Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2 and its relation to other viruses, protein sequences from sarbecoviruses were analyzed to identify conserved inserts or deletions (termed CSIs) demarcating either particular clusters/lineages of sarbecoviruses or those shared by specific lineages shedding light on their interrelationships. We report several clade-specific CSIs in the spike (S) and nucleocapsid (N) proteins that reliably demarcate distinct sarbecoviruses clades providing important insights into the origin and evolution of SARS-CoV-2. Two CSIs in the N-terminal domain (NTD) of S-protein are uniquely shared by SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r cluster); another CSI supports a closer relationship of SARS-CoV-2 to BatCov-RaTG13. Three additional CSIs in the NTD are specific for two Bat-SARS-like CoVs (viz. CoVZXC21 and CoVZC45; CoVZC cluster) which form an outgroup of the SARS-CoV-2r cluster. Interestingly, one of the pangolin-CoV-MP789 also shares these CSIs but lack the CSIs specific for the SARS-CoV-2r cluster. The N-terminal sequence (aa 1-320) of the S-protein for pangolin-CoV-MP789 shows highest similarity (85.94%) to the CoVZC cluster, while its C-terminal region including the receptor binding domain (RBD) is most similar (97-98% identity) to the SARS-CoV-2 virus. These observations indicate that the spike protein sequence for the strain MP789 is of chimeric origin. Multiple CSIs described here also distinguish two bat SARS-CoVs strains (BM48-31/BGR/2008 and SARS_BtKY72) from all others. Our work also clarifies that two large CSIs (5 aa and 13 aa) found in the RBD of S-protein are mainly specific for the SARS and SARS-CoV-2r clusters of CoVs. The surface loops formed by these CSIs are predicted to be important in the binding of S-protein with the human ACE-2 receptor. Lastly, we have mapped the locations of different CSIs in the structure of the S-protein. These studies reveal that the three CSIs specific for the SARS-CoV-2r cluster form distinct surface-exposed loops/patches on the S-protein. As the surface-exposed loops play important roles in mediating novel interactions, the novel lobes/patches formed by the SARS-CoV-2-specific CSIs in the spike protein are predicted to play important roles in the interaction of this protein with other surface-exposed components in the host cells thereby enhancing the binding/infectivity of this virus to humans.

In our recent publications pertaining to 4G model of final unification and based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. Considering this kind of approach, nuclear structure can be understood in terms of strong and weak interactions and cold nuclear fusion like complicated concepts can be understood in a theoretical approach positively. In this paper, by considering the accountability of we are making an attempt to improve the applicability and effectiveness of SEWMF. Number 0.00125 being a workable electroweak coefficient for Z=6 to 132 and A=2Z to 3.5Z, number of free nucleons assumed to be associated with electroweak interaction can be expressed as Improved asymmetry term can be expressed as, where represents the light house like stable mass number. With reference to old version, our improved binding energy formula can be expressed as, We are working on its possible modification for mass numbers less than the stable mass numbers. Following this approach, it is possible to show that nuclear binding energy scheme is associated with strong and weak interactions and is practically independent of Coulombic repulsions. Proceeding further, currently believed cold nuclear fusion assumed be associated with hydrated metals can be understood and can be confirmed with strong and weak interactions independent of coulombic repulsions. We are very confident to say that our approach will certainly motivate modern science community in this new direction.

The transition from the Peptide/RNA world to the Protein/RNA world in the hydrothermal vent environment was a major event in the history of life. The advent of proteins utterly changed the conditions of emerging life, representing a watershed in its development. During subsequent translation various protein enzymes emerged driving protocells into a more complex and interconnected system. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Four major events followed after availability of various kinds of protein molecules during prebiotic synthesis. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) the beginnings of the virus world; and (4) the advent of DNA. The first innovation mediated by proteins was the improvement of the cell membrane. The phospholipid membrane was initially evolved in a vent environment from the gradual modification of a fatty acid membrane via an intermediate phosphatidate acid by non-enzymatic reactions. The phospholipid is then synthesized from phosphatidate acid by a series of enzymes. To make the phospholipid membrane more permeable, various protein molecules interacted with the cell membrane. Proteins not only stabilized the wall membrane, but also acted as pumps, preventing some molecules from the protocells from crossing the membrane barriers, while permitting other selected molecules and ions to enter and leave the protocell. The second modification led by proteins is the gradual conversion of the interior of the protocell from a water-like medium into a gel-like cytoplasm, which became the storehouse of a wide range of biomolecules including amino acids, proteins, nucleic acids, ribosomes, as well as salt and water. The third innovation utilizing the newly synthesized proteins was the emergence of the ancient virus world. In the milieu of different kinds of mRNAs in the prebiotic soup, jelly-roll capsid genes originated de novo within genomes of nonviral mRNAs by overprinting. These fragile capsid genes were possibly coated by proteins on the mineral substrate for stability and durability, transforming them into ancient viral particles. These protein coats were random and were not encoded by encased genes. Some protocells might have engulfed these viral particles, when the capsid genes utilized the ribosomes of the host to translate into the appropriate capsid proteins. These capsid proteins then coated the viral genes to make new copies of primordial viruses inside the protocell. Since then, viruses became capsid-encoding organisms. These primordial mRNA viruses parasitized RNA-based protocells, manipulating them to make new copies of themselves. This was the beginning of a relentless war between viruses and their protocellular hosts. The next stage in viral evolution was the emergence of a primitive retrovirus (pre-retrovirus) with a new kind of replicative strategy in a sense that it could turn its RNA into DNA using its own reverse transcriptase enzyme. This is the beginning of the Retro world that facilitated the transition from RNA to DNA genomes. The infection of RNA protocells with pre-retroviruses progressively transferred the RNA genome to a viral DNA genome by retro-transcription. The advent of DNA by the pre-retrovirus marks the fourth innovation, when a number of enzymes had already developed and were utilized by pre-retroviruses. With continued infection, DNA viruses slowly transferred not only their core replication enzymes, such as helicase, primase, and DNA polymerase, to RNA protocells, but also to their DNAs as well. Thus, began the DNA world, when DNA replaced RNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. The new protocell with the DNA genome will diversify into large populations of DNA protocells that will outcompete populations of RNA protocells. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. It was carried out by a set of enzymes that formed a Z-ring at the site of replication. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification. These primordial hyperthermophiles, presumably the first life, obtained food and energy directly from the vent environment. However, such a situation was self-limiting, so the early cells evolved their own mechanisms for generating metabolic energy and synthesizing the molecules necessary for their reproduction. The earliest fossil record (≥ 3.5 Ga) of biotic activity is preserved in the Archean hydrothermal and sedimentary rocks of the Nuvvuagittuq Craton of Canada, the Isua Craton of Greenland, the Pilbara Craton of Australia, the Kaapvaal Craton of South Africa, and the Singhbhum Craton of India in the form of the carbonaceous remains of microbial cells, cellular microfossils, and stromatolites. These microscopic fossils provide crucial evidence of the origin and early evolution of prokaryotic cells, beginning with hyperthermophiles. Molecular phylogenetic analysis suggests that both domains of life ¬– Bacteria and Archaea probably split from the last universal common ancestor (LUCA), a hyperthermophilic organism. In the younger sequences of these Archean cratons, two kinds of photosynthetic bacteria, anoxygenic green sulfur bacteria, and oxygenic cyanobacteria, appeared in quick succession from the thermophilic ancestor, indicating a shift of niche from a benthic to a planktonic, with reduced thermotolerance. The development of anoxygenic and oxygenic photosynthesis would have allowed life to escape the hydrothermal setting and invade a newly evolved habitat—broad continental shelves to tap solar energy. Cyanobacteria invaded the global ocean, turned it into blue and green, produced oxygen for the first time, and left their signatures in the carbonates and stromatolites.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

The emergence of proteins in the prebiotic world was a watershed event at the origin of life. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Five major biochemical innovations followed in succession after availability of various kinds of protein molecules during decoding and translation of mRNAs. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) primitive gene regulation; (4) the beginnings of the virus world; and (5) the advent of DNA. The creative role of viruses during prebiotic synthesis led to the origin of the DNA world, when DNA replaced mRNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification by mutation. The habitat of the earliest fossil record (≥ 3.5 Ga) from the Archean sedimentary rocks of Canada, Greenland, Australia, South Africa, and India offers a new window on the early radiation of microbial life. The development of anoxygenic and then oxygenic photosynthesis from early hyperthermophiles would have allowed life to escape the hydrothermal setting to the mesophilic global ocean.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

Aquaculture is rapidly becoming one of the pivotal sectors in the farm economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge – the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement of vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia, TiLV, salmon anemia, vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host-pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

We delve into nonrelativistic quantum electrodynamics within a background magnetic field, ensuring gauge invariance via a vector potential. Our exploration extends to the Lagrangian, which incorporates electron self-interactions and electromagnetic field interactions. Through the path integral formalism, we elucidate the effective action, with a specific focus on the photon propagator and screening effects. Examining density and current components reveals Laurent expansions in the hydrodynamic limit. The equations of motion in real space are derived, leading to discussions on phenomena such as Poiseuille-like flow and the Navier-Stokes equation. To ground our theoretical framework at practical contexts, we consider applications such as the fluid dynamics at binary star systems. Depending on the velocity of the expelled fluid, our analysis allows for both nonrelativistic and relativistic treatments, providing a versatile tool for understanding the intricacies of fluid behavior at astrophysical scenarios. Additionally, we recognize that at the presence of a magnetic field, magnetohydrodynamics becomes crucial. While our current focus is at nonrelativistic quantum electrodynamics, the insights gained here contribute to a broader understanding, offering a comprehensive foundation for quantum electrodynamics analysis at diverse physical systems.

Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, chromosome fragments may not be restored correctly. Resulting chromosome rearrangements can become critical breast cancer drivers. Because I had data from thousands of cancer structural alterations that matched viral infections, I wondered whether infections contribute to chromosome breaks and rearrangements in hereditary breast cancers. There are currently no interventions to prevent chromosome breaks because they are thought to be unavoidable. However, if chromosome breaks come from infections, they can be treated or prevented. I used bioinformatic analyses to test publicly available breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had the strongest matches to Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Many breakpoints were near sites that anchor EBV genomes, human EBV tumor-like sequences, EBV-associated epigenetic marks, and fragile sites. On chromosome 2, sequences near EBV genome anchor sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences. Five EBV genome anchor sites were near breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Breakpoint flanking regions resembled known EBV-cancers. Twenty-five breakpoints in breast cancers were within 1.25% of EBV cancer breakpoints. In addition to BRCA1 or BRCA2 mutations, all the breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can activate and produce nucleases that break chromosomes. Alternatively, anchored viral episomes can obstruct break repairs, whatever the cause. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.