Abstract:

Background:Gastrointestinal tract cancers account for approximately one-third of cancer-related deaths. Early diagnosis and effective treatment are the most important ways to prevent cancer-related morbidity and mortality. ROMO1 has been shown to play an important role in many types of cancer. However, the biological function of ROMO1 is still poorly understood in gastrointestinal system cancers. The aim of this study is to reveal the expression change and oncogenic role of ROMO in gastrointestinal system cancers. Methods:Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, TIMER, GeneMANIA, TISIDB and STRING were applied to assess the biological function of ROMO1 in gastrointestinal cancers (Colon adenocarcinoma (COAD), Esophageal carcinoma (ESCA), Liver hepatocellular carcinoma (LIHC), Pancreatic adenocarcinoma (PAAD), and Stomach adenocarcinoma (STAD)). Results:ROMO1 is significantly increased in gastrointestinal cancers and overexpression of ROMO1 was associated with clinicopathological features. In addition, ROMO1 has been found to be closely associated with between tumor-infiltrating immune cells in gastrointestinal cancers. ROMO1 is closely related to the inner mitochondrial membrane proteins (TIMM) family. Conclusison: The study revealed that ROMO1 is of significant clinical importance for gastrointestinal cancers and may have potential clinical utility in treatment and prognosis.

Abstract:

We investigated whether microalgae or linseed supply during the early postpartum period affects ovarian restimulation and supports the first postpartum ovulation in lactating anovulatory goats. Thirty-eight An-glo-Nubian-crossbred adult goats were allocated into three groups: con-trol diet (n=12), fed a total mixed ration (TMR) comprising chopped elephant grass and concentrate; algal diet (n=13), fed TMR+green microalgae (1% dry matter); and linseed diet (n=13), TMR+linseed (12% dry matter). Supplements were furnished from the 2nd to 5th week (time of weaning). Goats were estrus synchronized on day 40 by insertion of an intravaginal CIDR device for 5 days, after which 0.075mg PGF2α was applied to in-duce ovulation, and estrus was monitored for 72 hours. From the 5th-15th day of ovulation induction, the corpus luteum (CL) area and progesterone rate were monitored. The algal and linseed groups showed lower feed intake (P<0.001) and higher (P<0.001) triglyceride levels/follicle numbers, respectively. After estrus induction, no differences were ob-served in estrus response; however, the linseed group showed more and larger growing follicles (P=0.016 and P<0.01), a higher ovulation rate (P<0.05), larger CL area (P<0.05), and higher progesterone levels (P<0.001). Linseed after delivery stimulates follicular growth before and after ovulation induction, favoring better CL quality during the first ovulation.

Abstract: Clinical reasoning is an essential competence of veterinary graduands. Unfortunately, clinical reasoning and, therefore, the quality of provided veterinary medical services, are prone to bias, difficulties, and errors. Literature on biases, difficulties, and errors in clinical reasoning in veterinary medical education is scarce or focused on theoretical rather than practical application. In this review, we address the practicality of learning and teaching biases, difficulties, and errors in clinical reasoning to veterinary learners utilizing a practical example of a cow with a prolapsed uterus, complicated by hypocalcemia and hypomagnesemia. Learners should be guided through all of the stages of clinical reasoning as much as possible under direct supervision. The common clinical biases, difficulties, or errors in veterinary medical encounters may differ between stages of development of the learner, with more difficulties occurring in earlier stages (Observer, Reporter, ± Interpreter) but more heuristic biases occurring at later stages (Manager, Educator, ± Interpreter). However, clinical errors may occur at any learner development stage. Therefore, remediation of clinical biases, difficulties, and errors in veterinary medical encounters should use strategies that are tailored to the level of development of the learner, but also to the specific encounter (e.g., client, patient, and context).

Abstract:

Molecular biology is undergoing a transformative evolution through the integration of Artificial Intelligence (AI) and bioinformatics, which collectively empower researchers to analyze complex genomic datasets, uncover hidden patterns in genetic information, and advance the paradigm of precision medicine. Notable breakthroughs include AlphaFold’s revolutionary contribution to protein structure prediction, achieving near-experimental accuracy, and PolyPhen’s role in assessing the functional impact of genetic mutations, advancing precision diagnostics. These advancements demonstrate the potential of AI to accelerate discoveries in functional genomics and disease prediction models. However, the integration of these technologies also raises significant ethical concerns. For instance, issues related to genetic privacy have become increasingly critical, as the misuse of sensitive genomic data could lead to discrimination in healthcare and employment. This comprehensive review explores the dynamic intersection of AI and bioinformatics, emphasizing their roles in gene-disease association studies, protein structure prediction, and functional genomics. It also critically addresses challenges, including data quality issues, computational limitations, and the ethical implications of genetic privacy. Future research directions focus on enhancing AI model transparency, overcoming computational barriers, and developing robust ethical frameworks to ensure equitable benefits in clinical and research settings. By integrating cutting-edge AI technologies, such as explainable AI (XAI) and federated learning, with robust bioinformatics methodologies, this review highlights a roadmap for revolutionizing genetic research and fostering advancements in personalized medicine.

Abstract: Although the stifle joint of wild felines shares several characteristics observed in domestic cats, others are specific to each species. This study aimed to evaluate the stifle joints of eight Puma concolor, including two young and six adults, through different imaging examinations. All stifles were assessed using radiographs and computed tomography (CT). Magnetic resonance imaging (MRI) was performed on the stifles of one animal using 7 Tesla equipment. In all imaging modalities, the four sesamoid bones were detected. Meniscal mineralization was identified in the stifles of three adult animals and one young animal. The cruciate ligaments and menisci were identified on CT, with MRI providing better visualization. The mean values of CT measurements (cm2) in the sagittal section included patella (2.475), medial fabella (0.481), lateral fabella (0.772), popliteal sesamoid (0.222), and medial meniscus (0.051). No differences were found in HU values between the central trabecular bone of the patella and popliteal sesamoid, cortical bone of the patella and lateral and medial fabellas, or cortical bone of the patella and popliteal sesamoid. In conclusion, the descriptions of the stifle of Puma concolor in the different imaging methods contribute to understanding the species and can serve as a basis for identifying alterations.

Abstract: Aronia, haskap, and goji berries are characterized by their high content of bioactive compounds and their beneficial health properties, as well as their resistance to harsh agronomic conditions. In this work, cultivars of these species growing in a mountainous region of central-western Spain were characterized by analyzing physicochemical parameters and bioactive compounds. Goji fruits showed the highest TSS content and the lowest acidity values. The sugar profile suggested that goji cultivars will have a higher sweetness due to higher fructose and glucose content. However, aronia cultivars will be the least sweet due to their high sorbitol content. The total organic acid content was much higher in aronia and haskap than in goji fruits, and the profile varied according to species. The total phenolic content was significantly higher in aronia fruits. A total of 15 phenolic compounds were detected with anthocyanins being predominant in aronia and haskap berries, however, they were not detected in goji fruits. Nevertheless, carotenoid compounds were found in goji berries, and non-detected in aronia and haskap fruits. Aronia fruits showed the highest antioxidant capacity compared to haskap and goji fruits. The PCA analysis allowed us to classify the samples and determine which parameters have the greatest influence.

Abstract: The Promyelocytic Leukemia protein (PML) and its associated nuclear bodies have recently emerged as critical regulators of embryonic stem (ES) cell identity. Despite their recognized importance, the complete spectrum of PML-mediated molecular events in ES cells remains unclear. In this report we have studied how PML is shaping the proteomic and SUMO proteomic landscape in ES cells. Proteomic profiling of PML-depleted ES cells uncovered a downregulation of self-renewal factors and an upregulation of proteins associated with translation and proteasomal activity, reflecting a cellular transition from pluripotency to differentiation. Importantly, PML promotes the sumoylation of pluripotency-related factors, chromatin organizers and cell cycle regulators. We identify SALL1 and CDCA8 as novel PML-directed sumoylation targets, both critical for ES cell maintenance. SALL1 sumoylation increases the activation of the Wnt pathway, contributing to its ability to inhibit ES cell differentiation. Similarly, CDCA8 sumoylation enhances its capacity to promote cell proliferation. Collectively, our findings demonstrate that PML regulates ES cell identity by modulating the abundance or sumoylation of key regulators involved in pluripotency and cell cycle progression.

Abstract: Ubiquitylation is a post-translational modification that modulates protein function and stability. It is orchestrated by the concerted action of three types of enzymes, with substrate specificity governed by ubiquitin ligases (E3s), which may exist as single proteins or as part of multi-protein complexes. Although Cullin (CUL) proteins lack intrinsic enzymatic activity, they participate in the formation of active ubiquitin ligase complexes, known as Cullin-Ring ubiquitin Ligases (CRLs), through their association with ROC1 or ROC2, along with substrate adaptor and receptor proteins. Mammalian genomes encode several CUL proteins (CUL1-9), each contributing to distinct CRLs. Among these CUL proteins, CUL1, CUL3, and CUL4 are believed to be the most ancient and evolutionarily conserved from yeast to mammals, with CUL4 uniquely duplicated in vertebrates. Genetic evidence strongly implicates CUL4-based ubiquitin ligases (CRL4s) in chromatin regulation across various species and suggests that in vertebrates, CRL4s have also acquired a cytosolic role, facilitated by a cytosol-localizing paralog of CUL4. Substrates identified through biochemical studies have elucidated the molecular mechanisms by which CRL4s regulate chromatin and cytosolic processes. The substantial body of knowledge on CUL4 biology amassed over the past two decades provides a unique opportunity to explore the functional evolution of CRL4. In this review, we synthesize the available structural, genetic, and biochemical data on CRL4 from various model organisms and discuss the conserved and novel functions of CRL4s.

Abstract: Cryptococcus neoformans is an opportunistic fungal pathogen that is a continuous global health concern especially for immunocompromised populations. The World Health Organization recognized C. neoformans as one of four critical fungal pathogens, thus emphasizing the need for increased research efforts and clinical resource expansion. Currently there are no fungal vaccines available for clinical use. Exciting new findings in cryptococcal vaccine development have identified whole cell-based and subunit-based vaccinations to help mitigate health risks and make commercialization attainable. Importantly, recent work has focused on how different cryptococcal cell wall antigens modified in these vaccine candidates allow us to manipulate their immunogenicity to produce a desired long term protective anti-fungal immune response. In this review we discuss the different cryptococcal cell immunogens, namely the polysaccharide capsule, glucans, chitin/chitosan, mannoproteins, and extracellular vesicles and their role in novel cryptococcal vaccination approaches. Additionally, we examine the immunological mechanisms responsible for protection in these vaccine candidates and the similar host response stimulation pathways induced through different immunogen exposure.

Abstract:

Pattern separation has been studied in relation to both the retrieval and encoding processesis considered a crucial process that allow humans to store and remember allows us to distinguish among the highly similar items. Within this body of research,and overlapping experiences which constitute our episodic memory. Not only different episodes share common features, but it is often the role of case that they share the context in which those similar items are found becomes highly relevant. One hypothesis assertsthey occurred. While there has been a great number of studies investigating pattern separation, and its behavioural counterpart, a process known as mnemonic discrimination, surprisingly, research exploring the influence of context on pattern separation or mnemonic discrimination has been less common. The available evidence showed that similar items with similar context leadled to a failure in pattern separation due to high similarity that triggers overlap between events. In contrast, another hypothesis statesOn the other hand, others have shown that pattern separation can take place even under these conditions, allowing humans to distinguish between events with similar items and contexts, as different hippocampal subfields would play complementary roles in enabling both pattern separation and pattern completion. In the present study, we were interested in testing how stability in context influenced pattern separation. WeDespite the fact that pattern separation is by definition an encoding computation the existing literature has focused on the retrieval phase. Here, we used a subsequent memory paradigm in which we manipulated the similarity of context during encoding. We of visual objects selected from diverse categories. Thus, we manipulated the encoded context of each object category (four items within a category), so that some categories had the same intercategory context (same context) and others had different intercategory contexts (different context).context. This approach allowed us to test not only the items presented, but also include the conditions that entail the greatest demand on pattern separation. After a 20-minute period, participants performed a visual mnemonic discrimination task in which they had to differentiate between old, similar, and new items by providing one of the three options for each item tested. According item. Similarly to the second hypothesis describedprevious studies, we found no interaction between judgments and contexts, and participants were able to discriminate between old and lure items at the behavioural level in both conditions. Moreover, when averaging the ERPs of all the items presented within a category, a significant SME emerged between hits and new misses, but not between hits and old false alarms or similar false alarms. These results suggest that item recognition emerges from the interaction with subsequently encoded information, and not just between item memory strength and retrieval processes.