish, fast foods, and hand swabs. S. aureus were detected by culturing, staining, biochemical, and PCR. Biofilm formation ability was determined by Congo Red Agar (CRA) plate and Crystal Violet Microtiter Plate (CVMP) tests. The icaA, icaB, icaC, icaD, and bap genes involved in the synthesis of bio-film-forming intracellular adhesion compounds were detected by PCR. About 23.81% (100/420; 95% CI: 14.17-29.98%) samples harbored S. aureus as revealed by detection of the nuc gene. CRA plate revealed 20% of S. aureus isolates as strong biofilm producers, while 69% and 11% as in-termediate and non-biofilm producers, respectively. By the CVMP staining method, 20%, 77%, and 3% of the isolates were found strong, intermediate, and non-biofilm producers. Furthermore, 21% of S. aureus isolates carried at least one biofilm-forming gene, where icaA, icaB, icaC, icaD, and bap genes were detected in 15%, 20%, 7%, 20%, and 10% of the S. aureus isolates, respectively. Bivariate analysis showed high significant correlations (p<0.001) between any of the two adhesion genes of S. aureus isolates. To the best of our knowledge, this is the first study in Bangladesh describing the detection of biofilm-forming S. aureus from foods and hand swabs with molecular-based evidence. Our findings suggest that food samples should be deemed a potential reservoir of biofilm-forming S. aureus that indicates a potential public health significance.

Studies on the influence of dietary components and their effects are fundamental for nutrigenomics, or the study of how nutrients can be cellular sensors, how they affect biological processes and gene expression in different tissues. Lipids are an important source of fatty acids (FA) and energy and are fundamental to biological processes and influence the regulation of transcription. Pigs are excellent model to study nutrigenomics, particularly lipid metabolism because the deposition and composition of FA in their tissues reflect the composition of FA in their diet. Recent studies show that FA supplementation is important in production systems, such as growing and finishing pigs, as it can improve the energy value of the feed, help reduce costs, improve animal welfare, and influence the nutritional value of the meat. Studies show that oleic (OA), linoleic (LA), docosahexaenoic (DHA), and eicosapentaenoic (EPA) acids are associated with the regulation of transcription in tissues such as muscle, liver, adipose tissue, and brain. Other studies indicate that EPA and DHA are associated with changes in specific signaling pathways, altering gene expression and biophysical properties of membranes. This review, therefore, focuses on the current knowledge of the effects of dietary FA on production traits and gene expression.

A technique for fabrication of bacterial cellulose-based films with CeO₂ nanofiller has been developed. The structural and morphological characteristics of the materials have been studied, their thermal and mechanical properties in dry and swollen states having been determined. The preparation methodology makes it possible to obtain composites with a uniform distribution of nanoparticles. The catalytic effect of ceria regarding the thermal oxidative destruction of cellulose has been confirmed by TGA and DTA methods. An increase in CeO₂ content led to an increase in the elastic modulus (a 1.27-fold increase caused by the introduction of 5 wt.% of the nanofiller into the polymer) and strength of the films. This effect is explained by the formation of additional links between polymer macro-chains via the nanoparticles’ surface. The materials fabricated were characterised by a limited ability to swell in water. Swelling caused a 20- to 30-fold reduction in the stiffness of the material, the mechanical properties of the films in a swollen state remaining germane to their practical use. The application of the composite films in cell engineering as substrates for the stem cells’ proliferation has been studied. The increase in CeO₂ content in the films enhanced the proliferative activity of embryonic mouse stem cells. The cells cultured on the scaffold containing 5 wt.% of ceria demonstrated increased cell survival and migration activity. An analysis of gene expression confirmed improved cultivation conditions on CeO₂-containing scaffolds.

Mutual survival among different species of living organisms is quite common in our living world. That mutual survival can produce symbiotic or parasitic relationship among different living organisms. But at the same time, some relationships are harmful to the living organisms creating pathogenic relationships. Why some mutual survivals are beneficial, whereas some relationships are harmful creating different diseases in the living world? That harmful or pathological relationship producing different diseases in both the animal and plant kingdom has been extensively studied by the scientific community several times under the heading of ‘Host-pathogen interaction’ and ‘Disease pathogenesis’. But it is still not clear why some mutual survivals are beneficial or non-harmful, whereas some co-survivals are harmful producing different disease conditions in the living world mainly due to different immune mediated reactions or direct toxic effect of substances produced by an organism. To find the answer to this question, we have to search retrospectively to the evolutionary pattern of our diverse living world. If it is assumed that we have originated from Last Universal Common Ancestor (LUCA) by different cumulative mutations, horizontal gene transfer, mobile genetic elements (MGE), transposition and natural selection, then it would be quite pragmatic to consider that two things were moving side by side in our ancient living world. On one hand it’s purpose was to create the diversification of both unicellular and multi-cellular living world and on the other hand it’s another purpose was to maintain the specific identity of the living organisms. It is the second purpose or the maintenance of specific identity that ultimately led to the development of Immune system.

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN and XBP1). mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.

Multiple mRNA isoforms of the same gene are produced via alternative splicing, a biological mechanism that regulates protein diversity while maintaining genome size. Alternatively spliced mRNA isoforms of the same gene may sometimes have very similar sequence, but they can have significantly diverse effects on cellular function and regulation. The products of alternative splicing have important and diverse functional roles, such as response to environmental stress, regulation of gene expression, human heritable and plant diseases. The mRNA isoforms of the same gene, such as the apoptosis associated CASP3 gene, can have dramatically different functions. The shorter mRNA isoform product CASP3-S inhibits apoptosis, while the longer CASP3-L mRNA isoform promotes apoptosis. Despite the functional importance of mRNA isoforms, very little has been done to annotate their functions. The recent years have however seen the development of several computational methods aimed at predicting mRNA isoform level biological functions. These methods use a wide array of proteo-genomic data to develop machine learning-based mRNA isoform function prediction tools. In this review, we discuss the computational methods developed for predicting the biological function at the individual mRNA isoform level.

Prebiotic oligosaccharides are widely used as human and animal feed additives for their beneficial effects on the gut microbiota. However, there are limited data to assess the direct effect of such functional foods on the transcriptome of intestinal epithelial cells. The purpose of this study is to describe the differential transcriptomes and cellular pathways of colonic cells directly exposed to galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). We have examined the differential gene expression of polarized Caco-2 cells treated with GOS or FOS and their respective mock-treated cells using mRNA sequencing (RNA-seq). A total of 89 significant differentially expressed genes were identified between GOS and mock-treated groups. For FOS treatment, a reduced number of 12 significant genes were observed to be differentially expressed relative to the control group. KEGG and Gene Ontology functional analysis revealed that genes up-regulated in the presence of GOS were involved in digestion and absorption processes, fatty acids and steroids metabolism, potential antimicrobial proteins, energy-dependent and -independent transmembrane trafficking of solutes and amino acids. Using our data, we have established complementary non-prebiotic modes of action for these frequently used dietary fibers.

AbstractIntroduction: Increasing knowledge of obstetric danger signs (ODS) and encouraging birth preparedness and complication readiness (BPCR) practices are strategies to increase skilled maternal health service utilization in low-income countries. One of the methods to increase mothers' knowledge about ODS and promote BPCR practice is through health education intervention (HEI). However, the effect of context-specific community-based health education led by women's groups on these outcomes has not been comprehensively studied, and the existing evidence is inconclusive. Thus, we aimed to evaluate the effect of a context-specific community-based HEI led by women's groups on mothers' knowledge regarding ODS and BPCR practices in southern Ethiopia.Methods: An open-label, two-arm parallel group cluster-randomized controlled trial was conducted from January to August 2023 on pregnant women from 24 clusters (kebeles) (12 interventions and 12 controls) in the northern zone of the Sidama region. The Open Data Kit smartphone application was utilized to collect data. The intention-to-treat analysis was used to compare outcomes between groups. We fitted multi-level mixed-effects modified Poisson regression with robust standard error to account for between and within cluster effects. Results: One thousand and seventy pregnant women (540 in the intervention and 530 in the control clusters) responded to this study, making the overall response rate 95.02%. Excessive vaginal bleeding (94.3% in the interventional group vs. 88.7% in the control group) was the commonest ODS mentioned during childbirth. Overall, 68.7% of women in the intervention group and 36.2% of mothers in the control group had good knowledge of ODS (P-value < 0.001). Saving money and materials (97.1% in the interventional group vs. 92.7% in the control group) was the most frequently practiced BPCR plan. Overall, 64.3% of women in the intervention group and 38.9% of mothers in the control group practiced BPCR (P-value < 0.001). HEI significantly increased overall knowledge of ODS (adjusted risk ratio [ARR]: 1.71; 99% CI: 1.14-2.57) and improved overall BPCR practice (ARR: 1.55; 99% CI: 1.02-2.39). Conclusions: A community-based HEI led by women's groups improved mothers' knowledge regarding ODS and BPCR practices in a rural setting in southern Ethiopia. Interventions designed to increase women's knowledge of ODS and improve BPCR practice must implement context-specific, community-based HEI that aligns with World Health Organization recommendations. Trial registration: NCT05865873

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

High-Level Synthesis (HLS) tools have revolutionized FPGA application development by providing a more efficient and streamlined approach, significantly impacting digital design methodologies. Despite the capability of FPGAs to customize numerical representations in data paths, most HLS projects have focused on fixed-point precision, while floating-point representations remain limited to vendor-provided single, double, and half-precision formats. This paper proposes a customized floating-point library compatible with HLS to address these limitations. This library allows programmers to define the number of exponent and mantissa bits at compile time, providing greater flexibility and enabling the use of mixed precision. Moreover, this library includes optimized implementations of common components such as vector summation (VSUM), dot-product (DP), and matrix-vector multiplication (MVM). Results demonstrate that the proposed library reduces latency and resource utilization compared to vendor IP blocks, particularly in VSUM, DP, and MVM operations. For example, the MVM operation involving a 32x32 matrix, using vendor IP requires 22 clock cycles, whereas CuFP completes the same task in just 7 clock cycles, using approximately 60% fewer DSPs, 10% fewer LUTs, and 60% fewer FFs.

Background: Humoral memory and specific antibodies levels depend on kind of the antigen and individual immunofactors., The presence of IgM antibodies or fourfold rise in specific IgG level, are generally accepted as diagnostic in serology of acute viral infection. This basic model is not adequate for herpesvirome especially after hematopoietic stem cell transplantation (HSCT) due to continuous, usually multifocal antigenic stimulation, various donor serostatus, immunosuppresion and individual immunoreconstitution. Methods: A  case-control study was conducted for identifying cases of Human herpesviruses (HHV) active infection (from 300 diagnosed immunocompromised patients) and evaluating historically associated humoral factors to look at outcomes. We enrolled only patients’ data with meticulous differential diagnosis to exclude other causes, thereby observe pathways and temporal relationships, not statistical ones, usually collected in cohorts. Despite the small number such data collection and analysis avoids a number of biases and indicates cause and effect.Results. In the observational study retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex (HSV) and varicella zoster virus(VZV) reactivation showed a number of biases. In two well differentiated cases (confirmed by Tzanck test) with various disease and conditioning evolution of immunoparameters showed interesting pathway. Exponential decrease of specific IgG after HSCT precedes virus replication with cytopathic effect (shingles, VZV-encephalitis and HSV-induced mucositis). Minima (smallest IgG levels) before herpes virus reactivation were 234,23 mIU/ml and 94 RU/ml for VZV and HSV, respectively. This coincides with low CD4 titer, but without other infectious process. Other immune response parameters such as Treg, cytotoxic T cells, complement and total IgG level were quite the same as before the transplant procedure. Interestingly, the second wave of immunoreconstitution with anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. Patient with lymphocyte depletion in conditioning showed earlier second wave of immunoreconstitution (6th vs 14th month) Conclusions: Typical for infancy kinetics of IgG level is unique after HSCT (the decline phase is first). Host-microbiome factors (i.e. HHV1-3 -serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help to predict the prognosis and improve the management. The lack of differentiation, assessor and confusing bias are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be first to build evidence of a pathway and association between immunoparameters and HHV disease.

Electrification coverage in Sarawak is the lowest at 78.74%, compared to Peninsular Malaysia at 99.62% and Sabah at 82.51%. Kapit, Sarawak with its 88.4% populations located in rural areas and mostly situated along the main riverbanks has great potential to generate electrical energy by hydrokinetic system. Yearly water velocity data is the most significant parameter to perform hydrokinetic analysis study. Nevertheless, the data retrieved from local river databases are inadequate for river energy analysis, thus hindering its progression. Instead, flow rates and rainfall data had been utilised to estimate the water velocity data. This signifies no estimation of water velocity in an unregulated river by using water level data had been made. Therefore, a novel technique of estimating the daily average water velocity data in unregulated rivers is proposed. The modelling of regression equation for water velocity estimation was performed and two regression model equations were generated to estimate both water level and water velocity on-site and proven to be valid as the coefficient of determination values had been R² = 87.4% and R²=87.9%, respectively. The combination of both regression model equations can be used to estimate long-term time series water velocity data for type-C unregulated river in remote areas.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research indicates that they share both distinctive and common pathways. Moreover, they exhibit intriguing intersections with mechanotransduction, a process that involves cells sensing and responding to mechanical forces. This review article describes the intricate interplay between mechanical forces and CI, shedding light on how these forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs) emerge as sensitive players in both CI and the mechanotransduction process. This article presents methods for identifying these TAFs and profiling the associated changes in chromatin structure, offering valuable insights into CI and mechanotransduction regulation. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now known also as a modulator of gene expression. What is important for cancer, is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts the enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NFκB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which have a significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. In general, the capacity of cancer cells to adapt to oxidative stress depends on molecular systems such as the interface of OGG1 with NFκB, which bestows a cancer cell with the molecular mechanism of transformation of its microenvironment to enable adaptation and survival of malignant clones.