Biology subjects

Xia, W.

Publications and source records attributed to Xia, W..

47 records · Page 3Linked to original sources

bioRxiv2020

Environmental conditions and diffusion-limited microbial transfer drive specific microbial communities detected at different sections in oil-production reservoir with water-flooding

This study investigated the distribution of microbial communities in the oilfield production facilities of a water-flooding petroleum reservoir and the roles of environmental variation, microorganisms in injected water, and diffusion-limited microbial transfer in structuring the microbial communities. Similar bacterial communities were observed in surface water-injection facilities dominated by aerobic or facultative anaerobic Betaproteobacteria, Alphaproteobacteria, and Flavobacteria. Distinct bacterial communities were observed in downhole of the water-injection wells dominated by Clostridia, Deltaproteobacteria, Anaerolineae, and Synergistia, and in the oil-production wells dominated by Gammaproteobacteria, Betaproteobacteria, and Epsilonproteobacteria. Methanosaeta, Methanobacterium, and Methanolinea were dominant archaeal taxa in the water-injection facilities, while the oil-production wells were predominated by Methanosaeta, Methanomethylovorans, and Methanocalculus. Energy, nucleotide, translation, and glycan biosynthesis metabolisms were more active in the downhole of the water-injection wells, while bacterial chemotaxis, biofilm formation, two-component system, and xenobiotic biodegradation was associated with the oil-production wells. The number of shared OTUs and its positive correlation with formation permeability revealed differential diffusion-limited microbial transfer in oil-production facilities. The overall results indicate that environmental variation and microorganisms in injected water are the determinants that structure microbial communities in water-injection facilities, and the determinants in oil-bearing strata are environmental variation and diffusion-limited microbial transfer. IMPORTANCEWater-flooding continually inoculates petroleum reservoirs with exogenous microorganisms, nutrients, and oxygen. However, how this process influences the subsurface microbial community of the whole production process remains unclear. In this study, we investigated the spatial distribution of microbial communities in the oilfield production facilities of a water-flooding petroleum reservoir, and comprehensively illustrate the roles of environmental variation, microorganisms in injected water, and diffusion-limited microbial transfer in structuring the microbial communities. The results advance fundamental understanding on petroleum reservoir ecosystems that subjected to anthropogenic perturbations during oil production processes.

microbiology↗

bioRxiv2020

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease. Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

immunology↗

bioRxiv2020

The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure

Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-{beta}2 (Kap{beta}2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kap{beta}2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminate structural understandings on the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kap{beta}2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.

biophysics↗

bioRxiv2020

The dominance hierarchy of the female Yunnan snub-nosed monkeys (Rhinopithecus bieti)

Dominance hierarchies are common in social mammals, especially primates. The formation of social hierarchies is conducive to solving the problem of the allocation of scarce resources among individuals. From August 2015 to July 2016, we observed a wild, provisioned Yunnan snub-nosed monkey (Rhinopithecus bieti) group at Xiangguqing in Baimaxueshan National Nature Reserve, Yunnan Province, China. Aggressive and submissive behaviors were used to investigate dominance hierarchies between female individuals in the same one-male unit (OMU), and the grooming reciprocity index was used to detect reciprocal relationships between these females within the OMU. The results showed that loose social hierarchies exist among the females in each OMU, and more dominant individuals have higher grooming incomes. These results are consistent with the aggressive-submissive hypothesis and the resource control hypothesis.

animal behavior and cognition↗

bioRxiv2019

Proteomic Profiling and Biological Characterization of Extracellular Vesicles Isolated from Human Alzheimer’s Disease Brain Tissues

IntroductionExtracellular vesicles (EVs) from human Alzheimers disease (AD) biospecimens contain amyloid-{beta} peptide (A{beta}) and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined.\n\nMethodsEVs were isolated from the cortical grey matter of 20 AD and 18 control brains. Tau and A{beta} levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning.\n\nResultsLevels of pS396 tau and A{beta} were significantly elevated in AD EVs. High levels of neuron- and glia- specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy.\n\nDiscussionIn addition to A{beta} and tau, ANXA5, VGF, GPM6A and ACTZ are new signature proteins in AD EVs.

biochemistry↗

bioRxiv2019

A Single-Cell Immune Atlas of Triple Negative Breast Cancer Reveals Novel Immune Cell Subsets

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, which recently attracts great interest for immune therapeutic development. In this context, in-depth understanding of TNBC immune landscape is highly demanded. Here we report single-cell RNA sequencing results of 9683 tumor-infiltrated immune cells isolated from 14 treatment naive TNBC tumors, where 22 immune cell subsets, including T cells, macrophages, B cells, and DCs have been characterized. We identify a new T cell subset, CD8+CXCL8+ naive T cell, which associates with poor survival. A novel immune cell subset comprised of TCR+ macrophages, is found to be widely distributed in TNBC tumors. Further analyses reveal an up-regulation of molecules associated with TCR signaling and cytotoxicity in these immune cells, indicating TCR signaling activation. Altogether, our study provides a valuable resource to understand the immune ecosystem of TNBC. The novel immune cell subsets reported herein might be functionally important in cancer immunity.\n\nSIGNIFICANCEThis work demonstrates a single-cell transcriptome atlas of immune cells in treatment naive TNBC tumors, revealing novel immune cell subsets. This study provides a valuable resource to understand the immune ecosystem of TNBC, which will be helpful for the immunotherapeutic strategy design of TNBC.

immunology↗

bioRxiv2019

Clinical Significance of C4d Deposition in Renal Tissues from Patients with Primary Sj&oumlgren's Syndrome--A Preliminary Study

ObjectivesTo evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sjogrens syndrome (pSS)-associated renal impairments. MethodsWe retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when >75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score [≥]2 was considered TI-C4d positive and included in the TI-C4d+ group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0[~]10%, minimal), 2 (10%[~]50%, focal), and 3 (>50%, diffuse). ResultsGlomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score [≥]2. Patients in the TI-C4d+ group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d+ 132.5 [89.7, 165.5] vs. TI-C4d- 83.0 [70.7, 102.0] mol/L, P=0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. ConclusionsThe MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.

pathology↗

bioRxiv2018

Polymerization Kinetics Stability, Volumetric Changes, Apatite Precipitation, Strontium Release and Fatigue of Novel Bone Composites for Vertebroplasty

PurposeThe aim was to determine effects of diluent monomer and monocalcium phosphate monohydrate (MCPM) on polymerization kinetics and volumetric stability, apatite precipitation, strontium release and fatigue of novel dual-paste composites for vertebroplasty.\n\nMaterials and methodsPolypropylene (PPGDMA) or triethylene (TEGDMA) glycol dimethacrylates (25 wt%) diluents were combined with urethane dimethacrylate (70 wt%) and hydroxyethyl methacrylate (5 wt%). 70 wt% filler containing glass particles, glass fibers (20 wt%) and polylysine (5 wt%) was added. Benzoyl peroxide and MCPM (10 or 20 wt%) or N-tolyglycine glycidyl methacrylate and tristrontium phosphate (15 wt%) were included to give initiator or activator pastes. Commercial PMMA (Simplex) and bone composite (Cortoss) were used for comparison.\n\nATR-FTIR was used to determine thermal activated polymerization kinetics of initiator pastes at 50-80 {degrees}C. Paste stability, following storage at 4-37 {degrees}C, was assessed visually or through mixed paste polymerization kinetics at 25 {degrees}C. Polymerization shrinkage and heat generation were calculated from final monomer conversions. Subsequent expansion and surface apatite precipitation in simulated body fluid (SBF) were assessed gravimetrically and via SEM. Strontium release into water was assessed using ICP-MS. Biaxial flexural strength (BFS) and fatigue properties were determined at 37 {degrees}C after 4 weeks in SBF.\n\nResultsPolymerization profiles all exhibited an inhibition time before polymerization as predicted by free radical polymerization mechanisms. Initiator paste inhibition times and maximum reaction rates were described well by Arrhenius plots. Plot extrapolation, however, underestimated lower temperature paste stability. Replacement of TEGDMA by PPGDMA, enhanced paste stability, final monomer conversion, water-sorption induced expansion and strontium release but reduced polymerisation shrinkage and heat generation. Increasing MCPM level enhanced volume expansion, surface apatite precipitation and strontium release. Although the experimental composite flexural strengths were lower compared to those of commercially available Simplex, the extrapolated low load fatigue lives of all materials were comparable.\n\nConclusionsIncreased inhibition times at high temperature give longer predicted shelf-life whilst stability of mixed paste inhibition times is important for consistent clinical application. Increased volumetric stability, strontium release and apatite formation should encourage bone integration. Replacing TEGDMA by PPGDMA and increasing MCPM could therefore increase suitability of the above novel bone composites for vertebroplasty. Long fatigue lives of the composites may also ensure long-term durability of the materials.

bioengineering↗

bioRxiv2018

Divergent neuronal DNA methylation patterns across human cortical development: Critical periods and a unique role of CpH methylation

We have characterized the landscape of DNA methylation (DNAm) across the first two decades of human neocortical development in NeuN+ neurons using whole-genome bisulfite sequencing and compared them to non-neurons (primarily glia) and prenatal homogenate cortex. We show that DNAm changes more dramatically during the first five years of postnatal life than during the entire remaining period. We further refined global patterns of increasingly divergent neuronal CpG and CpH methylation (mCpG and mCpH) into six developmental trajectories and found that in contrast to genome-wide patterns, neighboring mCpG and mCpH levels within these regions were highly correlated. We then integrated paired RNA-seq data and identified direct regulation of hundreds of transcripts and their splicing events exclusively by mCpH levels, independently from mCpG levels, across this period. We finally explored the relationship between DNAm patterns and development of brain-related phenotypes and found enriched heritability for many phenotypes within DNAm features we identify.

neuroscience↗

bioRxiv2018

Identification of genes affecting saturated fat acid content in Elaeis guineensis by genome-wide association analysis

Oil palm is the highest yielding oil crop per unit area worldwide. Unfortunately, palm oil is often considered unhealthy. In particular, palmic acid (C16:0) is a major component of palm oil. In this study a total of 1 261 501 SNP markers were produced in a diversity panel of 200 oil palm individuals. Oil content in this population varied from 29.8% to 70.3%, palmic acid varied from 31.3% to 48.8%, and oleic acid varied from 31.3% to 50.1%. We identified 274 SNP markers significantly associated with fatty acid compositions; 44 candidate genes in the flanking regions of these SNPs were involved in fatty acid biosynthesis and metabolism. Among them, two acyl-ACP thioesterase B genes had differential expression patterns between the mesocarp and kernel, tissues which show different oil profiles in oil palm (high palmic acid and high lauric acid respectively). Overexpression of both genes caused a significant increase in palmic acid content, while overexpression of the EgFatB2 gene also caused an accumulation of lauric acid and myristic acid. Our research provides genome-wide SNPs, a set of markers significantly associated with fatty acid content, and validated candidate genes for future targeted breeding of lower saturated fat content in palm oil.

plant biology↗

bioRxiv2018

Persistence of Resident and Transplanted Genotypes of the Undomesticated Yeast, Saccharomyces paradoxus in Forest Soil

One might expect yeasts in soil to be highly dispersed via water or insects, forming ephemeral, genetically heterogeneous populations subject to competition and environmental stochasticity. Here, we report years-long persistence of genotypes of the yeast Sacchaormyces paradoxus in space and time. Within 1 km2 in a mixed hardwood forest on scales from centimeters to tens of meters, we detect persistence over 3 years of native genotypes, identified by SNPs genome-wide, of the wild yeast, Saccharomyces paradoxus around Quercus rubra and Q. alba. Yeasts were recovered by enrichment in ethanol-containing medium, which measures only presence or absence, not abundance. Additional transplantation experiments employed strains marked with spontaneous defects in the URA3 gene, which also confer resistance to 5-Fluoroorotic acid (5FOA). Plating soil suspensions from transplant sites on 5FOA medium permitted one-step quantification of yeast colony-forming units, with no interference from other unmarked yeasts or microorganisms. After an initial steep decrease in abundance, the yeast densities fluctuated over time, increasing in association with rainfall and decreasing in association with drought. After 18 months, the transplanted yeasts remain in place on the nine sites. In vitro transplantation experiments into non-sterile soil in petri dishes showed similar patterns of persistence and response to moisture and drought. To determine whether S. cerevisiae, not previously recovered from soils regionally, can persist in our cold-climate sites, we transplanted marked S. cerevisiae alone and in mixture with S. paradoxus in fall, 2017. Five months on, S. cerevisiae persist to the same extent as S. paradoxus.

ecology↗