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Biology subjects

Zhang, B.

Publications and source records attributed to Zhang, B..

At least 19 recordsLinked to original sources

Probability cueing of singleton-distractor locations in visual search: priority-map- or dimension-based inhibition?

Observers can learn the likely locations of salient distractors in visual search, reducing their potential to capture attention (Ferrante et al., 2018; Sauter et al., 2018a; Wang & Theeuwes, 2018a). While there is agreement that this involves positional suppression of the likely distractor location(s), it is contentious at which stage of search guidance the suppression operates: the supra-dimensional priority map or feature-contrast signals within the distractor dimension. On the latter account, advocated by Sauter et al., target processing should be unaffected by distractor suppression when the target is defined in a different (non-suppressed) dimension to the target. At odds with this, Wang and Theeuwes found strong suppression not only of the (color) distractor, but also of the (shape) target when it appeared at the likely distractor location. Adopting their paradigm, the present study ruled out that increased cross-trial inhibition of the single frequent (frequently inhibited) as compared to any of the rare (rarely inhibited) distractor locations is responsible for this target-location effect. However, a reduced likelihood of the target appearing at the frequent vs. a rare distractor location contributes to this effect: removing this negative bias abolished the cost to target processing with increasing practice, indicative of a transition from priority-map- to dimension-based - and thus a flexible locus of - distractor suppression.\n\nPublic Significance StatementDistraction by a salient visual stimulus outside the focus of the task at hand occurs frequently. The present study examined whether and how knowledge of the likely location(s) where the distractors occur helps the observer to mitigate distraction. The results confirmed that observers can learn to suppress distracting stimuli at likely locations. Further, they showed that, the suppression may occur at different levels in the hierarchically organized visual system where the priorities of which objects to be attended in the environment are determined.

neuroscience

BIN1 genetic risk factor for Alzheimer is sufficient to induce early structural tract alterations in entorhinal cortex-dentate gyrus pathway and related hippocampal multi-scale impairments

Genetic factors are known to contribute to Late Onset Alzheimers disease (LOAD) but their contribution to pathophysiology, specially to prodomic phases accessible to therapeutic approaches are far to be understood. To translate genetic risk of Alzheimers disease (AD) into mechanistic insight, we generated transgenic mouse lines that express a [~]195 kbp human BAC that includes only BIN1, a gene associated to LOAD. This model gives a modest BIN1 overexpression, dependent of the number of BAC copies. At 6 months of age, we detected impaired entorhinal cortex (EC)-hippocampal pathways with specific impairments in EC-dentate gyrus synaptic long-term potentiation, dendritic spines of granular cells and recognition episodic memory. Structural changes were quantified using MRI. Their whole-brain functional impact were analyzed using resting state fMRI with a hypoconnectivity centered on entorhinal cortex. These early phenotype defects independent of any changes in A-beta can be instrumental in the search for new AD drug targets.

neuroscience

Proteomic Profile of TGF-β1 treated Lung Fibroblasts identifies Novel Markers of Activated Fibroblasts in the Silica Exposed Rat Lung

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-{beta}1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-{beta}1 treatment and 196 proteins were expressed at [≥] 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-{beta}1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-{beta}1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-{beta}1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.\n\nHighlightsWe identified 196 proteins differentially expressed between control and TGF-{beta}1 treated fibroblastsby LC-MS/MS.\n\nSeveral proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2\n\nKnockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.

pharmacology and toxicology

ProTargetMiner: A proteome signature library of anticancer molecules for functional discovery

We present a publicly available, expandable proteome signature library of anticancer molecules in A549 adenocarcinoma cells. Based on 287 proteomes affected by 56 drugs, the main dataset contains 7,328 proteins and 1,307,859 refined protein-drug pairs. By employing the specificity concept in partial least square modeling, deconvolution of drug targets and mechanistic proteins is achieved for most compounds, including some kinase inhibitors. We built the first protein co-regulation database that takes into account both protein expression and degradation. A surprising number of strong anti-correlations is found, underscoring the importance of protein repression in cell regulation. Our analysis uncovered a group of proteins with extremely steady expression which are likely essential for core cellular functions. These findings bring about deeper understanding of cell mechanics. Extension of the dataset to novel compounds will facilitate drug design. The introduced specificity concept and modeling scheme are beneficial in other analysis types as well.\n\nStatement of SignificanceProTargetMiner is the first of its kind library of proteome responses of human cancer cells to anticancer molecules. This expandable resource facilitates the deconvolution of drug targets, action mechanisms, and cellular effects. It reveals death modalities, uncovers protein co-regulation and anti-correlation networks and defines the \"untouchable\" proteome essential for core cellular functionalities.

cell biology

Genome-wide identification and expression specificity analysis of the DNA methyltransferase gene family under adversity stresses in cotton

DNA methylation is an important epigenetic mode of genomic DNA modification that is an important part of maintaining epigenetic content and regulating gene expression. DNA methyltransferases (MTases) are the key enzymes in the process of DNA methylation. Thus far, there has been no systematic analysis the DNA MTases found in cotton. In this study, the whole genome of cotton C5-Mtase coding genes was identified and analyzed using a bioinformatics method based on information from the cotton genome. In this study, 51 DNA MTase genes were identified, of which 8 belonged to G. raimondii (group D), 9 belonged to G. arboretum L. (group A), 16 belonged to G. hirsutum L. (group AD1) and 18 belonged to G. barbadebse L. (group AD2). Systematic evolutionary analysis divided the 51 genes into four subfamilies, including 7 MET homologous proteins, 25 CMT homologous proteins, 14 DRM homologous proteins and 5 DNMT2 homologous proteins. Further studies showed that the DNA MTases in cotton were more phylogenetically conserved. The comparison of their protein domains showed that the C-terminal functional domain of the 51 proteins had six conserved motifs involved in methylation modification, indicating that the protein has a basic catalytic methylation function and the difference in the N-terminal regulatory domains of the 51 proteins divided the proteins into four classes, MET, CMT, DRM and DNMT2, in which DNMT2 lacks an N-terminal regulatory domain. Gene expression in cotton is not the same under different stress treatments. Different expression patterns of DNA MTases show the functional diversity of the cotton DNA methyltransferase gene family. VIGS silenced Gossypium hirsutum l. in the cotton seedling of DNMT2 family gene GhDMT6, after stress treatment the growth condition was better than the control. The distribution of DNA MTases varies among cotton species. Different DNA MTase family members have different genetic structures, and the expression level changes with different stresses, showing tissue specificity. Under salt and drought stress, G. hirsutum L. TM-1 increased the number of genes more than G. raimondii and G. arboreum L. Shixiya 1. The resistance of Gossypium hirsutum L.TM-1 to cold, drought and salt stress was increased after the plants were silenced with GhDMT6 gene.

genomics

Hydroxymethylated-P16 Allele Is Transcription-Inactive

Background5-Methylcytosine can be oxidized into 5-hydroxymethylcytosine (5hmC) in the genome. Methylated-P16 (P16M) can be oxidized into completely hydroxymethylated-P16 (P16H) in human cancer and precancer cells. The aim of this study is to investigate the biological function of P16H.\n\nMethodsTrue P16M and P16H were analyzed using bisulfite/TAB-based assays. A ZFP-based P16-specific dioxygenase (P16-TET) was constructed and used to induce P16H. Cell proliferation and migration were determined with a series of biological analyses.\n\nResults(A) The 5hmCs were enriched in the antisense-strand of the P16 exon-1 in HCT116 and AGS cells containing methylated-P16 alleles (P16M). (B) P16-TET induced both P16H and P16 demethylation in H1299 and AGS cells and reactivated P16 expression. Notably, P16H was only detectable in the sorted P16-TET H1299 and AGS cells that did not show P16 expression. (C) P16-TET significantly inhibited the xenograft growth derived from H1299 cells in NOD-SCID mice, but did not inhibit the growth of P16-deleted A549 control cells. P16-siRNA knockdown could rescue P16-TET-inhibited cell migration.\n\nConclusionHydroxymethylated P16 alleles are transcriptionally inactive.\n\nAUTHOR SUMMARYIt is well known that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidations, a certain proportion of 5hmCs remain in the genome. Although it is supposed that occurrence of 5hmCs may contribute to the flexibility of chromatin and the protection of the bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In the present study, we engineered a zinc-finger protein-based P16-specific DNA dioxygenase and used it to induce P16 hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that the hydroxymethylated P16 alleles retain transcriptionally inactive. This is supported by our recent findings that mRNAs are always transcribed only from the unmethylated P16 strands, but not from the hydroxymethylated/methylated strands in HCT116 cells, and that the risks for malignant transformation are similar for patients with the P16 methylation-positive oral epithelial dysplasia with and without P16 hydroxymethylation in a prospective study.

molecular biology

Zfp189 Mediates Stress Resilience Through a CREB-Regulated Transcriptional Network in Prefrontal Cortex

Stress resilience involves numerous brain-wide transcriptional changes. Determining the organization and orchestration of these transcriptional events may reveal novel antidepressant targets, but this remains unexplored. Here, we characterize the resilient transcriptome with co-expression analysis and identify a single transcriptionally-active uniquely-resilient gene network. Zfp189, a previously unstudied zinc finger protein, is the top network key driver and its overexpression in prefrontal cortical (PFC) neurons preferentially activates this network, alters neuronal activity and promotes behavioral resilience. CREB, which binds Zfp189, is the top upstream regulator of this network. To probe CREB-Zfp189 interactions as a network regulatory mechanism, we employ CRISPR-mediated locus-specific transcriptional reprogramming to direct CREB selectively to the Zfp189 promoter. This single molecular interaction in PFC neurons recapitulates the pro-resilient Zfp189-dependent downstream effects on gene network activity, electrophysiology and behavior. These findings reveal an essential role for Zfp189 and a CREB-Zfp189 regulatory axis in mediating a central transcriptional network of resilience.

neuroscience

Effects of P16 DNA Methylation on Proliferation, Senescence, and Lifespan of Human Fibroblasts

The aim is to study the effects of P16 DNA methylation on lifespan of normal cells. An expression-controllable pTRIPZ vector expressing P26-specific zinc finger binding protein-based methyltransferase (P16-Dnmt) was used to induce P16 methylation in primary CCD-I8C0 fibroblasts via stable transfection. Long-term dynamic IncuCyte analysis showed that CCD-I8C0 fibroblasts expressing baseline P16-Dnmt continued proliferating until passage-26 in the 53th post-transfection week, while vector control cells stopped proliferating at passage-6 and completely died 2 weeks later. The proliferation rate of baseline P16-Dnmt cells was significantly higher than that of vector control cells. The proportion of P-galactosidase-positive staining cells was significantly decreased in baseline P16-Dnmt cells compared to vector control cells. The P16 expression was lost in baseline P16-Dnmt cells at and after passage-6. The average telomere length in baseline P16-Dnmt cells also gradually decreased. In conclusion, P16 methylation could prevent senescence, promote proliferation, and expand lifespan of human fibroblasts, which may play a role in cancer development.\n\nSummaryA zinc finger protein-based DNA methyltransferase (P16-Dnmt) expressed at the baseline level could specifically methylate P16 promoter CpG islands. P16 methylation induced by baseline P16-Dnmt could significantly prevent senescence, promote proliferation, and expand lifespan of primary human fibroblasts.

cell biology

PRL-1 is required for neuroprotection against olfactory CO2 stimulation in Drosophila

The Mammalian phosphatase of regenerating liver (PRL) family is primarily recognized for its oncogenic properties. Here we found that in Drosophila, loss of prl-1 resulted in CO2-induced brain disorder presented as irreversible wing hold up with enhancement of Ca2+ responses at the neuron synaptic terminals. Overexpression of Prl-1 in the nervous system could rescue the mutant phenotype. We show that Prl-1 is particularly expressed in CO2-responsive neural circuit and the higher brain centers. Ablation of the CO2 olfactory receptor, Gr21a, suppressed the mutant phenotype, suggesting that CO2 acts as a neuropathological substrate in absence of Prl-1. Further studies found that the wing hold up is an obvious consequence upon knockdown of Uex, a magnesium transporter, which directly interacts with Prl-1. Conditional expression of Uex in the nervous system could rescue the phenotype of prl-1 mutants. We demonstrate that Uex acts genetically downstream of Prl-1. Our findings provide important insights into mechanisms of Prl-1 protection against olfactory CO2 stimulation induced brain disorder at the level of detailed neural circuits and functional molecular connections.

neuroscience

Pan-cancer analysis of RNA binding proteins (RBPs) reveals the involvement of the core pre-mRNA splicing and translation machinery in tumorigenesis

RNA binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, transport, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression and regulatory mechanisms in human cancer has not been well characterized. Here, we analyzed mRNA expression of 1487 RBPs in ~6700 clinical samples across 16 human cancer types and found that there were significantly more upregulated RBPs than downregulated ones in tumors when compared to their adjacent normal tissues. Across almost all of the 16 cancer types, 109 RBPs were consistently upregulated (cuRBPs) while only 41 RBPs were consistently downregulated (cdRBPs). Integrating expression with the copy number and DNA methylation data, we found that the overexpression of cuRBPs is largely associated with the amplification of copy number, whereas the downregulation of cdRBPs may be a result of epigenetic silencing mediated by DNA methylation. Furthermore, our results indicated that cuRBPs could work together to promote cancer progression potentially through the involvement of splicing and translation machinery, while cdRBPs might function independently to suppress tumorigenesis. Additionally, we focused on colon cancer and identified several novel potential oncogenic RBPs, such as PABPC1L which might promote cancer development via regulating the core splicing machinery. In summary, we showed distinct expression landscapes, regulatory mechanisms and characteristics of cuRBPs and cdRBPs and implicated several novel RBPs in cancer pathogenesis. Moreover, our results suggest that the involvement of the core pre-mRNA splicing and translation machinery could be critical in tumorigenesis.

systems biology

The probiotic effectiveness in experimental colitis is correlated with gut microbiome and host genetic features

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, as a proof-of-concept, we utilized Bifidobacterium longum JDM 301, a widely used commercial probiotic strain in China, to study potential factors that may influence the beneficial effect of probiotics in experimental colitis. We found that the probiotic therapeutic effect was varied across individual mouse even with the same genetic background and consuming the same type of food. The different probiotic efficacy was highly correlated with different microbiome features in each mouse. Consumption of a diet rich in fat can change the host sensitivity to mucosal injury-induced colitis but did not change the host responsiveness to probiotic therapy. Finally, the host genetic factor TLR2 was required for a therapeutic effect of B. longum JDM 301. Together, our results suggest that personalized microbiome and genetic features may modify the probiotic therapeutic effect.

microbiology

Proteomic Analysis of ACE Inhibitory Peptides extracted from Fermented Goat Milk

Protein extracted from goat milk was hydrolyzed with LH (Lactobacillus Helveticus-cicc22171). Angiotensin Converting Enzyme (ACE) inhibitory peptides were purified from fermented samples of goat milk protein with LH by optimizing incubation time to 8 hours (S-8), 16 hours (S-16), 24 hours (S-24) and 36 hours (S-36), via ultrafiltration. Molecular weight cut-off; 10000 Da (PM-10) membrane was used to perform size exclusion chromatography. Sample with 24 h incubation time was considered as best hydrolyzed as compared to others, by applying Nin-Hydrin reaction and SDS-PAGE analysis. ACE inhibitory assay validated the authenticity of S-24 in inhibiting ACE, in vitro. Furthermore, Q executive Hybrid Quadrapole-Orbitrap Mass Spectrometry was used to determine molecular structure and amino acid sequence of ACE inhibitory peptides. Two protein groups VLPVPQKAVPQ and VLPVPQKVVPQ containing PVP, VVP along with one most abundant peptide TQTPVVVPPFLQPEIMGVPKVKE containing VPP has been identified with highest ACE inhibitory activity on the basis of intensity, small structure and higher concentration of hydrophobic and aromatic amino acids. Fermented goat milk containing these novel bioactive peptides, can be used as nutraceuticals to inhibit ACE and control hypertension.

microbiology

Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment at 2, 4 and 6h in vitro. In vivo, twenty-four male Sprague-Dawley rats were randomly divided into four groups (model group: no blocking of hilum in the left lung; control group: blocking of hilum in the left lung for 1h with DMSO lavage; 3-MA group: blocking of hilum in the left lung for 1h with 100ml/kg of 3-MA (5mol/L) solution lavage; rapamycin group: blocking of hilum in the left lung for 1h with 100ml/kg of rapamycin (250nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the NF-{kappa}B signaling pathway, restrained the expression of pro-inflammatory factors. A contrary result was confirmed by 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stage of hypoxia in vitro and in vivo. This could be a new protective method for lung ischemia-reperfusion injury.

cell biology

A novel approach of human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases

A key goal of geroscience research is to discover effective interventions to extend human healthspan, the years of healthy life. Currently, majority of the geroprotectors are found by testing compounds in model organisms; whether these compounds will be effective in humans is largely unknown. Here we present a novel strategy called ANDRU (aging network based drug discovery) to help the discovery of human geroprotectors. Instead of relying on model organisms, this approach is driven by human genomic and pharmacogenomic data. It first identifies human aging subnetworks that putatively function at the interface between aging and age-related diseases; it then screens for pharmacological or genetic interventions that may \"reverse\" the age-associated transcriptional changes seen in these subnetworks. We applied ANDRU to human adipose and artery tissues. In adipose tissue, PTPN1, a target for diabetes treatment and APOE, a known genetic factor for human longevity and diseases like Alzheimers disease, were ranked at the top. For small molecules, conjugated linoleic acid and metformin, a drug commonly used to treat type 2 diabetes, were ranked among the top compounds. In artery tissue, N-methyl-D-aspartate antagonists and curcumin were ranked at the top. In summary, ANDRU represents a promising human data-driven strategy that may speed up the discovery of interventions to extend human healthspan.

systems biology

MS-PyCloud: An open-source, cloud computing-based pipeline for LC-MS/MS data analysis

Rapid development and wide adoption of mass spectrometry-based proteomics technologies have empowered scientists to study proteins and their modifications in complex samples on a large scale. This progress has also created unprecedented challenges for individual labs to store, manage and analyze proteomics data, both in the cost for proprietary software and high-performance computing, and the long processing time that discourages on-the-fly changes of data processing settings required in explorative and discovery analysis. We developed an open-source, cloud computing-based pipeline, MS-PyCloud, with graphical user interface (GUI) support, for LC-MS/MS data analysis. The major components of this pipeline include data file integrity validation, MS/MS database search for spectral assignment, false discovery rate estimation, protein inference, determination of protein post-translation modifications, and quantitation of specific (modified) peptides and proteins. To ensure the transparency and reproducibility of data analysis, MS-PyCloud includes open source software tools with comprehensive testing and versioning for spectrum assignments. Leveraging public cloud computing infrastructure via Amazon Web Services (AWS), MS-PyCloud scales seamlessly based on analysis demand to achieve fast and efficient performance. Application of the pipeline to the analysis of large-scale iTRAQ/TMT LC-MS/MS data sets demonstrated the effectiveness and high performance of MS-PyCloud. The software can be downloaded at: https://bitbucket.org/mschnau/ms-pycloud/downloads/

bioinformatics

Intercellular signaling network underlies biological time across multiple temporal scales

MotivationCellular, physiological and molecular processes must be organized and regulated across multiple time domains throughout the lifespan of an organism. The technological revolution in molecular biology has led to the identification of numerous genes implicated in the regulation of diverse temporal biological processes. However, it is natural to question whether there is an underlying regulatory network governing multiple timescales simultaneously.\n\nResultsUsing queries of relevant databases and literature searches, a single dense multiscale temporal regulatory network was identified involving core sets of genes that regulate circadian, cell cycle, and aging processes. The network was highly enriched for genes involved in signal transduction (P = 1.82e-82), with p53 and its regulators such as p300 and CREB binding protein forming key hubs, but also for genes involved in metabolism (P = 6.07e-127) and cellular response to stress (P = 1.56e-93). These results suggest an intertwined molecular signaling network that affects biological time across multiple temporal scales in response to environmental stimuli and available resources.\n\nContactjoshua.millstein@usc.edu\n\nSupplementary informationSupplementary data are available online.

systems biology

Structural survey of HIV-1-neutralizing antibodies targeting Env trimer delineates epitope categories and suggests vaccine templates

HIV-1 broadly neutralizing antibodies are desired for their therapeutic potential and as templates for vaccine design. Such antibodies target the HIV-1-envelope (Env) trimer, which is shielded from immune recognition by extraordinary glycosylation and sequence variability. Recognition by broadly neutralizing antibodies thus provides insight into how antibody can bypass these immune-evasion mechanisms. Remarkably, antibodies neutralizing >25% of HIV-1 strains have now been identified that recognize all major exposed surfaces of the prefusion-closed Env trimer. Here we analyzed all 206 broadly neutralizing antibody-HIV-1 Env complexes in the PDB with resolution suitable to define their interaction chemistries. These segregated into 20 antibody classes based on ontogeny and recognition, and into 6 epitope categories (V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide, and subunit interface) based on recognized Env residues. We measured antibody neutralization on a 208-isolate panel and analyzed features of paratope and B cell ontogeny. The number of protruding loops, CDR H3 length, and level of somatic hypermutation for broadly HIV-1 neutralizing antibodies were significantly higher than for a comparison set of non-HIV-1 antibodies. For epitope, the number of independent sequence segments was higher (P < 0.0001), as well as the glycan component surface area (P = 0.0005). Based on B cell ontogeny, paratope, and breadth, the CD4-binding site antibody IOMA appeared to be a promising candidate for lineage-based vaccine design. In terms of epitope-based vaccine design, antibody VRC34.01 had few epitope segments, low epitope-glycan content, and high epitope-conformational variability, which may explain why VRC34.01-based design is yielding promising vaccine results.

bioinformatics

Colistin resistance prevalence in Escherichia coli from domestic animals in intensive breeding farms of Jiangsu Province, China

The global dissemination of colistin resistance has received a great deal of attention. Recently, the plasmid-mediated colistin resistance encoded by mcr-1 and mcr-2 genes in Escherichia coli (E.coli) strains from animals, food, and patients in China have been reported continuously. To make clear the colisin resistance and mcr gene spread in domestic animals in Jiangsu Province, we collected fecael swabs from pigs, chicken and cattle at different age distributed in intensive feeding farms. The selected chromogenic agar and mcr-PCR were used to screen the colisin resistance and mcr gene carriage. Colistin resistant E.coli colonies were identified from 54.25 % (440/811) pig faecal swabs, from 35.96 % (443/1232) chicken faecal swabs, and 26.92 % (42/156) from cattle faecal swabs. Of all the colisin resistant E.coli colonies, the positive amplifications of mcr-1 were significantly higher than mcr-2. The mcr-1 prevalence was 68.86 % (303/440) in pigs, 87.58 % (388/443) in chicken, and 71.43 % (30/42), compared with 46.82 % (206/440) in pigs, 14.90 % (66/443) in chicken, and 19.05 % (8/42) in cattle of prevalence of mcr-2. Co-occurrence of mcr-1 and mcr-2 was identified in 20 % (88/440) in pigs, 7.22 % (32/443) in chickens, and in 9.52 % (4/42) cattle. These data indicate that mcr was the most important colistin resistance mechanism. Interventions and alternative options are necessary to minimise further dissemination of mcr between food-producing animals and human.\n\nIMPORTANCEColistin is recognized one of the last defence lines for the treatment of highly resistant bacteria, but the emergence of resistance that conferred by a transferable plasmid-mediated mcr genes to this vital antibiotic is extremely disturbing. Here, we used E. coli as an index to monitor drug resistance in domestic animals (pigs, chicken and cattle). It was found that the colistin resistance widely occurred at all ages of domestic animals and the mcr-dependent mechanism dominated in E.coli. We also found that the elder and adult animals were a reservoir of resistant strains, suggesting a potential food safety issue and greater public health problems.

epidemiology