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Zhang, A.

Publications and source records attributed to Zhang, A..

At least 181 records · Page 10Linked to original sources
bioRxiv2022

Visual Perception of 3D Space and Shape In Time - Part IV: 3D Shape Recognition by 3D Rotation

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear at any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size upfront at the object center, the direct comparison between the one-sized memory and an incoming new image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly as we experience it in our daily lives? This paper specifically addresses the recognition of human faces with arbitrary 3D orientation in the [Roll, Yaw, Pitch] axes. According to our new model of NHT (Neural Holography Tomography), space is represented by time utilizing the phase of the alpha brainwave. This principle should be applicable to any mental rotation in 3D; thus, it predicts that extra time is required to perceive a rotated face to revolve it back to upright by the constant-speed alpha wave. To assess this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of upright unfamiliar faces. Following the memorization phase, similar stimuli with a wide range of rotating faces in 3D were presented, and RTs were recorded. As expected, the memorized upfront face was the fastest RT. The excess of the RT was observed proportional to the rotating angle in all [Roll, Yaw, Pitch] axes. Roll had the flattest slope, whereas upper Pitch was the steepest. We suspect that Roll is the swiftest mental operation because it can be conducted by the linear frame translation on the log-polar retinotopy of the visual cortex.

neuroscience↗
bioRxiv2021

Adolescent rats extend help to outgroup members, highlighting a neural network for group identity categorization.

Prosocial behavior, in particular helping others in need, occurs preferentially in response to the perceived distress of ones own group members, or ingroup. The development of neural mechanisms underlying social selectivity towards ingroup members are not well established. Here, we used a rat helping behavior test to explore the development and neural basis of ingroup bias for prosocial behavior in adolescent rats. We previously found that adult rats selectively help others from their own social group, and that this selectivity is associated with activation in reward and motivation circuits. Surprisingly, we found that adolescent rats helped both ingroup and outgroup members, evidence suggesting that ingroup bias emerges in adulthood. Analysis of brain-wide neural activity, indexed by expression of the early-immediate gene c-Fos, revealed increased activity for ingroup members across a broad set of regions, which was congruent for adults and adolescents. However, adolescents showed reduced hippocampal and insular activity, and increased orbitofrontal cortex activity compared to adults. Adolescent rats who did not help trapped others also demonstrated increased amygdala connectivity. Together, these findings demonstrate that biases for group-dependent prosocial behavior develop with age in rats and suggest that specific brain regions contribute to this prosocial selectivity, overall pointing to possible targets for the functional modulation of ingroup bias. One Sentence SummaryProsocial selectivity increases with age in parallel with hippocampal and insular activation, providing insight into the neural classification of group membership.

neuroscience↗
bioRxiv2021

The regeneration factors ERF114 and ERF115 act as transducers of mechanical cues to developmental pathways

Plants show an unparalleled regenerative capacity, allowing them to survive severe stress conditions, such as injury, herbivory attack and harsh weather conditions. This potential not only replenishes tissues and restores damaged organs, but can also give rise to whole plant bodies, highlighting the intertwined nature of development and regeneration. It suggests that regeneration and developmental processes respond to the same upstream signals, but how a cell knows which of the two processes to engage is currently unknown. Here, we demonstrate that next to being regulators of regeneration, ETHYENE RESPONSE FACTOR 114 (ERF114) and ERF115 govern developmental growth in the absence of wounding or injury. Increased ERF114 and ERF115 activity is correlated with enhanced xylem maturation and lateral root formation, whereas their knockout results in a decrease in lateral roots and xylem connectivity following grafting. Moreover, we provide evidence that mechanical cues contribute to ERF114 and ERF115 expression in correlation with BZR1 mediated brassinosteroid signaling under both regenerative and developmental conditions. Antagonistically, negative regulation of cell wall extensibility via cell wall-associated mechanosensory FERONIA signaling suppresses their expression under both conditions. Our data suggest a molecular framework in which mechanical perturbations too great to be compensated by adaptive cell wall remodeling results in strong ERF114 and ERF115 expression, switching their role from developmental to regenerative regulators. One-Sentence SummaryMechanical cues drive ERF114/ERF115 expression during lateral root development as well as regeneration.

plant biology↗
bioRxiv2021

Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individuals titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

immunology↗
bioRxiv2021

Automatic Detection and Neurotransmitter Prediction of Synapses in Electron Microscopy

This paper presents a deep-learning based workflow to detect synapses and predict their neurotransmitter type in the primitive chordate Ciona intestinalis (Ciona) EM images. Identifying synapses from electron microscopy (EM) images to build a full map of connections between neurons is a labor-intensive process and requires significant domain expertise. Automation of synapse detection and classification would hasten the generation and analysis of connectomes. Furthermore, inferences concerning neuron type and function from synapse features are in many cases difficult to make. Finding the connection between synapse structure and function is an important step in fully understanding a connectome. Activation maps derived from the convolutional neural network provide insights on important features of synapses based on cell type and function. The main contribution of this work is in the differentiation of synapses by neurotransmitter type through the structural information in their EM images. This enables prediction of neurotransmitter types for neurons in Ciona which were previously unknown. The prediction model with code is available on Github.

neuroscience↗
bioRxiv2021

Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity

Understanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics affects health outcomes. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The proposed KRV framework improves statistical power by capturing intrinsic structure within the genetic and microbiome data while reducing the multiple-testing burden. We apply the covariate-adjusted KRV test to the Hispanic Community Health Study/Study of Latinos in a genome-wide association analysis (first gene-level, then variant-level) for microbiome beta-diversity. We have identified an immunity-related gene, IL23R, reported in previous association studies and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. Our findings highlight the value of the KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition.

genomics↗
bioRxiv2021

Ionic strength modulates HU protein-induced DNA supercoiling

The histone-like protein from E. coli strain U93 (HU) is an abundant nucleoid-associated protein that contributes to the compaction of the bacterial genome as well as to the regulation of many of its transactions. Despite many years of investigations, the way and extent to which HU binding alters the DNA double helix and/or generates hierarchical structures using DNA as a scaffold is not completely understood. Here we combined single-molecule magnetic measurements with circular dichroism studies to monitor structural changes in the DNA-HU fiber as HU concentration was increased from 0 to 1000 nM under low and physiological monovalent salt conditions. We confirmed that DNA compaction correlated with HU concentration in a biphasic manner but DNA unwinding varied monotonically with HU concentration in 100 mM KCl. Instead, in more physiological 200 mM salt conditions, DNA compaction was monotonic while HU-induced DNA unwinding was negligible. Differential compaction and unwinding of DNA may be part of the response of bacteria to large variations in salt concentrations.

biophysics↗
bioRxiv2021

Batch effects removal for microbiome data via conditional quantile regression (ConQuR)

Batch effects in microbiome data arise from differential processing of specimens and can lead to spurious findings and obscure true signals. Most existing strategies for mitigating batch effects rely on approaches designed for genomic analysis, failing to address the zero-inflated and over-dispersed microbiome data. Strategies tailored for microbiome data are restricted to association testing, failing to allow other analytic goals such as visualization. We develop the Conditional Quantile Regression (ConQuR) approach to remove microbiome batch effects using a two-part quantile regression model. It is a fundamental advancement in the field because it is the first comprehensive method that accommodates the complex distributions of microbial read counts, and it generates batch-removed zero-inflated read counts that can be used in and benefit all usual subsequent analyses. We apply ConQuR to real microbiome data sets and demonstrate its state-of-the-art performance in removing batch effects while preserving or even amplifying the signals of interest.

bioinformatics↗
bioRxiv2021

Multiple in vivo roles for the C-terminal domain of the RNA chaperone Hfq

Hfq, a bacterial RNA chaperone, stabilizes small regulatory RNAs (sRNAs) and facilitates sRNA base-pairing with target mRNAs. Hfq has a conserved N-terminal domain and a poorly conserved disordered C-terminal domain (CTD). In a transcriptome-wide examination of the effects of a chromosomal CTD deletion (Hfq1-65), the Escherichia coli mutant was most defective for the accumulation of sRNAs that bind the proximal and distal faces of Hfq (Class II sRNAs), but other sRNAs also were affected. There were only modest effects on the levels of mRNAs, suggesting little disruption of sRNA-dependent regulation. However, cells expressing Hfq lacking the CTD deletion in combination with a weak distal face mutation were defective for the function of the Class II sRNA ChiX and repression of mutS, both dependent upon distal face RNA binding. Loss of the region between amino acids 66-72 was critical for this defect. The CTD region beyond amino acid 72 was not necessary for distal face-dependent regulation, but was needed for functions associated with the Hfq rim, seen most clearly in combination with a rim mutant. Our results suggest that the C-terminus collaborates in various ways with different binding faces of Hfq, leading to distinct outcomes for individual sRNAs.

microbiology↗
bioRxiv2021

σ28-dependent small RNAs regulate timing of flagella biosynthesis

Flagella are important for bacterial motility as well as for pathogenesis. Synthesis of these structures is energy intensive and, while extensive transcriptional regulation has been described, little is known about the posttranscriptional regulation. Small RNAs (sRNAs) are widespread posttranscriptional regulators, most base pairing with mRNAs to affect their stability and/or translation. Here we describe four UTR-derived sRNAs (UhpU, MotR, FliX and FlgO) whose expression is controlled by the flagella sigma factor {sigma}28 (fliA) in Escherichia coli. Interestingly, the four sRNAs have varied effects on flagellin protein levels, flagella number and cell motility. UhpU, corresponding to the 3 UTR of a metabolic gene, likely has hundreds of targets including a transcriptional regulator at the top flagella regulatory cascade connecting metabolism and flagella synthesis. Unlike most sRNAs, MotR and FliX base pair within the coding sequences of target mRNAs and act on ribosomal protein mRNAs connecting ribosome production and flagella synthesis. The study shows how sRNA-mediated regulation can overlay a complex network enabling nuanced control of flagella synthesis.

microbiology↗
bioRxiv2021

Untangling Microbiota Diversity and Assembly Patterns in the World's Largest Water Diversion Canal

Large water diversion projects are important constructions for reallocation of human-essential water resources. Deciphering microbiota dynamics and assembly mechanisms underlying canal water ecosystem services especially during long-distance diversion is the prerequisite for water quality monitoring, biohazard warning and sustainable management. Using a 1432-km canal of the South-to-North Water Diversion Projects as a model system, we answer three central questions: how bacterial and micro-eukaryotic communities spatio-temporally develop, how much ecological stochasticity contributes to microbiota assembly, and which immigrating populations better survive and navigate across the canal. We applied quantitative ribosomal RNA gene sequence analyses to investigate canal water microbial communities sampled over a year, as well as null model- and neutral model-based approaches to disentangle the microbiota assembly processes. Our results showed clear microbiota dynamics in community composition driven by seasonality more than geographic location, and seasonally dependent influence of environmental parameters. Overall, bacterial community was largely shaped by deterministic processes, whereas stochasticity dominated micro-eukaryotic community assembly. We defined a local growth factor (LGF) and demonstrated its innovative use to quantitatively infer microbial proliferation, unraveling taxonomically dependent population response to local environmental selection across canal sections. Using LGF as a quantitative indicator of immigrating capacities, we also found that most micro-eukaryotic populations (82%) from the source lake water sustained growth in the canal and better acclimated to the hydrodynamical water environment than bacteria (67%). Taxa inferred to largely propagate include Limnohabitans sp. and Cryptophyceae, potentially contributing to water auto-purification. Combined, our work poses first and unique insights into the microbiota assembly patterns and dynamics in the worlds largest water diversion canal, providing important ecological knowledge for long-term sustainable water quality maintenance in such a giant engineered system.

microbiology↗
bioRxiv2021

Single-dose respiratory mucosal delivery of next-generation viral-vectored COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2

The emerging SARS-CoV-2 variants of concern (VOC) increasingly threaten the effectiveness of current first-generation COVID-19 vaccines that are administered intramuscularly and are designed to only target the spike protein. There is thus a pressing need to develop next-generation vaccine strategies to provide more broad and long-lasting protection. By using adenoviral vectors (Ad) of human and chimpanzee origin, we developed Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens and evaluated them following single-dose intramuscular or intranasal immunization in murine models. We show that respiratory mucosal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the three-arm immunity, consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity. We further show that single-dose intranasal immunization provides robust protection against not only the ancestral strain of SARS-CoV-2, but also two emerging VOC, B.1.1.7 and B.1.351. Our findings indicate that single-dose respiratory mucosal delivery of an Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy against current and future VOC. This strategy has great potential to be used not only to boost first-generation vaccine-induced immunity but also to expand the breadth of protective T cell immunity at the respiratory mucosa.

immunology↗
bioRxiv2021

Repression of Hypoxia-Inducible Factor-1 Contributes to Increased Mitochondrial Reactive Oxygen Species Production in Diabetes

BackgroundExcessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. MethodsThe dynamic of ROS levels was analysed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia (ClinicalTrials.gov registration no. NCT02629406). The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes. ResultsExposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD) - dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1) and was followed by functional consequences. The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes. ConclusionsWe conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are highly significant and timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.

cell biology↗
bioRxiv2021

Embeddings of genomic region sets capture rich biological associations in lower dimensions

MotivationGenomic region sets summarize functional genomics data and define locations of interest in the genome such as regulatory regions or transcription factor binding sites. The number of publicly available region sets has increased dramatically, leading to challenges in data analysis. ResultsWe propose a new method to represent genomic region sets as vectors, or embeddings, using an adapted word2vec approach. We compared our approach to two simpler methods based on interval unions or term frequency-inverse document frequency and evaluated the methods in three ways: First, by classifying the cell line, antibody, or tissue type of the region set; second, by assessing whether similarity among embeddings can reflect simulated random perturbations of genomic regions; and third, by testing robustness of the proposed representations to different signal thresholds for calling peaks. Our word2vec-based region set embeddings reduce dimensionality from more than a hundred thousand to 100 without significant loss in classification performance. The vector representation could identify cell line, antibody, and tissue type with over 90% accuracy. We also found that the vectors could quantitatively summarize simulated random perturbations to region sets and are more robust to subsampling the data derived from different peak calling thresholds. Our evaluations demonstrate that the vectors retain useful biological information in relatively lower-dimensional spaces. We propose that vector representation of region sets is a promising approach for efficient analysis of genomic region data. Availabilityhttps://github.com/databio/regionset-embedding

bioinformatics↗
bioRxiv2021

DEPDC1/ EEF1A1 complex promotes the progression of human osteosarcoma via downregulation of FOXO3a

There are currently lack of effective therapeutic strategies for osteosarcoma, primarily due to insufficient understanding of the underlying mechanisms of the tumor cells. This study deciphers a potentially critical interplay of DEPDC1-EEF1A1-FOXO3a axis during the osteosarcoma progression. Bioinformatics analysis of documented 25,035 genes for differentially expressed genes were accompanied by transcriptional and translational examinations of clinical osteosarcoma specimens and osteosarcoma cell lines to assess the roles and interactions of DEP domain-containing 1 (DEPDC1), Elongation Factor 1-alpha 1 (EEF1A1), and FOXO3a in the tumor cells proliferation and prognosis. Gene expression profile analysis and clinical tests revealed highly expressed DEPDC1 in human osteosarcoma cells and tumor tissues. Vector-mediated silence of DEPDC1 resulted in halted osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Immunoprecipitation assay confirmed that EEF1A1 directly bind to DEPDC1 protein through three binding regions. Further, DEPDC1/EEF1A1 complex significantly decreased the expression of FOXO3a at transcription and translation levels, which subsequently promoted the proliferation of osteosarcoma cells and tumor metastasis. Correlation studies exhibited that overexpression of DEPDC1/EEF1A1 complex in the clinical specimens negatively correlated with the patient survival rate. In conclusion, DEPDC1-EEF1A1-FOXO3a axis plays as a critical pathway that regulates the progression and prognosis of osteosarcoma.

cell biology↗
bioRxiv2021

Effects of imidacloprid and thiamethoxam at LC30 and LC50 on the life table of soybean aphid Aphis glycines (Hemiptera: Aphididae)

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a main pests of soybean that poses a serious threat to its production. Studies were conducted to understand effects of the different concentrations of the insecticides (imidacloprid and thiamethoxam) on the life table of A. glycines to provide vital information for its effective management. We found that the mean generation time, adult and total pre-oviposition periods in A. glycines specimens exposed to LC50 imidacloprid and thiamethoxam were significantly longer than those in the control group. However, when exposed to LC30 imidacloprid and thiamethoxam, the adult pre-ovipositional period was significantly shorter than that in the control group. The mean fecundity per female adult, net reproductive rate, intrinsic rate of increase, and finite rate of increase were significantly decreased in individuals exposed to LC30 and LC50 concentrations of imidacloprid and thiamethoxam, respectively (P < 0.05). Both insecticides produce stress effects on A. glycines, and specimens treated with LC50 concentrations of the two insecticides exhibited a significant decrease in their growth rates than those treated with LC30 concentrations. This study provides data that can be used as a reference to predict the effect of imidacloprid and thiamethoxam on the population dynamics in the field, and agricultural producers could attach importance to prevent stimulation the reproduction made by low-lethal concentrations during actually applying pesticides.

pharmacology and toxicology↗
bioRxiv2021

piRNA pathway is essential for generating functional oocytes in golden hamster

Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that are critical for gametogenesis in various species. However, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals, and piRNA function in the oogenesis of other mammals has therefore remained elusive. Recent studies revealed the small RNA and PIWI transcriptional profiles in golden hamster oocytes more closely resemble that of humans than mice. Herein, we generated PIWIL1-, PLD6- and MOV10L1-deficient golden hamsters and found that all female mutants were sterile, with embryos arrested at the two-cell stage. In PIWIL1 mutant oocytes, we observed transposon accumulation and broad transcriptomic dysregulation, while zygotic gene activation was impaired in early embryos. Intriguingly, PIWIL1-piRNAs exhibited a unique, preferential silencing of endogenous retroviruses (ERVs), whereas silencing LINE1s depended on both PIWIL1- and PIWIL3-piRNAs. Moreover, we showed that piRNAs participate in the degradation of maternal mRNAs in MII oocytes and embryos via partially complementary targets. Together, our findings demonstrate that piRNAs are indispensable for generating functional oocytes in golden hamster, and show the informative value of this model for functional and mechanistic investigations of piRNAs, especially those related to female infertility.

developmental biology↗