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Biology subjects

Zhu, Z.

Publications and source records attributed to Zhu, Z..

At least 307 records · Page 17Linked to original sources

Ecological network inferred from field data elucidates invasion of a freshwater ecosystem by the exotic silver carp

BackgroundAccurate network models of species interaction could be used to predict population dynamics and be applied to manage real world ecosystems. Most relevant models are nonlinear, however, and data available from real world ecosystems are too noisy and sparsely sampled for common inference approaches. Here we improved the inference of generalized Lotka-Volterra (gLV) ecological networks by using a new optimization algorithm to constrain parameter signs with prior knowledge and a perturbation-based ensemble method. ResultsWe applied the new inference to long-term species abundance data from the freshwater fish community in the Illinois River, United States. We constructed an ensemble of 668 gLV models that explained 79% of the data on average. The models indicated (at a 70% level of confidence) a strong positive interaction from emerald shiner (Notropis atherinoides) to channel catfish (Ictalurus punctatus), which we could validate using data from a nearby observation site, and predicted that the relative abundances of most fish species will continue to fluctuate temporally and concordantly in the near future. The network shows that the invasive silver carp (Hypophthalmichthys molitrix) has much stronger impacts on native predators than on prey, supporting the notion that the invader perturbs the native food chain by replacing the diets of predators. ConclusionsEnsemble approaches constrained by prior knowledge can improve inference and produce networks from noisy and sparsely sampled time series data to fill knowledge gaps on real world ecosystems. Such network models could aid efforts to conserve ecosystems such as the Illinois River, which is threatened by the invasion of the silver carp.

ecology↗

ASFVdb: an integrative resource of African swine fever for genomics and proteomics analysis

The recent outbreaks of African swine fever (ASF) in China and Europe have threatened the swine industry globally. To control the transmission of the African swine fever virus (ASFV), we developed ASFVdb, the African swine fever virus database, an online data visualization and analysis platform for comparative genomics and proteomics. On the basis of known ASFV genes, ASFVdb reannotates the genomes of every strain and annotates 4833 possible ORFs. Moreover, ASFVdb performs a thorough analysis of the population genetics of all the published genomes of ASFV strains and performs functional and structural predictions for all genes. For each ASFV gene, visitors can obtain not only basic information of the gene but also the distribution of the gene in strains, conserved or high mutation regions, possible subcellular location of the gene and topology of the gene. In the genome browser, ASFVdb provides sliding window population genetics analysis results, which facilitate genetics and evolutional analyses at the genomic level. The web interface is constructed based on SWAV 1.0. ASFVdb is freely accessible at http://asfvdb.popgenetics.net.

bioinformatics↗

FALCONET: an R package to accelerate automatic visualisation of genome scale metabolic models

SummaryFALCONET (FAst visuaLisation of COmputational NETworks) enables the automatic for-mation and visualisation of metabolic maps from genome-scale models with R and CellDesigner, readily facilitating the visualisation of multi-layers omics datasets in the context of metabolic networks.\n\nMotivationUntil now, numerous GEMs have been reconstructed and used as scaffolds to conduct integrative omics analysis and in silico strain design. Due to the large network size of GEMs, it is challenging to produce and visualize these networks as metabolic maps for further in-depth analyses.\n\nResultsHere, we presented the R package - FALCONET, which facilitates drawing and visualizing metabolic maps in an automatic manner. This package will benefit the research community by allowing a wider use of GEMs in systems biology.\n\nAvailability and implementationFALCONET is available on https://github.com/SysBioChalmers/FALCONET and released under the MIT License.\n\nContactnielsenj@chalmers.se\n\nSupplementary informationSupplementary data are available online.

systems biology↗

Transcription of a plasticity gene is activated by neuronal hyperpolarization

Long term synaptic plasticity requires transcriptional changes in response to neuronal activity. While neuronal activity rapidly increases transcription of activity-regulated genes, it is less clear how neurons respond to neuronal inactivity. The plasticity gene Pura encodes a Rho1 GEF whose rhythmic expression drives 24 hour rhythms in the retraction of the projections of Drosophila LNv circadian pacemaker neurons. We found that Pura transcription in LNvs is repressed by neuronal activity and induced by neuronal inactivity - the opposite of canonical activity-regulated genes. We identified the Pax6 transcription factor Toy as the relevant activator of Pura transcription, and found that toy transcription itself is induced by neuronal inactivity and by reducing intracellular calcium. Thus we propose that neurons contain complementary gene expression programs that are activated by either increased or decreased neuronal activity.

neuroscience↗

Verify Hub Genes of expression profile in aortic dissection

BackgroundTo assess the mRNAs expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD). Methodology: mRNA microarray expression signatures of TAD tissues (n=6) and no TAD tissues (NT;n=6) were analyzed by Arraystar human mRNAs microarray. Real-time PCR (qRT-PCR) were used to validate the result of mRNAs microarray. Bioinformatic tools including gene ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis were utilized. The protein-protein interaction networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytohubba analysis were used to infer the most hug gene and pathways. Results: The top 10 hub genes CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG,CXCL12 and ASPM were identified from the PPI network. Module analysis revealed that TAD was associated with cell cycle, oocyte meiosis, p53 signaling pathway, progesterone-mediated oocyte maturation. The qRT-PCR result showed that the expression of all hug genes was significantly increased in TAD samples (p < 0.05). Conclusions: These candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.\n\nAuthor summaryMany basic characteristics underlying the establishment of aortic dissection have not been studied in detail. The presented work sought to understand the pathogenesis of human thoracic aortic dissection by employing bioinformatic tools to explore the hub mRNAs and potential molecular mechanisms of thoracic aortic dissection. Many pathway were thought to have relevant with this disease, but the most important pathway was not define. We used bio-mathematical analysis to explore the potential functions in thoracic aortic dissection and identified the hub genes and explored the intrinsic molecular mechanisms involved in thoracic aortic dissection between two microarray analysis. Finally, we indentified the cell cycle maybe the key pathway in thoracic aortic dissection.

bioinformatics↗

Conditional GWAS analysis identifies putative disorder-specific SNPs for psychiatric disorders

Substantial genetic liability is shared across psychiatric disorders but less is known about risk variants that are specific to a given disorder. We used multi-trait conditional and joint analysis (mtCOJO) to adjust GWAS summary statistics of one disorder for the effects of genetically correlated traits to identify putative disorder-specific SNP associations. We applied mtCOJO to summary statistics for five psychiatric disorders from the Psychiatric Genomics Consortium - schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit hyperactivity disorder (ADHD) and autism (AUT). Most genom-wide significant variants for these disorders had evidence of pleiotropy (i.e., impact on multiple psychiatric disorders) and hence have reduced mtCOJO conditional effect sizes. However, subsets of genome-wide significant variants had larger conditional effect sizes consistent with disorder-specific effects: 15 of 130 genome-wide significant variants for schizophrenia, 5 of 40 for major depression, 3 of 11 for ADHD and 1 of 2 for autism. In addition, we identified a number of variants that approached genome-wide significance in the original GWAS and have larger conditional effect sizes after conditioning on the other disorders. We show that decreased expression of VPS29 in the brain may increase risk to SCZ only and increased expression of CSE1L is associated with SCZ and MD, but not with BIP. Likewise, decreased expression of PCDHA7 in the brain is linked to increased risk of MD but decreased risk of SCZ and BIP.

genetics↗

GWAS of 19,629 individuals identifies novel genetic variants for regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits

Volumetric variations of human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) and post-GWAS analyses of 101 brain volumetric phenotypes using the UK Biobank (UKB) sample including 19,629 participants. GWAS identified 287 independent SNPs exceeding genome-wide significance threshold of 4.9*10-10, adjusted for testing multiple phenotypes. Gene-based association study found 142 associated genes (113 new) and functional gene mapping analysis linked 122 more genes. Many of the discovered genetic variants have previously been implicated with cognitive and mental health traits (such as cognitive performance, education, mental disease/disorders), and significant genetic correlations were detected for 29 pairs of traits. The significant SNPs discovered in the UKB sample were supported by a joint analysis with other four independent studies (total sample size 2,192), and we performed a meta-analysis of five samples to provide GWAS summary statistics with sample size larger than 20,000. Using genome-wide polygenic risk scores prediction, up to 4.36% of phenotypic variance (p-value=2.97*10-22) in the four independent studies can be explained by the UKB GWAS results. In conclusion, our study identifies many new genetic variants at SNP, locus and gene levels and advances our understanding of the pleiotropy and genetic co-architecture between brain volumes and other traits.

genetics↗

Comparative genome analysis of 12 Shigella sonnei strains: virulence, resistance, and their interactions

Shigellosis is a highly infectious disease that are mainly transmitted via faecal-oral contact of the bacteria Shigella. Four species have been identified in Shigella genus, among which S. flexneri is used to be the most prevalent species globally and commonly isolated from developing countries. However, it is being replaced by S. sonnei that is currently the main causative agent for dysentery pandemic in many emerging industrialized countries such as Asia and the Middle East with unclear reasons. For a better understanding of S. sonnei virulence and antibiotic resistance, we sequenced 12 clinical S. sonnei strains with varied antibiotic-resistance profiles collected from four cities in Jiangsu Province, China. Phylogenomic analysis clustered antibiotic sensitive and resistant S. sonnei into two distinct groups while pangenome analysis reveals the presence and absence of featured genes in each group. Screening of 31 classes of virulence factors found out that type 2 secretion system is doubled in resistant strains. Further principle component analysis based on the interactions between virulence and resistance indicated that abundant virulence factors are associated with higher resistant phenotypes. The result present here is based on statistical analysis of a small sample size and serves basically as a guidance for further experimental and theoretical studies.

microbiology↗

Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells

Zika virus (ZIKV), an emerging flavivirus which causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barre syndrome, continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of ribonucleoside analogues. Here, we synthesized and tested a library of 13 ProTides against ZIKV in human neural stem cells. Strong activity was observed for 2'-C-methyluridine and 2'-C-ethynyluridine ProTides with an aryloxyl phosphoramidate masking group. Conversion of the aryloxyl phosphoramidate ProTide group of 2'-C-methyluridine to a 2-(methylthio)ethyl phosphoramidate completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2'-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic effect, while the former compounds triphosphate active metabolite was better incorporated by purified ZIKV NS5 polymerase over time. Molecular superpositioning revealed different orientations of residues opposite the 2'-fluoro group of sofosbuvir. These findings suggest both a nucleobase and ProTide group bias for the anti-ZIKV activity of nucleoside analogue ProTides in a disease-relevant cell model.

microbiology↗

Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

genomics↗

Rice annexin OsANN4 interacting with OsCDPK24, reduces root aerenchyma formation by modulating H2O2 under ABA treatment

Plant annexins are calcium- and lipid-binding proteins that have multiple functions, and a significant amount of research on plant annexins has been reported in recent years. However, the functions of annexins in diverse biological processes in rice are largely unclear. Herein, we report that OsANN4, a calcium-binding rice annexin protein, is a substrate for OsCDPK24, and the OsANN4 phosphorylation site is the 13th serine, which is a key site for phosphorylation. Most strikingly, abscisic acid (ABA) promotes the interaction between OsANN4 and OsCDPK24. Moreover, knocking down OsANN4 by RNA interference resulted in visible and invisible phenotypes with exogenous ABA treatment, such as shorter shoots of seedlings, less lateral roots, earlier root aerenchyma formation and so on. The further analyzed results showed that decreased superoxide dismutase (SOD) and catalase (CAT) activity of the RNAi lines, which control H2O2 accumulation for redox homeostasis, and further promoted earlier aerenchyma formation of the root. These results suggest that a proposed molecular mechanism exists between OsANN4 and H2O2 production to response ABA.\n\nHighlightOsANN4 enhances SOD and CAT activities to scavenge H2O2 to alleviate the formation of aerenchyma under ABA treatment. OsCDPK24 interacts with and phosphorylates OsANN4, this interaction strengthened under ABA treatment.

plant biology↗

MATRIEX Imaging: Multi-Area Two-photon Real-time In-vivo Explorer

Two-photon laser scanning microscopy, originally developed since 1990s1, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo2. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel multi-axis optical conjugation method that enables two-photon imaging at single-cell resolution simultaneously in multiple areas at different depths, each of which could have a view diameter of ~200 m and could be largely freely targeted within a zone up to 12-mm diameter. For example, we show simultaneous imaging of neuronal activities in the primary visual cortex (V1), the primary motor cortex (M1) and the hippocampal CA1 region of awake mice. This method can be readily implemented on a single conventional two-photon microscope to enable multi-area exploration of neuronal activities in vivo.

neuroscience↗

Metagenomic unmapped reads provide important insights into human microbiota and disease associations

We developed a computational pipeline, MicroPro, for metagenomic data analyses that take into account all the reads from known and unknown microbial organisms and for associating viruses with complex diseases. We utilized MicroPro to analyze metagenomics data related to three diseases: colorectal cancer, type-2 diabetes and liver cirrhosis, and showed that including reads from unknown organisms will markedly increase the prediction accuracy of the disease status based on metagenomics data. We identified new microbial organisms associated with these diseases. Viruses were shown to play important roles in colorectal cancer and liver cirrhosis, but not in type-2 diabetes. MicroPro is available at https://github.com/zifanzhu/MicroPro.

bioinformatics↗

A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control

We investigated afferent inputs from all areas in the frontal cortex (FC) to different subregions in the rostral anterior cingulate cortex (rACC). Using retrograde tracing in macaque monkeys, we quantified projection strength by counting retrogradely labeled cells in each FC area. The projection from different FC regions varied across injection sites in strength, following different spatial patterns. Importantly, a site at the rostral end of the cingulate sulcus stood out as having strong inputs from many areas in diverse FC regions. Moreover, it was at the integrative conjunction of three projection trends across sites. This site marks a connectional hub inside the rACC that integrates FC inputs across functional modalities. Tractography with monkey diffusion magnetic resonance imaging (dMRI) located a similar hub region comparable to the tracing result. Applying the same tractography method to human dMRI data, we demonstrated that a similar hub can be located in the human rACC.

neuroscience↗

Mechanism of action of methotrexate against Zika virus

Zika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barre syndrome, reemerged as a serious public health threat in Latin America in recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), which is clinically used as an anti-cancer chemotherapy and anti-rheumatoid agent. We studied the mechanism of action of MTX against ZIKV in relation to its inhibition of dihydrofolate reductase (DHFR) in vitro using Vero and human neural stem cells (hNSCs). As expected, an antiviral effect for MTX against ZIKV was observed, showing up to ten-fold decrease in virus titer during MTX treatment. We also observed that addition of leucovorin (a downstream metabolite of DHFR pathway) rescued the ZIKV replication impaired by MTX treatment in ZIKV-infected cells, explaining the antiviral effect of MTX through inhibition of DHFR. We also found that addition of adenosine to ZIKV-infected cells was able to rescue ZIKV replication inhibited by MTX, suggesting that restriction of de novo synthesis adenosine triphosphate (ATP) pools suppresses viral replication. These results confirm that the DFHR pathway can be targeted to inhibit replication of ZIKV, similar to other published results showing this effect in related flaviviruses.

microbiology↗

Landscape of RNA editing reveals new insights into the dynamic gene regulation of spermatogenesis based on integrated RNA-Seq

Spermatogenesis is an important physiological process associated with male infertility. But whether there are RNA editings (REs) and whats the role of REs during the process are still unclear. In this study, we integrated published RNA-Seq datasets and established a landscape of REs during the development of mouse spermatogenesis. 7530 editing sites among all types of male germ cells were found, which enrich on some regions of chromosome, including chromosome 17 and both ends of chromosome Y. Totally, REs occur in 2012 genes during spermatogenesis, more than half of which harbor at two different sites of the same gene at least. We also found REs mainly occur in introns, coding regions (CDSs) and intergenic regions. Moreover, about half of the REs in CDSs can cause amino acids changes. Finally, based on our adult male Kunming mice, we verified that there is a non-synonymous A-to-I RNA editing site in Cog3 during spermatogenesis, which is conserved not only between species but also across tissues. In short, based on the power of integrating RNA-Seq datasets, we provided the landscape of REs and found their dynamic changes during mouse spermatogenesis. This research strategy is general for other types of sequencing datasets and biological problems.

developmental biology↗

The role of glycaemic, lipid, blood pressure and obesity risk factors as mediators of the effect of height on Coronary Artery Disease and Type 2 Diabetes Mellitus: A Mendelian Randomisation Study.

We investigated by Mendelian Randomisation (MR) analyses the causal effect of adult height on coronary artery disease (CAD) (23,755 cases, 425,339 controls) and type 2 diabetes (T2D) (29,427 cases, 416,908 controls) in UK Biobank. We then examined whether such effects are mediated via known cardiometabolic risk factors including body mass index (BMI), glycaemic traits, lipid levels and blood pressure. We further cross-checked our findings by two-sample MR and Multivariate MR analyses with publicly available summary statistics data. One standard deviation (SD) higher genetically determined height (~6.5 cm) was causally associated with a 14% decrease in CAD risk (OR= 0.86, 95% CI= 0.790.94). This causal association remained significant after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk appeared to be independent of risk factors such as lipid levels, blood pressure and BMI; association was reduced by only 1-3% after adjustment for potential mediators. We observed no direct causal effect of height on T2D risk, once its effect on BMI was taken into account (OR= 0.99, 95% CI= 0.96-1.02), suggesting that BMI acts as a mediator.

genetics↗

Homologous recombination shapes the genetic diversity and drives the evolution of African swine fever viruses

Recent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.

microbiology↗