Biology subjects

Zhu, Z.

Publications and source records attributed to Zhu, Z..

At least 271 records · Page 15Linked to original sources

bioRxiv2020

Dexmedetomidine attenuates the injury of H9C2 cardiomyocytes under Hypoxia/reoxygenation condition partly through the inhibition of endoplasmic reticulum stress

Background Myocardial ischemia-reperfusion injury (MIRI) has been confirmed to induce endoplasmic reticulum stress(ERS) during downstream cascade reaction when myocardial cell function keep deteriorating to a certain degree. The fact of matter is the clinical inconsistence with experimental outcomes still exist due to the mechanism has not been entirely clarified. Dexmedetomidine (DEX), a new generation anti-inflammatory and organ protector, has been testified can attenuate the IRI of heart. This study aimed to find out if DEX had the capacity to protect the injured cardiomyocytes under in vitro hypoxia/reoxygenation circumstance and if the ERS was totally or partly intervened.Methods H9C2 cells were subjected to cytotoxicity detection for 24h with DEX normally cultivated in several different concentrations. The proper hypoxia/reoxygenation (H/R) model parameter were concluded by the cell viability and injuries by cell counting kit-8(CCK8) and lactate dehydrogenase (LDH) release, when undergoing hypoxic condition for 3 h and reoxygenated for 3h, 6h,12h, and 24h, respectively. Also, the above index was assessed for H/R cardiomyocytes cultivated by various concentrations of DEX. The apoptosis, expression of) Glucose-regulated protein 78(GRP78), C/EBP homologous protein (CHOP), and caspase-12 were also examined in all groups.Results 1, 5 and 10 μM DEX in normal culture could significantly promote the proliferation of H9C2 (> 80%); the activity of H9c2 cells decreased to 62.67% (P < 0.05) at 3h of reoxygenation and to 36% at 6h of reoxygenation followed by 3h anoxic treatment; The cell viability of H9c2 cells in H/R groups incubated with 1 μM DEX increased 61.3%, and the LDH concentration in the supernatant was effectively lowered (−13.7, P < 0.05); H/R dramatically decreased the proportion of flow cytometry apoptosis and increased the expression of GRP78, CHOP and caspase-12, while both DEX and 4-phenyl butyric acid (4-PBA) could significantly reverse those above indicators. Additionally, DEX could induce deeper alterations than 4-PBA on the basis of H/R.Conclusion 1 μM DEX can dramatically attended the cell injuries, apoptosis, the expression of GRP78, CHOP and caspase-12 of H9C2 induced by 3h’ hypoxia and 3h’s reoxygenation. moreover, the functions of DEX went beyond the inhibition of ERS under this situation.View Full Text

scientific communication and education↗

bioRxiv2020

Spectrin-based Membrane Mechanics Is Asymmetric and Remodels during Neural Development

Perturbation of spectrin-based membrane mechanics causes hereditary elliptocytosis and spinocerebellar ataxia, but the underlying cellular basis of pathogenesis remains unclear. Here, we introduced the conserved disease-associated spectrin mutations into the C. elegans genome and studied the contribution of spectrin to neuronal migration and dendrite formation in developing larvae. The loss of spectrin generates an ectopic actin polymerization outside of the existing front and secondary membrane protrusions, leading to defective neuronal positioning and dendrite morphology in adult animals. Spectrin accumulates in the lateral and the rear of migrating neuroblasts and redistributes from the soma into the newly formed dendrites, indicating that the spectrin-based membrane skeleton is asymmetric and remodels to regulate actin assembly and cell shape during development. We affinity-purified spectrin from C. elegans and showed that its binding partner ankyrin functions with spectrin. Asymmetry and remodeling of membrane skeleton may enable spatiotemporal modulation of membrane mechanics for distinct developmental events. Significance StatementThe biomechanical regulation of neural development is largely unknown. The spectrin-based membrane skeleton is essential for the structural integrity of the plasma membrane. This study addresses the function and behavior of spectrin in neuroblast migration and dendrite formation. The loss of spectrin generates an ectopic actin polymerization outside of the existing front, leading to defective neuronal positioning and dendrite morphology. Spectrin is absent from the leading edge but accumulates in the posterior of migrating neuroblasts and redistributes from the soma into the nascent dendrites, indicating that the membrane skeleton is asymmetric and remodels. Asymmetry and remodeling of the membrane skeleton may enable spatiotemporal modulation of membrane mechanics for distinct developmental events.

developmental biology↗

bioRxiv2020

A Substantia Innominata-midbrain Circuit Controls a General Aggressive State

While aggressive behaviors are universal and essential for survival, uncontrollable and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors but not mating. By encoding a general aggressive response, the pSI-PAG circuit universally drives multiple aggressive behaviors and may provide a potential target for alleviating human pathological aggression. In BriefZhu et al. find that the posterior substantia innominata neurons universally drive aggressive behaviors by representing aggressive state and topography of aggression in mice. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/047670v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@19d72org.highwire.dtl.DTLVardef@7cc4corg.highwire.dtl.DTLVardef@1f5c3dborg.highwire.dtl.DTLVardef@d9743_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIpSI neuronal dynamics reflect aggressive state and the topography of aggression C_LIO_LIThe pSI-PAG circuit promotes arousal and elicits thirteen aggressive behaviors C_LIO_LIThe pSI controls various aggressive behaviors in an activity level-dependent manner C_LIO_LIInactivation of the pSI circuit blocks diverse aggressive behaviors but not mating C_LI

neuroscience↗

bioRxiv2020

Comprehensive transcriptome data of normal and Ascosphaera apis-infected western honeybee larval guts

ABSTRAmTApis mellifera ligustica is a well-known subspecies of western honeybee, Apis mellifera. Ascosphaera apis is a common fungal pathogen of honeybee larvae, resulting in Chalkbrood disease. In this article, deep sequencing of un-treated 4-, 5-, and 6-day-old larval guts (AmCK1, AmCK2, AmCK3) and A. apis-treated 4-, 5- and 6-day-old larval guts (AmT1, AmT2, AmT3) of Apis mellifera ligustica were conducted using Illumina HiSeq 4000 platform. In total, 85811046, 81962296, 85636572, 79267686, 82889882, and 100211796 raw reads were respectively yielded from above-mentioned six groups. The result of sequencing satuation analysis suggested that the sequencing depth in this work was enough to detect nearly all expressed genes. After quality control, 85739414, 81896402, 85573798, 79202304, 82828926, and 100128692 clean reads were obtained. Additionally, the GC content of each group was above 45.26%. Furthermore, 47035852, 65612676, 71803878, 62560904, 65018360, and 56278272 clean reads were mapped to the Apis mellifera genome, including 41221479, 61172916, 66724233, 57531335, 60245732, and 52638986 unique mapped clean reads, and 2078427, 986825, 915375, 1082925, 1097130, and 716436 multiple mapped clean reads. In addition, exons were the most abundant regions mapped by clean reads, follow by intergenic regions and introns. The strand-specific cDNA library-based RNA sequencing data documented here will faciliate study on molecualr mechanisms underlying host immune response and host-pathogen interaction during chalkbrood disease, and benefit understanding of non-coding RNA-mediated cross-kingdom regulation between A. m. ligustica larvae and A. apis. Value of the DataO_LIThis data reported here could be used to explore circRNAs, lncRNAs, mRNAs and their competing endogenous RNA networks involved in response of western honeybee larvae to Ascosphaera apis infection. C_LIO_LIThe current data contributes to better understanding mechanisms regulating host-pathogen interaction during chalkbrood disease. C_LIO_LIOur data can provide novel insights into understanding non-coding RNA-mediated cross-kingdom regulation between Apis mellifera ligustica and A. apis. C_LI

molecular biology↗

bioRxiv2020

Strand-specific cDNA library-based RNA sequencing dataset of un-infected and Ascosphaera apis-infected larval guts of Apis cerana cerana

Apis cerana cerana is a subspecies of eastern honeybee, Apis cerana. Ascosphaera apis is a widespread fungal pathogen of honeybee, leading to chalkbrood, which results in heavy losses for beekeeping industry. In this article, 4-, 5-, and 6-day-old larval guts of un-infected (AcCK1, AcCK2, and AcCK3) and A. apis-infected A. c. cerana (AcT1, AcT2, and AcT3) were sequenced by next generation sequencing. Totally, 73830148, 96586212, 94552744, 76672564, 90954858, and 83418832 raw reads were respectively produced from AcCK1, AcCK2, AcCK3, AcT1, AcT2, and AcT3. The sequencing depth was enough to detect all expressed genes. After strict quality control, 73775592, 96513798, 94495000, 76593924, 90870608 and 83339288 clean reads were obtained, with a mean GC content of 48.54%. Additionally, average Q20 and Q30 for aforementioned six groups were 98.10% and 94.36%, respectively. Moreover, 45302685, 65872823, 52709987, 49947838, 56476339, and 42657156 clean reads from above-mentioned six groups were mapped to the reference genome of Apis cerana, respectively. In addition, exons were the most abundant regions in reference genome mapped by clean reads, followed by intergenic regions and introns. Our data presented here can be used to identify long non-coding RNAs (lncRNAs), circlular RNAs (circRNAs), mRNAs and their regulatory networks engaged in response of eastern honeybee larvae to A. apis infection, and decipher molecular mechanisms underlying host-pathogen interaction. Value of the DataO_LIThe current data can be used for exploration of mRNAs, lncRNAs, circRNAs and their competing endogenous RNA (ceRNA) networks engaged in response of A. c. cerana larvae to A. apis infection. C_LIO_LIThis data provides a valuable genetic resource for better understanding non-coding RNA-mediated cross-kingdom regulation of eastern honey larvae to A. apis. C_LIO_LIThe accessible data offers novel insights into understanding the molecular mechanism underlying interaction between eastern honeybee larvae and A. apis. C_LI

bioinformatics↗

bioRxiv2020

PremPRI: Predicting the Effects of Single Mutations on Protein-RNA Interactions

Protein-RNA interactions are crucial for many cellular processes, such as protein synthesis and regulation of gene expression. Missense mutations that alter protein-RNA interaction may contribute to the pathogenesis of many diseases. Here we introduce a new computational method PremPRI, which predicts the effects of single mutations occurring in RNA binding proteins on the protein-RNA interactions by calculating the binding affinity changes quantitatively. The multiple linear regression scoring function of PremPRI is composed of 11 sequence- and structure-based features, and is parameterized on 248 mutations from 50 protein-RNA complexes. Our model shows a good agreement between calculated and experimental values of binding affinity changes with Pearson correlation coefficient of 0.72 and the corresponding root-mean-square error of 0.76 kcal mol-1, outperforming three other available methods. PremPRI can be used for finding functionally important variants, understanding the molecular mechanisms, and designing new protein-RNA interaction inhibitors. PremPRI is freely available at http://lilab.jysw.suda.edu.cn/research/PremPRI/.

bioinformatics↗

bioRxiv2020

PremPS: Predicting the Effects of Single Mutations on Protein Stability

Protein stability is related to its functional activities, and effect on stability or misfolding could be one of the major disease-causing mechanisms of missense mutations. Here we developed a novel machine learning computational method PremPS, which predicts the effects of single mutations on protein stability by calculating the changes in unfolding Gibbs free energy. PremPS uses only ten evolutionary- and structure-based features and is parameterized on five thousand mutations. Our approach outperforms previous methods and shows a considerable improvement in estimating the effects of mutations increasing protein stability. In addition, PremPS presents an outstanding performance in predicting the pathogenicity of missense mutations using an experimental dataset composed of two thousand non-neutral and neutral mutations. PremPS can be applied to many tasks, including finding functionally important variants, revealing the molecular mechanisms of functional influences and protein design. It is freely available at https://lilab.jysw.suda.edu.cn/research/PremPS/. Key PointsO_LIConsiderable improvement in estimating the effects of mutations increasing protein stability; C_LIO_LIComprehensive comparison with other 25 computational methods on different test sets; C_LIO_LIAn outstanding performance in predicting the pathogenicity of missense mutations; C_LIO_LIPremPS employs only ten distinct features belonging to six categories, and the most important feature describes evolutionary conservation of the site; C_LIO_LIThe webserver allows to do large-scale mutational scanning and takes about ten minutes to perform calculations for one thousand mutations from a normal size protein. C_LI

bioinformatics↗

bioRxiv2020

Pacific Biosciences long reads-based genome sequencing data from a widespread bee fungal parasite, Nosema ceranae

Nosema ceranae is a widespread fungal parasite that infects both adult honeybee and honeybee larvae, leading to microsporidiosis, which seriously affects bee health and apicultural industry. In this article, genome sequencing of clean spores of N. ceranae was conducted using third-generation Pacific Biosciences (PacBio) single molecule real time (SMRT) sequencing technology. In total, 152671 subreads were obtained after quality control of raw reads from PacBio SMRT sequencing, with a N50 and average length of 14422 bp and 11310 bp, respectively. Additionally, the length distribution of subreads was from 10000 bp to more than 50000 bp. Nineteen scaffords with a total length of 7354221 bp were assembled, and the N50, N90 and maximum scafford length were 728543 bp, 198795 bp and 1917792 bp, respectively. The GC content was 25.97%. Furthermore, by integration of genes predicted from de novo and homology-based methods, 3112 N. ceranae genes were finally assembled, with a total length of 2730179 bp and mean length of 877.31 bp. In addition, the total length and mean length of exons were 2657637 bp and 854 bp, respectively; and the total length and mean length of introns were 72542 bp and 23.31 bp, respectively. The genome sequencing data documented here will give deep insights into the molecular biology of N. ceranae, facilitate exploration of genes and pathways associated with toxin factors and infection-related factors, and benefit research on comparative genomics and phylogenetic diversity of Nosema species.

bioinformatics↗

bioRxiv2020

Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis

The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-[Kcy]B repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.

microbiology↗

bioRxiv2020

Genome-wide bisulfite sequencing data of normal and Ascosphaera apis-infected larval guts of eastern honeybee

Apis cerana cerana, a subspecies of eastern honey, Apis cerana, plays a specific role in beekeeping industry and ecosystem in China and other Asian countries. Larvae of A. c. cerana can be infected by Ascosphaera apis, the fungal pathogen of chalkbrood. In this article, normal 4-, 5-, and 6-day-old larval guts (AcCK1, AcCK2, AcCK3) and A. apis-infected 4-, 5- and 6-day-old larval guts (AcT1, AcT2, AcT3) of A. c. cerana workers were respectively harvested followed by DNA isolation, bisulfite conversion, cDNA library construction and Illumina sequencing. Based on genome-wide bisulfite sequencing, 79167210, 82175052, 79331489, 81051009, 74742842 and 74849091 raw reads were generated from AcCK1, AcCK2, AcCK3, AcT1, AcT2 and AcT3, and after quality control, 73417030 (92.73%), 76660370 (93.27%), 71804727 (90.44%), 75046507 (92.82%), 67487782 (90.30%) and 67367023 (90.04%) clean reads were obtained, respectively. Additionally, 73333333, 76533333, 71466667, 75066667, 67590965 and 67200000 clean reads were mapped to the reference genome of A. cerana, including 54656767, 58583415, 54127407, 57943220, 52547867 and 51295824 unique mapped clean reads, and 8624392, 8789458, 7531333, 7747337, 6249679 and 5394174 multiple mapped clean reads. The genome-wide bisulfite sequencing data reported here can be used for genome-wide identification of 5mC methylation sites in eastern honeybee larval guts and systematic investigation of DNA methylation-mediated host response to A. apis infection. Value of the dataO_LIThe current dataset contributes to genome-wide identification of 5mC methylation sites in normal and A. apis-infected larval guts of eastern honeybee. C_LIO_LIThe reported data could be used for systematic investigation of DNA methylation-mediated response of eastern honeybee larvae to A. apis infection. C_LIO_LIOur data offers a valuable genetic resource for better understanding epigenetic regulation mechanism involved in eastern honeybee larvae-A. apis interaction. C_LI

molecular biology↗

bioRxiv2020

High-quality chromosome-level genomes of two tilapia species reveal their evolution of repeat sequences and sex chromosomes

BackgroundTilapias are one of the most farmed fishes that are coined as aquatic chicken by the food industry. Like many other teleosts, Nile tilapia and blue tilapia exhibit very recent transition of sex chromosome systems since their divergence about 5 million years ago, making them a great model for elucidating the molecular and evolutionary mechanisms of sex chromosome turnovers. Studies into their sex-determining pathways are also critical for developing genetic sex control in aquaculture. ResultsWe report here the newly produced genomes of Nile tilapia and blue tilapia that integrate long-read sequencing and chromatin conformation data. The two nearly complete genomes have anchored over 97% of the sequences into linkage groups (LGs), and assembled majorities of complex repetitive regions including telomeres, centromeres and rDNA clusters. In particular, we inferred two episodes of repeat expansion at LG3 respectively in the ancestor of cichlids and that of tilapias. The consequential large heterochromatic region concentrated at one end of LG3 comprises tandem arrays of mRNA and small RNA genes, among which we have identified a candidate female determining gene Paics in blue tilapia. Paics show female-specific patterns of single-nucleotide variants, copy numbers and expression patterns in gonads during early gonadogenesis. ConclusionsOur work provide a very important genomic resource for functional studies of cichlids, and suggested that unequal distribution of repeat content that impacts the local recombination rate might make some chromosomes more likely to become sex chromosomes.

genomics↗

bioRxiv2020

Efficient detection of pre-proinsulin by double antibody sandwich ELISA

Abstract ObjectiveTo generate monoclonal antibodies against pre-proinsulin (PPI), and establish sandwich ELISA method to provide a basis for PPI detection in recombinant human insulin production. MethodsThe Balb /c mice were immunized with PPI, and the hybridomas secreting anti-PPI monoclonal antibodies were obtained by conventional cell fusion technique and ELISA screening.The antibody was purified using a Protein G gel column and identified for purity by SDS-PAGE. Pairing effect was found by the sandwich ELISA, and the specificity of the paired antibody was determined. A paired antibody with better specificity was selected to establish sandwich ELISA, and construct a quantitative curve, the accuracy and sensitivity of the method were evaluated. ResultsSix anti-PPI monoclonal antibodies were obtained, named P1, P2, P3, P4, P5 and P6, of which P5 had the highest titer. The sandwich ELISA method was established with P5 for plating and P2 for detection antibodie. The linear range of the quantitative curve of PPI by sandwich ELISA was 0. 645-82.5 pg/mL, the recovery was 89%-95%, and the limit of detection was 3.06 pg/mL. ConclusionSix monoclonal antibodies against PPI were generated and the sandwich ELISA method was established to detect PPI in process control and product release control for recombinant human insulin production.

bioengineering↗

bioRxiv2020

PacBio SMRT-based full-length transcriptome data of Ascosphaera apis mycelium and spore

Ascosphaera apis is an entomopathogenic fungus that exclusively infects honeybee larvae, resulting in chalkbrood disease, a widespread fungal disease damaging the beekeeping industry all over the world. In this article, purified mycelia (Aam) and spores (Aas) of A. apis pure culture under lab condition were sequenced using PacBio Sequel platform. In total, 13,302,489 and 9,911,345 subreads were yielded from Aam and Aas, respectively; 394,142 and 274,928 circular consensus sequence (CCS) reads were identified as being full-length non-chimeric (FLNC) reads, with a mean length of 2820 bp and 2602 bp, respectively. Furthermore, 174,095 and 103,845 corrected isoforms were identified, with a N50 length of 3543 bp and 3262 bp, respectively. The reported full-length transcriptome data of A. apis mycelium and spore will provide a valuable resource for improvement of genome and transcriptome annotations as well as better understanding of transcript structure such as alternative splicing and polyadenylation. Value of the dataO_LICurrent dataset offers a set of high-quality full-length transcripts of A. apis. C_LIO_LIThe data can facilitate the improvement of A. apis genome and transcriptome annotations. C_LIO_LIThis dataset benefits further exploration of alternative splicing and polyadenylation of A. apis mRNAs. C_LI

evolutionary biology↗

bioRxiv2020

MeRIP-seq and RNA-seq data of mycelium and spore of Ascosphaera apis, a widespread bee fungal pathogen

Ascosphaera apis is widespread fungal pathogen of honeybee larvae, causing chalkbrood, a chronic disease that weakens bee health and colony productivity. In this article, mecylia and spores of A. apis were respectively purified followed by RNA isolation, cDNA library construction, MeRIP-seq and RNA-seq. A total of 62,551,172, 41,773,158, 49,535,092 and 61,569,610 raw reads were produced from Aam_IP, Aas_IP, Aam_input and Aas_input groups, respectively. After quality control, 58,484,368, 37,381,432, 44,655,434 and 58,739,742 clean reads were obtained. Furthermore, 47,706,205, 31,356,690, 35,259,810 and 44,319,061 clean reads were mapped to the reference genome of A. apis, including 39,337,036, 26,731,957, 31,987,396 and 40,017,855 unique mapped reads, and 8,369,169, 4,624,733, 3,272,414 and 4,301,206 multiple mapped reads. Among them, 96.31%, 96.51%, 96.82% and 97.11% of clean reads were mapped to exons; 2.09%, 2.31%,1.83% and 1.81% to introns; 1.60%, 1.18%, 1.35% and 1.08% to intergenic regions. Value of the dataO_LIThe data can be used to investigate the relationship between the m6A modification extent and the transcript level in the A. apis transcriptome. C_LIO_LIThis dataset contributes to transcriptome-wide characterization of the m6A distributing patterns in mRNAs and non-coding RNAs in A. apis mycelium and spore. C_LIO_LICurrent data benefits new functions of m6A modification in the transcripts extensively modified by m6A in A. apis mycelium and spore. C_LIO_LIOur data could be used to characterize differential patterns of the m6A methylation between mycelium and spore of A. apis. C_LI

molecular biology↗

bioRxiv2020

Rottlerin ameliorates DSS-induced colitis by improving intestinal barrier function via activation of the Epac-2/Rap-1 signaling pathway.

OBJECTIVESRottlerin, a pan PDE inhibitor, has a variety of pharmacological activities, including enhancing barrier function and mediating anti-inflammatory activity by changing the distribution of occludin and ZO-1. Nevertheless, the function of rottlerin on Crohn disease (CD) keep unknown. Our aim of the study is to investigate the role of rottlerin on CD-like colitis and its mechanism. METHODSWild-type mice which were 8-10 weeks old were randomly divided into three treatment groups: (i) the normal feeding, no administration (control) group, (ii) the group administered 3% dextran sodium sulfate (DSS) alone, and (iii) the group administered rottlerin (100 mg/kg) and 3% DSS. In this study, the effect of rottlerin on the function and structure of the intestinal barrier was investigated, and the possible mechanism was discussed. We performed signaling pathway analysis and flow cytometry to identify the detailed mechanisms by which rottlerin (10 g/mL) treatment inhibits cell growth arrest and the attenuation of TJ proteins in LPS-treated FHs 74 int cells. RESULTSRottlerin treatment significantly ameliorated colitis induced by DSS in WT mice, which was manifested by a decrease in inflammation score, the attenuation of inflammatory factors and the inhibition of destruction on intestinal barrier structure. Rottlerin enhanced the levels of occludin and ZO-1, and improved the function of intestinal barrier, which may have been why rottlerin ameliorated colitis in WT mice. The anti-inflammatory effect of rottlerin may be partly due to the activation of Epac-2/Rap-1 signaling. CONCLUSIONSRottlerin may treat CD in humans via enhancing TJ proteins expression and improving the function of intestinal barrier.

cell biology↗

bioRxiv2020

Nanopore long-read transcriptome data of fungal pathogen of chalkbrood disease, Ascosphaera apis

Ascosphaera apis is a fungal pathogen that exclusively infects honeybee larvae, leading to chalkbrood disease, which damages the number of adult honeybees and colony productivity. In this article, A. apis mecylia and spores were respectively purified followed by Oxford Nanopore sequencing via PromethION platform. In total, 6,321,704 and 6,259,727 raw reads were generated from Aam and Aas, with a length distribution among 1 kb~10 kb. The quality (Q) scores of majority of raw reads were Q9 (Aam) and Q11 (Aas). Additionally, 5,669,436 and 6,233,159 clean reads were gained, among them 79.32% and 79.62% were identified as being full-length. The lengths of redundant reads-removed full-length transcripts were among 1 kb~8 kb and 1 kb~9 kb, and most abundant length for both was 1 kb. Furthermore, the length of redundant transcripts-removed clean reads was ranged from 1 kb~7 kb, with the largest group of 1 kb. The data reported here provides a beneficial genetic resource for improving genome and transcriptome annotations of A. apis and for exploring alternative splicing and polyadenylation of A. apis mRNAs. Value of the resultO_LICurrent dataset enables better understanding of the complexity of A. apis transcriptome. C_LIO_LIThe long-read transcriptome data can be used to identify of genes and transcripts associated with A. apis infection mechanism. C_LIO_LIThe accessible data provides full-length transcripts for improving gene structure and functional annotation of A. apis transcriptome. C_LIO_LIThis dataset could be utilized for investigation of alternative splicing and polyadenylation of A. apis mRNAs. C_LI

molecular biology↗

bioRxiv2020

Analyzing matched sets of microbiome data using the LDM and PERMANOVA

BackgroundMatched-set data arise frequently in microbiome studies. For example, we may collect pre- and post-treatment samples from a set of individuals, or use important confounding variables to match data from case participants to one or more control participants. Thus, there is a need for statistical methods for data comprised of matched sets, to test hypotheses against traits of interest (e.g., clinical outcomes or environmental factors) at the community level and/or the OTU (operational taxonomic unit) level. Optimally, these methods should accommodate complex data such as those with unequal sample sizes cross sets, confounders varying within sets, as well as continuous traits of interest. MethodsPERMANOVA is a commonly used distance-based method for testing hypotheses at the community level. We have also developed the linear decomposition model (LDM) that unifies the community-level and OTU-level tests into one framework. Here we present a strategy that can be used with both PERMANOVA and the LDM for analyzing matched-set data. We propose to include an indicator variable for each set as covariates, so as to constrain comparisons between samples within a set, and also permute traits within each set, which can account for exchangeable sample correlations. The flexible nature of PERMANOVA and the LDM allows discrete or continuous traits or interactions to be tested, within-set confounders to be adjusted, and unbalanced data to be fully exploited. ResultsOur simulations indicate that our proposed strategy outperformed alternative strategies in a wide range of scenarios. Using simulation, we also explored optimal designs for matched-set studies. The flexibility of PERMANOVA and the LDM for a variety of matched-set microbiome data is illustrated by the analysis of data from two real studies. ConclusionsIncluding set indicator variables and permuting within sets when analyzing matched-set data with PERMANOVA or the LDM is a strategy that performs well and is capable of handling the complex data structures that frequently occur in microbiome studies.

bioinformatics↗

bioRxiv2020

Classification of multigene families of African swine fever viruses

African swine fever virus (ASFV) is a large and complex double-stranded DNA virus that poses serious threats to the pig industry. It is well-accepted that the multigene family (MGF) proteins are extensively distributed in ASFVs and are generally classified into five families, including MGF-100, MGF-110, MGF-300, MGF-360 and MGF-505. Most MGF proteins, however, have not been well characterized and classified within each family. To bridge this gap, this study first classified the MGF proteins into 35 groups based on protein sequence homology. A web server for classifying the MGF proteins was then established and available for free at http://www.computationalbiology.cn/MGF/home.html. Results showed that the genetic diversity of the MGF groups varied widely, mainly due to the occurrence of indels. In addition, the MGF proteins were predicted to have large structural and functional diversity, and the MGF proteins of the same MGF family tended to have similar structure, location and function. Evolutionary analysis revealed the dynamic changes of the MGF proteins in the ASFV genomes, and more than half of MGF groups were presented in all ASFV genomes, which indicated the important role of MGF proteins in ASFVs. Overall, it is expected that the work would not only provide a detailed classification for MGF proteins, but also facilitate further research on MGF proteins.

bioinformatics↗