Biology subjects

Zhang, P.

Publications and source records attributed to Zhang, P..

At least 19 recordsLinked to original sources

bioRxiv2026

In-cell structural analysis reveals a distinctive chloroplast ribosome in Chlamydomonas reinhardtii

Chloroplast ribosomes synthesize plastid-encoded components of photosynthetic machinery, yet their structure and organization remain poorly understood. We combined cryo-focused ion beam milling, cryo-electron tomography and subtomogram averaging to determine native chloroplast ribosomes in Chlamydomonas reinhardtii. The 4.4-4.9 [A] structure revealed a large arch-like extension on the small subunit (SSU). Comparisons with bacterial and plant chloroplast ribosomes, supported by proteomics, AlphaFold3 predictions and a recent atomic model, indicate that the arch is formed by insertions and extensions in SSU proteins. Classification resolved active, thylakoid-associated ribosomes with density adjacent to the nascent peptide exit and an arch-moved state enriched among thylakoid-associated particles, with coordinated displacement of the arch and beak. Phylogenetic analysis revealed an evolutionary mosaic: the uS3c insertion is broadly distributed across Chlorophyceae, whereas the uS2c insertion, uS5c and PSRP7 are concentrated in Chlamydomonadales, with PSRP7 also in Sphaeropleales. Nuclear-encoded components were recruited stepwise onto a plastid-encoded scaffold, with all four under comparable purifying selection. These findings link a lineage-specific SSU extension to ribosome dynamics, thylakoid association and evolution, highlighting the value of in-cell structural analysis.

plant biology↗

bioRxiv2018

A genetically encoded fluorescent sensor for rapid and specific in vivo detection ofnorepinephrine

Norepinephrine (NE) and epinephrine (Epi), two key biogenic monoamine neurotransmitters, are involved in a wide range of physiological processes. However, their precise dynamics and regulation remain poorly characterized, in part due to limitations of available techniques for measuring these molecules in vivo. Here, we developed a family of GPCR Activation-Based NE/Epi (GRABNE) sensors with a 230% peak {Delta}F/F0 response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second rapid kinetics, high specificity to NE vs. dopamine. Viral- or transgenic- mediated expression of GRABNE sensors were able to detect electrical-stimulation evoked NE release in the locus coeruleus (LC) of mouse brain slices, looming-evoked NE release in the midbrain of live zebrafish, as well as optogenetically and behaviorally triggered NE release in the LC and hypothalamus of freely moving mice. Thus, GRABNE sensors are a robust tool for rapid and specific monitoring of in vivo NE/Epi transmission in both physiological and pathological processes.

neuroscience↗

bioRxiv2018

SeqTailor: a user-friendly webserver for the extraction of DNA or protein sequences from next-generation sequencing data

Human whole-genome sequencing generally reveals about 4,000,000 genetic variants, including 20,000 coding variants, in each individual studied. These data are mostly stored as VCF-format files. Although many variant analysis methods accept VCF files as input, many other tools require DNA or protein sequences, particularly for splicing prediction, sequence alignment, phylogenetic analysis, and structure prediction. However, there is currently no existing online tool for extracting DNA or protein sequences for genomic variants from VCF files with user-defined parameters in a user-friendly, efficient, and standardized manner. We developed the SeqTailor webserver to bridge this gap. It can be used for the rapid extraction of (1) DNA sequences around genetic variants, with customizable window sizes, from the hg19 or hg38 human reference genomes; and (2) protein sequences encoded by the DNA sequences around genetic variants, with built-in SnpEff annotation and customizable window sizes, from human canonical transcripts. The SeqTailor webserver streamlines the sequence extraction process, and accelerates the analysis of genetic variant data with software requiring DNA or protein sequences. SeqTailor will facilitate the study of human genomic variation, by increasing the feasibility of sequence-based analysis and prediction. The SeqTailor webserver is freely available from http://shiva.rockefeller.edu/SeqTailor/.

bioinformatics↗

bioRxiv2018

Aperture Phase Modulation with Adaptive Optics: A Novel Approach for Speckle Reduction and Structure Extraction in Optical Coherence Tomography

AbstractSpeckle is an inevitable consequence of the use of coherent light in optical coherence tomography (OCT), and often acts as noise that obscures micro-structures of biological tissue. We here present a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) in OCT system: by modulating the phase inside the imaging system pupil aperture with a segmented deformable mirror, thus producing minor perturbations in the point spread function (PSF) to create un-correlated speckle pattern between B-scans, and further averaging to wash out the speckle but maintain the structures. It is a well-controlled and universal method which can efficiently determine the optimal range of phase modulation that minimizing speckle noise while maximizing image resolution and signal strength for different systems and/or samples. As an active method, its effectiveness and efficiency were demonstrated by both ex-vivo non-biological and in-vivo biological applications.

bioengineering↗

bioRxiv2018

Yes-associated protein (YAP) is required in maintaining normal ovarian follicle development and function

Yes-associated protein (YAP) is one of the major components of the Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, increasing evidence supports a critical role of the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. The ovary is one of few adult tissues that exhibit cyclical changes. Ovarian follicles, the basic units of ovary, are composed of a single oocyte surrounded by expanding layers of granulosa and theca cells. Granulosa cells (GCs) produce sex steroids and growth factors, which facilitate the development of the follicle and maturation of the oocyte. It has been reported that YAP is highly expressed in human GC tumors, but the role of YAP in normal ovarian follicle development is largely unknown. In current study, we examined YAP expression in bovine ovaries. We demonstrate that downstream hippo signaling effector protein, YAP and transcription co-activator, TAZ, are present and localization of both YAP and TAZ are density-dependent. Likewise, YAP and TAZ are critically involved in granulosa cell proliferation. Furthermore, reducing YAP in granulosa cells inhibits FSH-induced aromatase expression and estradiol biosynthesis. The data suggest that YAP plays an important role in the development of ovarian follicles and estradiol synthesis, which are necessary for maintaining normal ovarian function.

cell biology↗

bioRxiv2018

Autoantibodies and anti-microbial antibodies: Homology of the protein sequences of human autoantigens and the microbes with implication of microbial etiology in autoimmune diseases

Autoimmune disease is a group of diverse clinical syndromes with defining autoantibodies within the circulation. The pathogenesis of autoantibodies in autoimmune disease is poorly understood. In this study, human autoantigens in all known autoimmune diseases were examined for the amino acid sequences in comparison to the microbial proteins including bacterial and fungal proteins by searching Genbank protein databases. Homologies between the human autoantigens and the microbial proteins were ranked high, medium, and low based on the default search parameters at the NCBI protein databases. Totally 64 human protein autoantigens important for a variety of autoimmune diseases were examined, and 26 autoantigens were ranked high, 19 ranked medium to bacterial proteins (69%) and 27 ranked high and 16 ranked medium to fungal proteins (66%) in their respective amino acid sequence homologies. There are specific autoantigens highly homologous to specific bacterial or fungal proteins, implying potential pathogenic roles of these microbes in specific autoimmune diseases. The computational examination of the primary amino acid sequences of human autoantigens in comparison to the microbial proteins suggests that the environmental exposure to the commensal or pathogenic microbes is potentially important in pathogenesis of a majority of autoimmune diseases, providing a new direction for further experimental investigation in searching for new diagnostic and therapeutic targets for autoimmune diseases.

immunology↗

bioRxiv2018

Fungal polysaccharopeptides reduce obesity by richness of specific microbiota and modulation of lipid metabolism

The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, we show that protein-bound {beta}-glucan (PBG), one representative of Coriolus versicolor polysaccharopeptides which are broadly used as immune boosters and clinically implicated in treatment of cancers and chronic hepatitis, could be a potent anti-obesity agent. PBG could reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis revealed that PBG markedly increased the abundance of Akkermansia muciniphila although it didnt rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appeared that PBG altered host physiology and created an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduced obesity in recipient HFD-fed mice. Further, PBG was shown to promote lipid metabolism in microbiota-depleted mice. Thus, our data highlights that PBG might exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of lipid metabolism) manner. The fact that Coriolus versicolor polysaccharopeptides are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate the development of PBG as a novel drug for obesity treatment.

microbiology↗

bioRxiv2018

Regulatory networks of gene expression in maize (Zea mays) under drought stress and re-watering

Drought can severely limit plant growth and production. However, few studies have investigated gene expression profiles in maize during drought/re-watering. We compared drought-treated and water-sufficient maize plants by measuring their leaf relative water content, superoxide dismutase and peroxidase activities, proline content, and leaf gas exchange parameters (photosynthetic rates, stomatal conductance, and transpiration rates). We conducted RNA sequencing analyses to elucidate gene expression profiles and identify miRNAs that might be related to drought resistance. A GO enrichment analysis showed that the common DEGs (differently expressed genes) between drought-treated and control plants were involved in response to stimulus, cellular process, metabolic process, cell part, and binding and catalytic activity. Analyses of gene expression profiles revealed that 26 of the DEGs under drought encoded 10 enzymes involved in proline synthesis, suggesting that increased proline synthesis was a key part of the drought response. We also investigated cell wall-related genes and transcription factors regulating abscisic acid-dependent and -independent pathways. The expression profiles of the miRNAs miR6214-3p, miR5072-3p, zma-miR529-5p, zma-miR167e-5p, zma-miR167f-5p, and zma-miR167j-5p and their relevant targets under drought conditions were analyzed. These results provide new insights into the molecular mechanisms of drought tolerance, and may identify new targets for breeding drought-tolerant maize lines.\n\nAbbreviationsleaf relative water content: RWC, superoxide dismutase activity: SOD, peroxidase activity: POD, proline content: Pro, photosynthetic rates: Pn, stomatal conductance: Cond, transpiration rates: Tr.; quantitative real-time polymerase chain reaction: qPCR; abscisic acid; ABA; polyethylene glycol :PEG; Principal component analysis :PCA; polyacrylamide gel electrophoresis :PAGE\n\nHighlightThe study of physiology and molecular mechanism of maize laid a theoretical foundation for drought resistance breeding under drought stress and re-watering.

genomics↗

bioRxiv2018

Thyroid hormone signaling specifies cone subtypes in human retinal organoids

The mechanisms underlying the specification of diverse neuronal subtypes within the human nervous system are largely unknown. The blue (shortwavelength/S), green (medium-wavelength/M) and red (long-wavelength/L) cone photoreceptors of the human retina enable high-acuity daytime vision and trichromatic color perception. Cone subtypes are specified in a poorly understood two-step process, with a first decision between S and L/M fates, followed by a decision between L and M fates. To determine the mechanism controlling S vs. L/M fates, we studied the differentiation of human retinal organoids. We found that human organoids and retinas have similar distributions, gene expression profiles, and morphologies of cone subtypes. We found that S cones are specified first, followed by L/M cones, and that thyroid hormone signaling is necessary and sufficient for this temporal switch. Temporally dynamic expression of thyroid hormone degrading and activating proteins supports a model in which the retina itself controls thyroid hormone levels, ensuring low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining the mechanisms of cell fate specification during human development.\n\nOne sentence summaryCone specification in human organoids

developmental biology↗

bioRxiv2018

OptoGranules reveal the evolution of stress granules to ALS-FTD pathology

Stress granules are non-membranous assemblies of mRNA and protein that form in response to a variety of stressors. Genetic, pathologic, biophysical and cell biological studies have implicated disturbances in the dynamics of membrane-less organelles, such as stress granules, as a pathobiological component of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)1-12. This confluence of evidence has inspired the hypothesis that these diseases reflect an underlying disturbance in the dynamics and material properties of stress granules; however, this concept has remained largely untestable in available models of stress granule assembly, which require the confounding variable of exogenous stressors. Here we demonstrate the development and use of a light-inducible stress granule system, termed OptoGranules, which permits discrete, experimental control of the dynamics and material properties of stress granules in living cells in the absence of exogenous stressors. The nucleator in this system is Opto-G3BP1, a light-sensitive chimeric protein assembled from the intrinsically disordered region (IDR) and RNA-binding domain of G3BP1 combined with the light-sensitive oligomerization domain of Arabidopsis thaliana cryptochrome 2 (CRY2) photolyase homology region (PHR). Upon stimulation with blue light, Opto-G3BP1 initiates the rapid assembly of dynamic, cytoplasmic, liquid granules that are composed of canonical stress granule components, including G3BP1, PABP, TIA1, TIAR, eIF4G, eIF3{eta}, ataxin 2, GLE1, TDP-43 and polyadenylated RNA. With this system, we demonstrate that persistent or repetitive assembly of stress granules is cytotoxic and is accompanied by the evolution of stress granules to neuronal cytoplasmic inclusions that recapitulate the pathology of ALS-FTD.

neuroscience↗

bioRxiv2018

A multilevel statistical toolkit to study animal social networks: Animal Network Toolkit (ANT) R package

How animals interact and develop social relationships regarding, individual attributes, sociodemographic and ecological pressures is of great interest. New methodologies, in particular Social Network Analysis, allow us to elucidate these types of questions. However, the different methodologies developed to that end and the speed at which they emerge make their use difficult. Moreover, the lack of communication between the different software developed to provide an answer to the same/different research questions is a source of confusion. The R package Animal Network Toolkit (ANT) was developed with the aim of implementing in one package the many different social network analysis techniques currently used in the study of animal social networks. Hence, ANT is a toolkit for animal research allowing among other things to: 1) measure global, dyadic and nodal networks metrics; 2) perform data randomization: pre-network and network (node and link) permutations; 3) perform statistical permutation tests. The package is partially coded in C++ for an optimal coding speed, and it gives researchers a workflow from raw data to the achievement of statistical analyses, allowing for a multilevel approach: from individual position and role within the network, to the identification of interaction patterns, and the analysis of the overall network properties.

bioinformatics↗

bioRxiv2018

UDP-glucose:anthocyanidin 3-O-glucoside-2”-O-glucosyltransferase catalyzes further glycosylation of anthocyanins in purple Ipomoea batatas

Glycosylation contributes to the diversity and stability of anthocyanins in plants. The process is catalyzed by various glucosyltransferases using different anthocyanidin aglycones and glycosyl donors. An anthocyanidin 3-O-glucoside-2\"-O-glucosyltransferase (3GGT) from purple sweetpotato (cv. Ayamurasaki) served for the catalytic conversion of anthocyanidin 3-O-glucoside into anthocyanidin 3-O-sophoroside, which is functionally different from the 3GGT ortholog of Arabidopsis. The phylogenetic analysis indicates regioselectivity of 3GGT using UDP-xylose or UDP-glucose as the glycosyl is divergent between Convolvulaceae and Arabidopsis. Homology-based protein modeling and site-directed mutagenesis of Ib3GGT and At3GGT suggested that the Thr-138 of Ib3GGT is a key amino acid residue for UDP-glucose recognition and plays a major role in sugar donor selectivity. The wild type and ugt79b1 mutants of Arabidopsis plants overexpressing Ib3GGT produced the new component cyanidin 3-O-sophoroside. Moreover, Ib3GGT expression was associated with anthocyanin accumulation in different tissues during Ayamurasaki plant development and was regulated by the transcription factor IbMYB1. The localization assay of Ib3GGT showed that further glycosylation occurs in the cytosol and not endoplasmic reticulum. The present study revealed the function of Ib3GGT in further glycosylation of anthocyanins and its Thr-138 is the key amino acid residue for UDP-glucose recognition.

plant 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

A genetically-encoded fluorescent acetylcholine indicator

Acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body, yet cholinergic transmission in the majority of tissues/organs remains poorly understood due primarily to the limitations of available ACh-monitoring techniques. We developed a family of G-protein-coupled receptor activation-based ACh sensors (GACh) with sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo. GACh sensors were validated with transfection, viral and/or transgenic expression in a dozen types of neuronal and non-neuronal cells prepared from several animal species. In all preparations, GACh sensors selectively responded to exogenous and/or endogenous ACh with robust fluorescence signals that were captured by epifluorescent, confocal and/or two-photon microscopy. Moreover, analysis of endogenous ACh release revealed firing pattern-dependent release and restricted volume transmission, resolving two long-standing questions about central cholinergic transmission. Thus, GACh sensors provide a user-friendly, broadly applicable toolbox for monitoring cholinergic transmission underlying diverse biological processes.

neuroscience↗

bioRxiv2018

BED-domain containing immune receptors confer diverse resistance spectra to yellow rust

Introductory paragraph Introductory paragraph Main Methods Author contributions Data availability Competing interests References Crop diseases reduce wheat yields by ~25% globally and thus pose a major threat to global food security1. Genetic resistance can reduce crop losses in the field and can be selected for through the use of molecular markers. However, genetic resistance often breaks down following changes in pathogen virulence, as experienced with the wheat yellow (stripe) rust fungus Puccinia striiformis f. sp. tritici (Pst)2. This highlights the need to (i) identify genes that alone or in combination provide broad-spectrum resistance and (ii) increase our understanding of the underlying molecular mod ...

plant biology↗

bioRxiv2018

CD56 expression of intravascular trophoblasts defines a class of vasculopathy in preeclampsia and other pregnancy complications

We have discovered the expression of CD56 on the intravascular trophoblasts in the maternal spiral artery at implantation sites, and we have also found the similar phenotypic switch of intravascular trophoblasts in the decidual vasculopathy in preeclampsia. Currently we have examined 124 placentas from the patients with preeclampsia and 84 placentas from patients with other pregnancy associated complications without preeclampsia. CD56 expression on the intravascular trophoblasts can be seen in classic decidual vasculopathy such as fibrinoid medial necrosis and acute atherosis. In addition, partial involvement of the decidual vessels with classic vasculopathy can also be identified by CD56 expression. The cellular components of the classic vasculopathy in preeclampsia showed immunoreactivity to cytokeratin and CD68, in addition to CD56 expression, indicating the fetal trophoblastic cell origin. The classic decidual vasculopathy including acute atherosis and fibrinoid medial necrosis can be unified and designated as CD56-related vasculopathy. The CD56 related vasculopathy is associated not only to preeclampsia but also to other pregnancy related complications, such as gestational diabetes, placental infarcts, intervillous thrombosis and other fetal distress syndromes. Our study defined a spectrum of decidual vasculopathy spanning from the classic preeclampsia to other complications important to pregnancy that can be highlighted by CD56 expression, pointing to different direction of pathogenesis of preeclampsia and other pregnancy associated complications.

pathology↗

bioRxiv2018

Insulin Signaling-independent Activation of DAF-16 Shapes the Transcriptome during Normal Aging

The roles and regulatory mechanisms of transriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the expression of hundreds of genes in response to age-associated cellular stress. Most of the age-dependent DAF-16 targets are different from the canonical DAF-16 targets downstream of insulin signaling, indicating that activation of DAF-16 during aging is not due to reduced insulin signaling from DAF-2. Further analysis showed that it is due to the loss of proteostasis during aging, at least in part. We also found that without daf-16, dramatic gene expression changes occur as early as on adult day 2, indicating that DAF-16 acts to stabilize the transcriptome during normal aging. Our results thus reveal that normal aging is not simply a process in which the gene expression program descends into chaos due to loss of regulatory activities; rather, there is active transcriptional regulation that fights aging.

systems biology↗

bioRxiv2018

A widespread decrease of chromatin accessibility in age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profiled chromatin accessibility in the retina and retinal pigmented epithelium (RPE) from AMD patients and controls. Global decreases in chromatin accessibility occurr in RPE in early AMD, and in the retina with advanced disease, suggesting that dysfunction in RPE cells drives disease progression. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates epigenomic changes seen in AMD, providing an epigenetic link between the known risk factors for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the reduction in chromatin accessibility, identifying potential new targets for treatment of AMD.

genomics↗