Comparison of Genomes of the Hepadnaviridae Family

Background: The Hepadnaviridae family is composed of small hepatotropic DNA viruses, divided into two main genera: Avihepadnavirus, which infects birds;and Orthohepadnavirus, which infects mammals. The human hepatitis B virus (HBV) is a member of the latter family and contains a relaxed circular double-stranded DNA genome of approximately 3 kb, and the objective of this study is to evaluate the genetic diversity of the genome of the Hepadnaviridae family. Materials and Methods: For this study, we evaluated the 26 NCBI reference sequences of the Hepadnaviridae family. Result: The two main genera, Avihepadnavirus and Orthohepadnavirus, show low similarity between them. The Orthohepadnavirus, to which HBV belongs, has two important hosts, monkeys and bats, while the genus, which infects humans, has greater diversity but is similar to the viruses that infect monkeys. The Paraepadnavirus isolated from the white sucker fish and the Herpetohepadnavirus from the Tibetan frog showed strong similarity with the Avihepadnavirus found in birds. The Metahepadnavirus isolated from the bluegill fish was the Hepadnaviridae which had the greatest difference, with less than 20% similarity using CLC Sequence Viewer. Conclusion: The Hepadnaviridae genomic replication cycle involves a late reverse transcriptase (RT) step. This polymerase, however, does not have proofreading activity, resulting in genetic variability in the Hepadnaviridae family.

Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease,and gut microbiota dysbiosis is associated with both of them.AIM To assess the relationship between gut dysbiosis and cardiovascular risk(CVR)in an experimental model of steatohepatitis.METHODS Adult male Sprague-Dawley rats were randomized to a control group(n=10)fed a standard diet and an intervention group(n=10)fed a high-fat choline-deficient diet for 16 wk.Biochemical,molecular,hepatic,and cardiac histopathology.Gut microbiota variables were evaluated.RESULTS The intervention group had a significantly higher atherogenic coefficient,Castelli’s risk index(CRI)-I and CRI-II,interleukin-1β,tissue inhibitor of metalloproteinase-1(all P<0.001),monocyte chemoattractant protein-1(P=0.005),and plasminogen activator inhibitor-1(P=0.037)than the control group.Gene expression of miR-33a increased(P=0.001)and miR-126(P<0.001)decreased in the intervention group.Steatohepatitis with fibrosis was seen in the intervention group,and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance(P=0.007),reduction in the mean area of cardiomyocytes(P=0.037),and an increase of atrophic cardiomyocytes(P=0.007).There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR.The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota(both P<0.001)than controls.Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR.CONCLUSION The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer

The therapeutic efficacy of metformin in prostate cancer(PCa)appears uncertain based on various clinical trials.Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation,which leads to drug resistance.However,the underlying mechanism is still unclear.In this study,we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation.Super-enhancers(SEs),crucial regulatory elements,have been shown to be associated with drug resistance in various cancers.Our analysis of SEs in metformin-resistant(MetR)PCa cells revealed a correlation with Prostaglandin Reductase 1(PTGR1)expression,which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing.Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases,resulting in reduced sensitivity to metformin.Additionally,we identified key transcription factors that significantly increase PTGR1 expression,such as SRF and RUNX3,providing potential new targets to address metformin resistance in PCa.In conclusion,our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis,offering potential avenues to enhance metformin’s therapeutic efficacy in PCa.

Polygalacturonase-inhibiting proteins as an exogenously applied natural solution for prevention of postharvest fungal infections

Polygalacturonase inhibiting proteins(PGIPs)are plant proteins involved in the inhibition of polygalacturonases(PGs),cell-wall degrading enzymes often secreted by phytopathogenic fungi.Previously,we confirmed that PGIP2 from Phaseolus vulgaris(PvPGIP2)can inhibit the growth of Aspergillus niger and Botrytis cinerea on agar plate.In this study,we further validated the feasibility of using PGIP as an environmental and ecological friendly agent to prevent fungal infection post-harvest.We found that application of either purified PGIP(full length PvPGIP2 or truncated tPvPGIP2_5-8),or PGIP-secreting Saccharomyces cerevisiae strains can effectively inhibit fungal growth and necrotic lesions on tobacco leaf.We also examined the effective amount and thermostability of PGIP when applied on plants.A concentration of 0.75 mg/mL or higher can significantly reduce the area of B.cinerea lesions.The activity of full-length PvPGIPs is not affected after incubation at various temperatures ranging from20 to 42◦C for 24 h,while truncated tPvPGIP2_5-8 lost some efficacy after incubation at 42◦C.Furthermore,we have also examined the efficacy of PGIP on tomato fruit.When the purified PvPGIP2 proteins were applied to tomato fruit inoculated with B.cinerea at a concentration of roughly 1.0 mg/mL,disease inci-dence and area of disease had reduced by more than half compared to the controls without PGIP treatment.This study explores the potential of PGIPs as exogenously applied,eco-friendly fungal control agents on fruit and vegetables post-harvest.

From filaments to function: The role of the plant actin cytoskeleton in pathogen perception,signaling and immunity

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.

Exploring transposable element-based markers to identify allelic variations underlying agronomic traits in rice

Transposable elements(TEs)are a major force in the production of new alleles during domestication;nevertheless,their use in association studies has been limited because of their complexity.We have developed a TE genotyping pipeline(TEmarker)and applied it to whole-genome genome-wide association study(GWAS)data from 176 Oryza sativa subsp.japonica accessions to identify genetic elements associated with specific agronomic traits.TE markers recovered a large proportion(69%)of single-nucleotide polymorphism(SNP)-based GWAS peaks,and these TE peaks retained ca.25%of the SNPs.The use of TEs in GWASs may reduce false positives associated with linkage disequilibrium(LD)among SNP markers.A genome scan revealed positive selection on TEs associated with agronomic traits.We found several cases of insertion and deletion variants that potentially resulted from the direct action of TEs,including an allele of LOC_Os11g08410 associated with plant height and panicle length traits.Together,these findings reveal the utility of TE markers for connecting genotype to phenotype and suggest a potential role for TEs in influencing phenotypic variations in rice that impact agronomic traits.

Future directions for screening and treatment in congenital hearing loss

Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt identification and individualized therapies.Diagnosing hearing loss in newborns is challenging,especially in mild or progressive cases,and its management requires a multidisciplinary team of healthcare providers comprising audiologists,pediatricians,otolaryngologists,and genetic counselors.While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before,a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality.In this review,we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.

The potential of plant proteins as antifungal agents for agricultural applications

Fungal pathogens induce a variety of diseases in both plants and post-harvest food crops,resulting in significant crop losses for the agricultural industry.Although the usage of chemical-based fungicides is the most common way to control these diseases,they damage the environment,have the potential to harm human and animal life,and may lead to resistant fungal strains.Accordingly,there is an urgent need for diverse and effective agricultural fungicides that are environmentally-and eco-friendly.Plants have evolved various mechanisms in their innate immune system to defend against fungal pathogens,including soluble proteins secreted from plants with antifungal activities.These proteins can inhibit fungal growth and infection through a variety of mechanisms while exhibiting diverse functionality in addition to antifungal activity.In this mini review,we summarize and discuss the potential of using plant antifungal proteins for future agricultural applications from the perspective of bioengineering and biotechnology.

A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity

Upon initiation at a start codon,the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins.While some sequence elements are able to trigger programmed ribosomal frameshifing(PRF),very little is known about how the ribosome normally prevents spontaneous frameshif errors that can have dire consequences if uncorrected.Using high resolution ribosome profling data sets,we discovered that the translating ribosome uses the 3�end of 18S rRNA to scan the AUG-like codons afer the decoding process.Te postdecoding mRNA:rRNA interaction not only contributes to predominant translational pausing,but also provides a retrospective mechanism to safeguard the ribosome in the correct reading frame.Partially eliminating the AUG-like“sticky”codons in the reporter message leads to increased+1 frameshif errors.Remarkably,mutating the highly conserved CAU triplet of 18S rRNA globally changes the codon“stickiness”.Further supporting the role of“sticky”sequences in reading frame maintenance,the codon composition of open reading frames is highly optimized across eukaryotic genomes.Tese results suggest an important layer of information embedded within the protein-coding sequences that instructs the ribosome to ensure reading frame fdelity during translation.

Neotropical electric fishes(Gymnotiformes)as model organisms for bioassays

Electric fishes(Gymnotiformes)inhabit Central and South America and form a relatively large group with more than 200 species.Besides a taxonomic challenge due to their still unresolved systematic,wide distribution and the variety of habitats they occupy,these fishes have been intensively studied due to their peculiar use of bioelectricity for electrolocation and communication.Conventional analysis of cells,tissues and organs have been complemented with the studies on the electric organ discharges of these fishes.This review compiles the results of 13 bioassays developed during the last 50 years,which used the quickness,low costs and functionality of the bioelectric data collection of Gymnotiformes to evaluate the effects of environmental contaminants and neuroactive drugs.