Biology subjects

Xiao, S.

Publications and source records attributed to Xiao, S..

At least 109 records · Page 6Linked to original sources

bioRxiv2021

Gene expression in African Americans and Latinos reveals ancestry-specific patterns of genetic architecture

We analyzed whole genome and RNA sequencing data from 2,733 African American and Hispanic/Latino children to explore ancestry- and heterozygosity-related differences in the genetic architecture of whole blood gene expression. We found that heritability of gene expression significantly increases with greater proportion of African genetic ancestry and decreases with higher levels of Indigenous American ancestry, consistent with a relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of statistically significant ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most of the anc-eQTLs (89%) were driven by population differences in allele frequency, demonstrating the importance of measuring gene expression across multiple populations. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene-trait pairs using models trained in our admixed population than models trained in GTEx. Our study highlights the importance of large and ancestrally diverse genomic studies for enabling new discoveries of complex trait architecture and reducing disparities.

genetics↗

bioRxiv2021

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities

Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-{kappa}B signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders. SignificanceAn atmospheric trigger, the respirable particulate matter boost microglia pathogenic activities in the context of CNS demyelination by activating TLR-4/NF-{kappa}B signaling axis in animal models of immune- and toxicity-induced demyelination, as well as myelinogenesis during postnatal development.

neuroscience↗

bioRxiv2021

Dynamic surveillance of mosquitoes and their viromes in Wuhan during 2020.

Mosquitoes are medically important arthropod vectors and harbor a great variety of viruses. The population density, species and virome of mosquitoes varies according to geography and climate. To investigate the dynamic changes in the species composition and diversity of mosquitoes and their viromes in Wuhan, China, a total of 2,345 adult mosquitoes collected from different habitats including an urban residential area, two hospitals, a scenic area, and a pig farm in a rural region from April to October 2020 were subjected to morphological identification, RT-qPCR and metagenomic sequencing. The results indicated that the dominant presence of Culex mosquitoes was observed in both urban regions (90.32%, 1538/1703) and the pig farm (54.98%, 353/642). Viromes of Culex showed dynamic changes during the collection time. Several viruses, such as Culex flavivirus, Alphamesonivirus 1, Hubei mosquito virus 2 and Hubei mosquito virus 4, had seasonal changes and unimodal increases or declines. Other viruses, such as Wuhan mosquito virus 6, Hubei virga-like virus 2 and Zhejiang mosquito virus 3, were stable in all collected Culex and should be potential members of "core viromes". This study improves the understanding of the dynamic composition of mosquitoes and the viromes they carry and provides useful information for informing mosquito control and mosquito-borne disease prevention strategies.

microbiology↗

bioRxiv2021

Ovarian cysts and granulosa cell tumors develop after sublethal total body irradiation in mice

BackgroundLocalized and total body irradiation are used to treat certain cancers and also used prior to transplantation of stem cells or organs. However, the use of radiation also induces collateral damage to the cells of healthy tissue. Although the acute damage of radiation to oocytes is well known, the long-term effects induced by radiation to stromal cells and their relationship with age are still unclear. MethodsA total of 206 two-month-old female mice were whole-body exposed to gamma rays at doses of 0, 0.5, 1, 2, or 4 Gy, respectively. The mice were sacrificed at 3.5, 9, 12, or 18 months of age and pathological changes including cysts and tumors were assessed in the ovary and other organs. ResultsThe overall incidence of visible pathological changes of mice receiving irradiation was 33.7% in the ovary, but much lower in the liver, spleen, lung, thymus, and skin. Among these, the ovarian cyst formation rate was 24.7%, and tumor lesions were 10.2%, respectively, compared to 5% cyst formation and no tumor lesions among control, unirradiated mice. Statistical analysis showed that cyst formation was age, but not dose-dependent, whereas the formation of tumor lesions was dependent on both age and radiation dose. Pathology analysis indicated that most ovarian cysts originated from follicles and both tumor lesions analyzed originated from granulosa cells. ConclusionOvaries are highly susceptible to the effects of radiation. Long-term damage is increased after total body irradiation in mice, manifested by higher incidences of cyst formation and tumor lesions. The ovarian stromal-derived granulosa cells might play an essential role in these changes.

cancer biology↗

bioRxiv2021

High-speed multifocus phase imaging in thick tissue

Phase microscopy is widely used to image unstained biological samples. However, most phase imaging techniques require transmission geometries, making them unsuited for thick sample applications. Moreover, when applied to volumetric imaging, phase imaging generally requires large numbers of measurements, often making it too slow to capture live biological processes with fast 3D index-of-refraction variations. By combining oblique back-illumination microscopy and a z-splitter prism, we perform phase imaging that is both epi-mode and multifocus, enabling high-speed 3D phase imaging in thick, scattering tissues with a single camera. We demonstrate here 3D qualitative phase imaging of blood flow in chick embryos over a field of view of 546 x 546 x 137 m3 at speeds up to 47 Hz.

bioengineering↗

bioRxiv2021

Protective mitochondrial fission induced by stress responsive protein GJA1-20k

The Connexin43 gap junction gene GJA1 has one coding exon, but its mRNA undergoes internal translation to generate N-terminal truncated isoforms of Connexin43 with the predominant isoform being only 20 kDa in size (GJA1-20k). Endogenous GJA1-20k protein is not membrane bound, and has been found to increase in response to ischemic stress, localize to mitochondria, and mimic ischemic preconditioning protection in the heart. However, it is not known how GJA1-20k benefits mitochondria to provide this protection. Here, we identify that GJA1-20k polymerizes actin around mitochondria which induces focal constriction sites. Mitochondrial fission events occur within about 45 seconds of GJA1-20k recruitment of actin. Interestingly, GJA1-20k mediated fission is independent of canonical Dynamin Related Protein 1 (DRP1). We find that GJA1-20k induced smaller mitochondria have decreased reactive oxygen species (ROS) generation and, in hearts, provide potent protection against ischemia-reperfusion injury. The results indicate that stress responsive internally translated GJA1-20k stabilizes polymerized actin filaments to stimulate non-canonical mitochondrial fission which limits ischemic-reperfusion induced myocardial infarction.

cell biology↗

bioRxiv2021

Large-scale voltage imaging in the brain using targeted illumination

Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold membrane voltage dynamics from single neurons in the mammalian brain. To perform high speed voltage imaging, widefield microscopy remains an essential tool for recording activity from many neurons simultaneously over a large anatomical area. However, the lack of optical sectioning makes widefield microscopy more prone to background signal contamination, and thus far voltage imaging using fully genetically encoded voltage indicators remains limited to simultaneous sampling of a few cells over a restricted field-of-view. We here demonstrate a strategy for large scale voltage imaging using the fully genetically encoded voltage indicator SomArchon and targeted illumination. We implemented a simple, low-cost digital micromirror device based targeted illumination strategy to restrict illumination to the cells of interest, and systematically quantified the improvement of this microscopy design theoretically and experimentally with SomArchon expressing neurons in single layer cell cultures and in the brains of awake mice. We found that targeted illumination, in comparison to widefield illumination, increased SomArchon signal contrast and reduced background cross-contamination in the brain. Such improvement permitted the reduction of illumination intensity, and thus reduced fluorescence photobleaching and prolonged imaging duration. When coupled with a high-speed, large area sCMOS camera, we routinely imaged tens of spiking neurons simultaneously over minutes in the brain. Thus, the widefield microscopy design with an integrated targeted illumination system described here offers a simple solution for voltage imaging analysis of large neuron populations in behaving animals.

neuroscience↗

bioRxiv2021

Comparative genomics reveals evolutionary drivers of sessile life and left-right shell asymmetry in bivalves

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems. Across these ancient lineages, colony-founding larvae anchor themselves either by byssus production or by cemented attachment. The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis. Here, we sequenced the genome of C. hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry. Importantly, loss of the homeobox gene antennapedia (Antp) and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves. Evidence from comparative transcriptomics shows that the left-right asymmetrical C. hongkongensis plausibly diverged from the symmetrical Pinctada fucata in expression profiles marked by elevated activities of orthologous transcription factors and lineage-specific shell-related gene families including tyrosinases, which may cooperatively govern asymmetrical shell formation in Ostreoida oysters.

genomics↗

bioRxiv2021

Novel epigenetic-metabolic inhibitor combination treatment blocks platinum-induced ovarian cancer stem cell enrichment

High grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer. Platinum resistance is a common occurrence in HGSOC and a main cause of tumor relapse resulting in high patient mortality rates. Recurrent OC is enriched in aldehyde dehydrogenase (ALDH)+ ovarian cancer stem cells (OCSCs), which are resistant to platinum agents. We demonstrated that acute platinum treatment induced a DNA damage-dependent decrease in BRCA1 levels. In a parallel response associated with G2/M arrest, platinum treatment also induced an increase in expression of NAMPT, the rate limiting regulator of NAD+ production from the salvage pathway, and levels of NAD+, the cofactor required for ALDH activity. Concurrent inhibition of DNA methyltransferases (DNMTs) and NAMPT synergistically abrogated the platinum-induced increase in OCSCs. Combining pharmacological inhibitors of DNMT and NAMPT with carboplatin reduced tumorigenesis and OCSC percentage in vivo. We conclude that both epigenetic and metabolic alterations lead to platinum induced OCSC enrichment, providing preclinical evidence that in the neoadjuvant setting, combining DNMT and NAMPT inhibitors with platinum has the potential to reduce OC recurrence and avert the development of platinum resistance.

cancer biology↗

bioRxiv2021

Soil causes gut microbiota to flourish and total serum IgE levels to decrease in mice

Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil, soil microbes (in lieu of environmental microbes), or non-sterilized soil. Metagenomic sequencing results showed the intake of sterile soil i.e. inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune globulin E (IgE) levels induced by 2-4-dinitrofluorobenzene(DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential "prebiotic" promoting the reproduction and growth of some intestinal microorganisms that harbor bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.

ecology↗

bioRxiv2021

Incidence and Characteristics of Co-infection and Secondary Infection in Patients with COVID-19

ObjectiveThe etiology and epidemiology of co-infection and secondary infection in COVID-19 patients remain unknown. The study aims to investigate the occurrence and characteristics of co-infection and secondary infection in COVID-19 patients, mainly focusing on Streptococcus pneumoniae co-infections. MethodsThis study was a prospective, observational cohort study of the inpatients diagnosed with COVID-19 in two designated hospitals in south China enrolled between Jan 11 and Feb 22, 2020. The urine specimen was collected on admission and applied for pneumococcal urinary antigen tests (PUATs). Demographic, clinical and microbiological data of patients were recorded simultaneously. ResultA total of 146 patients with a confirm diagnosis of COVID-19 at the median age of 50.0 years (IQR 36.0-61.0) were enrolled, in which, 16 (11.0%) were classified as severe cases and 130 (89.0%) as non-severe cases. Of the enrolled patients, only 3 (2.1%) were considered to present the co-infection, in which 1 was co-infected with S.pneumoniae, 1 with B. Ovatus infection and the other one with Influenza A virus infection. Secondary infection occurred in 16 patients, with S. maltophilia as the most commonly isolated pathogen (43.8%), followed by P. aeruginosa (25.0%), E. aerogenes (25.0%), C. parapsilosis (25.0%) and A. fumigates (18.8%). ConclusionPatients with confirmed COVID-19 were rarely co-infected with Streptococcus pneumoniae or other pathogens, indicating that the application of antibiotics against CAP on admission may not be necessary in the treatment of COVID-19 cases.

microbiology↗

bioRxiv2020

PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

HIV vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

cell biology↗

bioRxiv2020

Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperature

BackgroundElevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown. ResultsHere we report that multigenerational exposure of Arabidopsis to extreme heat and moderate warming resulted in significantly increased mutation rates in single-nucleotide variants (SNVs) and small indels. We observed distinctive mutational spectra under extreme and moderately elevated temperatures, with significant increases in transition (C:G[->]T:A) and transversion (A:T[->]T:A) frequencies. Mutation occurred more frequently in intergenic regions, coding regions (especially nonsynonymous mutations), and transposable elements (TEs). At elevated temperatures, more mutations accumulated in genes associated with defense responses, DNA repair, and signaling, including the transcriptional response-related genes HSP70 and HSFA1A. Methylation was observed more frequently at mutation sites, indicating that it contributed significantly to the mutation process at elevated temperatures. Moreover, the mutations in lines and populations grown under elevated temperatures were significantly biased toward low gene density regions, special trinucleotides (GC context), tandem repeats, and adjacent simple repeats. Additionally, 24% (n = 64) of SNVs and 43% (n = 40) of indels found in all mutation accumulation lines overlapped significantly with genetic variations reported in 1001 Genomes, suggesting a non-uniform distribution of de novo mutations through the genome. ConclusionCollectively, our results suggest that elevated temperatures can accelerate the accumulation, and alter the molecular profiles, of DNA mutations in plants, thus providing significant insight into how environmental temperatures fuel plant evolution.

genetics↗

bioRxiv2020

A triple functional sensing chip for rapid detection of pathogenic Listeria monocytogenes

Here a triple functional sensing chip was created for L. monocytogenes detection by integrating three biomarkers (Listeriolysin O (LLO) at protein level, hly gene at genetic level, and acetoin at metabolic level). Liposome encapsulated catechol was used for LLO detection via LLO pore-forming ability. hly gene was specifically captured by using a thiolated capture probe on nanoporous gold (NPG). As an electroactive label, methylene blue was embedded in double-stranded structures to generate an electrochemical signal for hly detection. Combined with the electrocatalysis of NADH by NPG, the acetoin detection was achieved by measuring the consumption of NADH as a cofactor under acetoin reductase catalysis. Importantly, the L. monocytogenes detection results obtained by detecting three biomarkers using the chip can be mutually verified, which reduces the probability of false positives based on a single marker. Moreover, the detection time was reduced to about 90 min, making it a rapid and reliable tool for L. monocytogenes detection.

microbiology↗

bioRxiv2020

Ethylenediaminetetraacetic acid promotes the accumulation of nitric oxide

Ethylenediaminetetraacetic acid (EDTA) is a well-established chelating agent used in industry, agriculture, food, and medicine. However, the analysis of an EDTA-sensitive Arabidopsis thaliana mutant revealed that EDTA can significantly promote nitric oxide (NO) accumulation, indicating that EDTA has unexpected biological functions beyond its chelating activity. This finding challenges our current understanding about the effects of EDTA on biological systems. One Sentence SummaryAn analysis of ethylenediaminetetraacetic acid (EDTA)-sensitive mutants suggests that EDTA can promote the accumulation of nitric oxide.

molecular biology↗

bioRxiv2020

TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD

TDP-43 nuclear depletion and concurrent cytoplasmic accumulation in vulnerable neurons is a hallmark feature of progressive neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cellular stress signalling and stress granule dynamics are now recognized to play a role in ALS/FTD pathogenesis. Defective stress granule assembly is associated with increased cellular vulnerability and death. G3BP1 (Ras-GAP SH3-domain-binding protein 1) is a critical stress granule assembly factor. Here, we define that TDP-43 stabilizes G3BP1 transcripts via direct binding of a highly conserved cis regulatory element within the 3UTR. Moreover, we show in vitro and in vivo that nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels. Finally, we establish that G3BP1 transcripts are reduced in ALS/FTD patient neurons bearing TDP-43 cytoplasmic inclusions/nuclear depletion. Thus, our data suggest that, in ALS/FTD, there is a compromised stress granule response in disease-affected neurons due to impaired G3BP1 mRNA stability caused by TDP-43 nuclear depletion. These data implicate TDP-43 and G3BP1 loss of function as contributors to disease.

neuroscience↗

bioRxiv2020

An early Cambrian ecdysozoan with a terminal mouth but no anus

The ecdysozoans are the most diverse animal group on Earth1, 2. Molecular clock studies indicate that the ecdysozoans may have diverged and diversified in the Ediacaran Period3, 4, but unambiguous ecdysozoan fossils first appear in the earliest Cambrian and are limited to cycloneuralians5-7. Here we report new material of the early Cambrian microscopic animal Saccorhytus coronarius, which was previously interpreted as a deuterostome8. Saccorhytus coronarius is reconstructed as a millimetric and ellipsoidal meiobenthic animal with a spinose armor and an anterior mouth but no anus. Purported pharyngeal gills in support of the deuterostome hypothesis8 are shown to be taphonomic artifacts. Phylogenetic analyses indicate that Saccorhytus coronarius belongs to the total-group Ecdysozoa, highlighting the morphological and ecological diversity of early Cambrian ecdysozoans.

paleontology↗

bioRxiv2020

Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.

microbiology↗