Biology subjects

Wu, X.

Publications and source records attributed to Wu, X..

At least 19 recordsLinked to original sources

bioRxiv2018

Bacteroides fragilis defense against Cronobacter sakazakii -induced pathogenicity by regulating the intestinal epithelial barrier function and attenuating both apoptotic and pyroptotic cell death

Cronobacter sakazakii (CS), an important pathogen, is associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of CS infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was a cross-talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, which revealed that ZY-312 inhibited CS invasion, CS-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. ZY-312 also decreased the expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities, and decreased the relative abundances of Proteobacteria, Gamma proteobacteria, but increased the relative abundance of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic, B. fragilis ZY-312, suppresses CS-induced NEC by modulating the pro-inflammatory response and dual cell death (apoptosis and pyroptosis).\n\nAuthor summaryCronobacter sakazakii, a major necrotizing enterocolitis pathogen, is used as a model microorganism for the study of opportunistic bacteria in the pathogenesis of necrotizing enterocolitis. Here, we have now unequivocally demonstrated that both apoptotic and pyroptotic stimuli contribute to the pathogenesis of Cronobacter sakazakii -induced necrotizing enterocolitis. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. We found that the ZY-312 defense against Cronobacter sakazakii-induced necrotizing enterocolitis by inhibiting Cronobacter sakazakii invasion, epithelial barrier dysfunction, the expression of inflammatory cytokines and dual cell death (pyroptosis and apoptosis). This study demonstrates the utility of ZY-312 as a promising probiotic agent for the prevention and treatment of various intestinal diseases, including NEC.

microbiology↗

bioRxiv2018

An oxide transport chain essential for balanced insulin signaling

Patients with overnutrition, obesity, the atherometabolic syndrome, and type 2 diabetes mellitus exhibit imbalanced insulin action, also called pathway-selective insulin resistance. To control glycemia, they require hyperinsulinemia that then overdrives ERK and hepatic de-novo lipogenesis. We recently reported that NADPH oxidase-4 regulates balanced insulin action. Here, we show that NADPH oxidase-4 is part of a new limb of insulin signaling that we abbreviate \"NSAPP\" after its five major proteins. The NSAPP pathway is an oxide transport chain that begins when insulin stimulates NADPH oxidase-4 to generate [Formula]. NADPH oxidase-4 hands [Formula] to superoxide dismutase-3 for conversion into H2O2. The pathway ends when aquaporin-3 channels H2O2 across the membrane to inactivate PTEN. Disruption of any component of the NSAPP chain, from NADPH oxidase-4 up to PTEN, leaves PTEN persistently active, thereby producing the same deadly pattern of imbalanced insulin action seen clinically. Unraveling the molecular basis for NSAPP dysfunction in overnutrition has now become a top priority.

cell biology↗

bioRxiv2018

The bunyavirus nonstructural protein NSs suppresses plant immunity to facilitate its own transmission by improving vector insect performance

Pandemics of vector-borne human and plant pathogens often rely on the behaviors of their arthropod vectors. Arboviruses, including many bunyaviruses, manipulate vector behavior to accelerate their own transmission to vertebrates, birds, insects, and plants. However, the molecular mechanism underlying this manipulation remains elusive. Here, we report that the non-structural protein NSs of orthotospovirus (order Bunyavirales, family Tospoviridae), is a key viral factor that indirectly modifies vector preference and increases vector performance. NSs suppresses the biosynthesis of volatile monoterpenes, which serve as repellents of the vector Western flower thrips (WFT, Frankliniella occidentalis) instead of using its known silencing suppressor activity. NSs directly interacts with and relocalizes the jasmonate (JA) signaling master regulator MYC2 and its two close homologs, MYC3 and MYC4, to disable JA-mediated activation of terpene synthase genes. The dysfunction of the MYCs subsequently attenuates host defenses, increases the attraction of thrips, and improves thrips fitness. These findings elucidate the molecular mechanism through which a bunyavirus manipulates vector behaviors and therefore facilitate disease transmission. Our results provide important insights into the molecular mechanisms by which tospoviruses NSs counteracts host immunity for pathogen transmission.\n\nAuthor summaryMost bunyaviruses are transmitted by insect vectors, and some of them can modify the behaviors of their arthropod vectors to increase transmission to mammals, birds, and plants. NSs is a non-structural bunyavirus protein with multiple functions that acts as an avirulence determinant and silencing suppressor. In this study, we identified a new function of NSs as a manipulator of vector behavior, independent of its silencing suppressor activity. NSs manipulates jasmonate-mediated immunity against thrips by directly interacting with several homologs of MYC transcription factors, the core regulators of the jasmonate-signaling pathway. This hijacking by NSs enhances thrips preference and performance. Many human- and animal-infecting members of the Bunyaviridales also encode NSs and could manipulate vector behavior to accelerate their own transmission. Therefore, our data support the hypothesis that the NSs protein may play conserved roles among various members of the Bunyaviridales in the modification of vector feeding behavior that evolved as a mechanism to enhance virus transmission.

microbiology↗

bioRxiv2018

Cross-cancer pleiotropic associations with lung cancer risk in African Americans

BackgroundIdentifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European descent individuals. Yet population-specific genetic variation can occur and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans.\n\nMethodsWe conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status.\n\nResultsWe identified three novel genomic regions significantly associated (FDR-corrected p-value < 0.10) with lung cancer risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and rs11658063 on 17q12). On chromosome16q22.2, rs7186207 was significantly associated with increased risk (OR=1.24, 95% CI: 1.12-1.38) and functional annotation using GTEx showed rs7186207 modifies DHODH gene expression. The risk allele at rs336958 on 5q14.3 was associated with reduced lung cancer risk (OR=0.68, 95% CI: 0.56-0.82), while the risk allele at rs11658063 on 17q12 was associated with increased risk (OR=1.24, 95% CI: 1.11-1.39).\n\nConclusionWe identified novel associations on chromosomes 5q14.3, 16q22.2, and 17q12, which contain HNF1B, DHODH, and HAPLN1 genes, respectively. SNPs within these regions have been previously associated with multiple cancers. This is the first study to examine cross-cancer pleiotropic associations for lung cancer in African Americans.\n\nImpactOur findings demonstrate novel cross-cancer pleiotropic associations with lung cancer risk in African Americans.

genetics↗

bioRxiv2018

Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the real or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQ1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 x 10-36, OR=2.29). Further stepwise conditional analysis revealed that DR{beta}1:37N has an independent protective effect on ACPA-positive RA (P = 5.81 x 10-16, OR=0.49). The DQ1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 x 10-5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQ1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DR{beta}1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.\n\nIn this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.

genetics↗

bioRxiv2018

Modified TCA/acetone precipitation of proteins for proteomic analysis

Protein extracts obtained from cells or tissues often require removal of interfering substances for the preparation of high-quality protein samples in proteomic analysis. A number of protein extraction methods have been applied to various biological samples. TCA/acetone precipitation and phenol extraction, a common method of protein extraction, is thought to minimize protein degradation and activity of proteases as well as reduce contaminants like salts and polyphenols. However, the TCA/acetone precipitation method relies on the complete pulverization and repeated rinsing of tissue powder to remove the interfering substances, which is laborious and time-consuming. In addition, by prolonged incubation in TCA/acetone, the precipitated proteins are more difficult to re-dissolve. We have described a modified method of TCA/acetone precipitation of plant proteins for proteomic analysis. Proteins of cells or tissues were extracted using SDS-containing buffer, precipitated with equal volume of 20% TCA/acetone, and washed with acetone. Compared to classical TCA/acetone precipitation and simple acetone precipitation, this protocol generates comparable yields, spot numbers, and proteome profiling, but takes less time (ca. 45 min), thus avoiding excess protein modification and degradation after extended-period incubation in TCA/acetone or acetone. The modified TCA/acetone precipitation method is simple, fast, and suitable for proteomic analysis of various plant tissues in proteomic analysis.

biochemistry↗

bioRxiv2018

A computational strategy for finding novel targets and therapeutic compounds for opioid dependence

Opioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database (http://daportals.org) for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators.

systems biology↗

bioRxiv2018

Childhood cerebellar tumors mirror conserved fetal transcriptional programs

The study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. Sonic Hedgehog medulloblastoma transcriptionally mirrors the granule cell hierarchy as expected, whereas Group 3 medulloblastoma resemble Nestin+ve stem cells, Group 4 medulloblastomas resemble unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumors demonstrates that many bulk tumors contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumors as a disorder of early brain development, and provide a proximate explanation for the peak incidence of cerebellar tumors in early childhood.

cancer biology↗

bioRxiv2018

Overexpressed microRNA-141-3p enhance proliferation via targeting PLAG1 in non-diabetic macrosomia

Several studies have shown microRNAs (miRNAs) could regulate the placental development, yet the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear. The key miRNA that abnormal expressed in NDFMS placentas was screened out by miRNA microarray and verified using qRT-PCR in 91 subjects. The effects of the key miRNA were verified by proliferation assay and invasion assay in HTR-8/SVneo cell, and also in pregnant C57BL/6J mice. miR-141-3p was determined as the key miRNA with the most significant difference, which could promote the proliferation and invasion by regulating the expression of target gene PLAG1. Overexpression of PLAG1 could reverse the effect of cell proliferation and invasion ability caused by miR-141-3p overexpression. Significant difference in fetal birth weight was observed between the control group and treated group with miR-141-3p agomir in late pregnancy, but not in early pregnancy. This study revealed miR-141-3p could increase the proliferation of placenta to participate in the occurrence and development of NDFMS through regulating PLAG1 expression.

developmental biology↗

bioRxiv2018

Condensin-dependent chromatin condensation represses transcription globally during quiescence

Quiescence is a stress-resistant state in which cells reversibly exit the mitotic cell cycle and suspend most cellular processes. Quiescence is essential for stem cell maintenance and its misregulation is implicated in tumor formation. One of the conserved hallmarks of quiescent cells, from Saccharomyces cerevisiae to humans, is highly condensed chromatin. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide to elucidate mechanisms and functions of condensed chromatin in quiescent S. cerevisiae cells. We describe previously uncharacterized chromatin domains on the order of 10-60 kilobases that in quiescent cells are formed by condensin-mediated chromatin loops. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. We further demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. We propose that condensin-dependent condensation of chromatin represses transcription throughout the quiescent cell genome.

molecular biology↗

bioRxiv2018

The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. In IgAN, immune complex deposite in glomerular mesangium, which induce inflammation and affect the kidneys normal functions. However, the exact pathogenesis of IgAN is still incompletely understood. Further, in current practice the clinical diagnosis relies on needle biopsy on renal tissue. Therefore, a non-invasive method for clinical diagnosis and prognosis surveillance of the disease is in high demand. In this paper, we investigated both the T cell receptor bata chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire of kidney infiltrating and circulating lymphocytes of IgAN patients by immune repertoire high throughput sequencing. We found that the features of TCRB and IGH in the renal tissues were remarkably different from that in blood, including a decreased repertoire diversity and increased IgA and IgG frequency, and more activated B cells. The CDR3 length of PBMC TCRB and IGH in patients is significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clone selection. We also found that the IgA1 frequency in the PBMC of IgAN is significant higher than that in other Nephropathy (NIgAN) and healthy control, which is consistent with the previous reports on the level of IgA1 producing B cells and serum IgA1. Significantly, we identified a set of IgAN disease related TCRB and IGH CDR3s, which can be used to distinguish IgAN from NIgAN and healthy controls from the blood with high accuracy. These results indicated that TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for IgAN diagnosis. The characteristics of kidney infiltrating and circulating lymphocytes repertoire shed light on IgAN detection, treatment and surveillance.

immunology↗

bioRxiv2018

Quantification of Enterohemorrhagic Escherichia coli O157:H7 proteome using TMT-Based Analysis

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen responsible for diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). EHEC infection is distributed worldwide and numerous outbreaks of diseases caused by enterohemorrhagic have been reported. To promote a comprehensive insight into the molecular basis of EHEC O157:H7 physiology and pathogenesis, the combined proteome of EHEC O157:H7 strains, Clade 8 and Clade 6 isolated from cattle in Argentina, and the standard EDL933 (clade 3) strain has been analyzed. TMT (Tandem Mass Tags)-based quantitative proteomic and emPAI analyses were performed to estimate the protein abundance in EHEC proteome. 2,234 non-redundant proteins of EHEC O157:H7 were identified. A comparison of this result with in silico data of EHEC O157:H7 genome showed that approximately 40% of the predicted proteome of this pathogen were covered. According to the emPAI analysis, 85 proteins were among the most abundant (e.g. GAPDH, FliC H-antigen, Enolase, and GroEL). Tellurite resistance proteins were also highly abundant. COG analysis showed that although most of the identified proteins are related to cellular metabolism, the majority of the most abundant proteins are associated with translation processes. A KEGG enrichment analysis revealed that Glycolysis / Gluconeogenesis was the most significant pathway. On the other hand, the less abundant detected proteins are those related to DNA processes, cell respiration and prophage. Among the proteins that composed the Type III Secretion System, the most abundant protein was EspA. Altogether, the results show a subset of important proteins that contribute to physiology and pathogenicity of EHEC O157:H7.\n\nIMPORTANCEThe study of the abundance of proteins present within a complex mixture of proteins in a cell, under different conditions, can provide important information about the activities of individual protein components and protein networks that are cornerstones for the comprehension of physiological adaptations in response to biological demands promoted by environmental changes. We generated a comprehensive and accurate quantitative list of EHEC O157:H7 proteome, which provides a description of the most abundant proteins produced by this pathogen that were related to physiology and pathogenesis of EHEC. This study provides information and extends the understanding on functional genomics and the biology of this pathogen.

microbiology↗

bioRxiv2018

B7-H1(PD-L1) confers chemoresistance through ERK and p38 MAPK pathway in tumor cells

Development of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of patients with cancer. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance remains underestimated. It has been recently observed that overexpression of B7-H1(PD-L1) confers chemoresistance in human cancers, however the underlying mechanisms are unclear. Here we show that the development of chemoresistance depends on the increased activation of ERK pathway in tumor cells overexpressing B7-H1. Conversely, B7-H1 deficiency renders tumor cells susceptible to chemotherapy in a cell-context dependent manner through activation of the p38 MAPK pathway. B7-H1 in tumor cells associates with the catalytic subunit of a DNA-dependent serine / threonine protein kinase (DNA-PKcs). DNA-PKcs is required for the activation of ERK or p38 MAPK in tumors expressing B7-H1, but not in B7-H1 negative or B7-H1 deficient tumors. Ligation of B7-H1 by anti-B7-H1 monoclonal antibody (H1A) increased the sensitivity of human triple negative breast tumor cells to cisplatin therapy in vivo. Our results suggest that B7-H1(PD-L1) expression in cancer cells modifies their chemosensitivity towards certain drugs and targeting B7-H1 intracellular signaling pathway is a new way to overcome cancer chemoresistance.

cancer biology↗

bioRxiv2018

Identification of a Novel Neutralizing and Two Non-Neutralizing Epitopes on Epstein-Barr Virus gp350 Protein

Prevention of Epstein-Barr virus (EBV) primary infection has focused on generating neutralizing antibodies (nAbs) targeting the major envelope glycoprotein gp350/220 (gp350). To date, eight gp350 epitopes have been identified, but only one has elicited nAbs. In this study, we generated 23 hybridomas that produced anti-gp350 antibodies. We compared the candidate anti-gp350 antibodies to nAb-72A1 by: (1) testing their ability to detect gp350 using ELISA, flow cytometry, and immunoblot; (2) sequencing their heavy and light chain complementarity-determining regions (CDRs); (3) measuring the ability of each monoclonal antibody (mAb) to neutralize EBV infection in vitro; and (4) mapping the gp350 amino acids bound by the mAbs using RepliTope peptide microarrays. Eight antibodies recognized both denatured and non-denatured gp350, whereas five failed to react with denatured gp350 but recognized native gp350, suggesting they recognized conformational epitope(s). Sequence analysis of the heavy and light chain variable regions of the hybridomas identified 15 as mAbs with novel CDR regions unique from those of nAb-72A1. Seven of the new mAbs neutralized EBV in vitro, with HB20 and HB17 reducing EBV infection by 40% and >60%, and >30% and 80%, at 10 g/ml and 50 g/ml, respectively. Epitope mapping identified nine epitopes and defined their core residues, including two unique immunodominant epitopes, 253TPIPGTGYAYSLRLTPRPVSRFL253 and 875LLLLVMADCAFRRNLSTSHTYTTPPY899, and a novel nAb epitope 381GAFASNRTFDIT392. This study provides comprehensive in vitro mapping of the exact residues defining nine epitopes of EBV gp350. Our findings will inform novel strategies to design optimal EBV vaccines capable of conferring broader protection against the virus.\n\nImportanceNeutralizing antibodies (nAbs) directed against Epstein-Barr virus envelope glycoprotein gp350/220 (gp350) are generated in humans upon infection or immunization, and are thought to prevent neonatal infection. However, clinical use of exogenous nAbs (passive immunization) is limited to a single study using the only well-characterized nAb, 72A1. The gp350 ectodomain contains at least eight unique B-cell binding epitopes; two of these epitopes are recognized by nAb-72A1. The exact amino acid residues of the other six epitopes and their role in generating nAbs has not been elucidated. We used our 15 newly generated and fully characterized monoclonal antibodies and a peptide-overlapping RepliTope array to provide a comprehensive map of the core amino acid residues that define epitopes of gp350 and to understand their role in generating nAbs. These results will inform design of better-targeted gp350 peptide vaccines that contain only protective epitopes, which will focus the B-cell response to produce predominantly nAbs.

immunology↗

bioRxiv2018

Exogenous putrescine alleviates photoinhibition caused by salt stress through increasing cyclic electron flow in cucumber

When plants suffer from abiotic stresses, cyclic electron flow (CEF) is induced for photoprotection. Putrescine (Put), a main polyamine in chloroplasts, plays a critical role in stress tolerance. To elucidate the mechanism of Put regulating CEF for salt-tolerance in cucumber leaves, we measured chlorophyll fluorescence, P700 redox state, ATP and NADPH accumulation and so on. The maximum photochemical efficiency of PSII (Fv/Fm) was not influenced by NaCl and/or Put, but the activity of PSI reaction center (P700) was seriously inhibited by NaCl. Salt stress induced high level of CEF, moreover, NaCl and Put treated plants exhibited much higher CEF activity and ATP accumulation than single salt-treated plants to provide adequate ATP/NADPH ratio for plants growth. Furthermore, Put decreased the trans-membrane proton gradient ({Delta}pH), accompanied by reducing the pH-dependent non-photochemical quenching (qE) and increasing efficient quantum yield of PSII (Y(II)). The ratio of NADP+/NADPH in salt stressed leaves was significantly increased by Put, indicating that Put relieved over-reduction pressure at PSI accepter side. Taken together, our results suggest that exogenous Put enhances CEF to supply extra ATP for PSI recovery and CO2 assimilation, decreases {Delta}pH for electron transport related proteins staying active, and enable the non-photochemical quenching transformed into photochemical quenching.

plant biology↗

bioRxiv2018

Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice

Amyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disease with fast progression. Mutations of the CREST gene (also known as SS18L1) are identified in sporadic ALS patients. Whether CREST mutations may lead to ALS remained largely unclear. In this study, we showed that the ALS-related CREST-Q388X mutation exhibited loss-of-function effects. Importantly, we found that microglial activation were prevalent in CREST haploinsufficieny mice and the Q394X mice mimicking the human CREST Q388X mutation. Furthermore, we showed that both CREST haploinsufficieny and the Q394X mice displayed deficits in motor coordination. Finally, we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons, via histone deacetylation, providing the molecular mechanisms underlying inflammatory responses lack of CREST. These findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors, suggesting potential therapeutic methods through inflammation pathways.\n\nIn BriefCheng et al. discovered that neuronal loss of CREST reduces the protein level of FUS, de-represses the transcriptional inhibition of chemokine genes which in turn causes microglial activation and proinflammation, and ultimately leads to axonal degeneration of motor neurons and impairment of locomotion.

neuroscience↗

bioRxiv2018

Genome-wide survey and expression analysis of the SLAC/SLAH gene family in pear (Pyrus bretschneideri) and other members of the Rosaceae

S-type anion channels (SLAC/SLAHs), which play important roles in plant anion (such as nitrate and chloride) transport, growth and development, abiotic stress responses and hormone signaling. However, there is far less information about this family in Rosaceae species. We performed a genome-wide analysis and identified SLAC/SLAH gene family members in pear (Pyrus bretschneideri) and four other species of Rosaceae (Malus domestica, Prunus persica, Fragaria vesca and Prunus mume). A total of 21 SLAC/SLAH genes were identified from the five Rosaceae species. Based on the structural characteristics and a phylogenetic analysis of these genes, the SLAC/SLAH gene family could be classified into three main groups (I, II and III). The evolutionary analysis showed that the SLAC/SLAH gene family was comparatively conserved during the evolution of Rosaceae species. Transcriptome data demonstrated that PbrSLAC/SLAH genes were detected in all parts of the pear. However, PbrSLAC1 showed a higher expression level in leaf, while PbrSLAH2/3 was mainly expressed in roots. In addition, PbrSLAC/SLAH genes were only located on the plasma membrane in transient expression experiments in Arabidopsis protoplasts cells. These results provide valuable information that increases our understanding of the evolution, expression and functions of the SLAC/SLAH gene family in higher plants.

bioinformatics↗

bioRxiv2018

A Genetic Program Mediates Cold-warming Response and Promotes Stress-induced Phenoptosis in C. elegans

How multicellular organisms respond to and are impacted by severe hypothermic stress is largely unknown. From C. elegans screens for mutants abnormally responding to cold-warming stimuli, we identify a molecular genetic pathway comprising ISY-1, a conserved uncharacterized protein, and ZIP-10, a bZIP-type transcription factor. ISY-1 gatekeeps the ZIP-10 transcriptional program by regulating the microRNA mir-60. Downstream of ISY-1 and mir-60, zip-10 levels rapidly and specifically increase upon transient cold-warming response. Prolonged zip-10 up-regulation induces several protease-encoding genes and promotes stress-induced organismic death, or phenoptosis, of C. elegans. zip-10 deficiency confers enhanced resistance to prolonged cold-warming stress, more prominently in adults than larvae. We conclude that the ZIP-10 genetic program mediates cold-warming response and may have evolved to promote wild population kin selection under resource-limiting and thermal stress conditions.

genetics↗