Biology subjects

Zhou, Z.

Publications and source records attributed to Zhou, Z..

At least 307 records · Page 17Linked to original sources

bioRxiv2022

Heavy metal pollution characteristics of soil around a copper-nickel mine tailings pond in the northwest arid area of China and evaluation of desert phytoremediation potential

Phytoextraction and phytostabilization are two mechanisms used by plants to remove and stabilize heavy metals in soil. However, there has been little research on the extraction/stabilization of heavy metals by desert plants in arid areas. This study analyzed eight heavy metals (Cr, Ni, Cu, Zn, Cd, Pb, Mn, and As) in 10 desert plants and their growth matrices. In addition, the single factor pollution index and Nemerow comprehensive pollution index were used to evaluate soil pollution. Based on the biological accumulation factor and the biological concentration factor, the fuzzy evaluation method was used to evaluate plant extraction/stability potentials for heavy metals. The results showed that Cd, Cu, Ni, and Cr in the soil around the tailings pond were at the heavy pollution level, Mn and Pb pollution was moderate, and Zn and As pollution was light. The matrix factorization model showed that Cu and Ni came from industrial pollution; Cd and Cr came from atmospheric deposition and agricultural pollution; Pb came from traffic pollution; and Mn, Zn, and As came from natural sources. The metal contents of the desert plants exceeded the standard for normal plants, of which Cr contents in the Atriplex patens and Ammophila breviligulata Fernald aboveground parts were 35.63 and 53.77 mg/kg respectively, and the Ni contents in the Klasea centauroides subsp. polycephala (Iljin) L. Martins underground parts and the A. breviligulata Fernald aboveground parts were 102.67 and 101.67 mg/kg, respectively, exceeding the maximum toxicity threshold for Cr and Ni. Ammophila breviligulata Fernald had the highest plant comprehensive extraction coefficient (CEI) and plant comprehensive stability coefficient (CSI) at 0.81 and 0.83 respectively, indicating that it has strong heavy metal extraction and stabilization abilities. Therefore, A. breviligulata Fernald can be selected as a remediation species for heavy metal pollution in the soil around tailings reservoir areas.

ecology↗

bioRxiv2022

Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

Neanderthals were a species of archaic human that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding with the Neanderthals. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases. We hypothesized that genetic variants with strong detrimental effects on the function of the immune system could potentially contributed to the extinction of the Neanderthal population. In modern humans more than 450 genes are associated with inborn errors of immunity (IEI). We used the publically available genome information from a Neanderthal from the Altai mountains and filtered for potentially damaging variants that were present in genes associated with IEI, and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals. We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai Neanderthal. Interestingly, two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(Asn943Ser) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections. So, although we do not know exactly the functional impact yet, these three variants could have resulted in an increased susceptibility to severe diseases, and may have contributed to the extinction of Neanderthals after exposure to specific infections.

evolutionary biology↗

bioRxiv2022

DeepCIP: a multimodal deep learning method for the prediction of internal ribosome entry sites of circRNAs

MotivationCircular RNAs (circRNAs) have been found to have the potential to code proteins. Internal ribosome entry sites (IRESs) are key RNA regulatory elements for the translation of proteins by circRNAs through a cap-independent mechanism. IRES can be identified by bicistronic assay, but the method is time-consuming and laborious. Therefore, it is important to develop computational methods for facilitating IRES identification, evaluation, and design in circRNAs. ResultsIn this study, we proposed DeepCIP, a multimodal deep learning approach for circRNA IRES prediction, by exploiting both sequence and structure information. As far as we know, DeepCIP is the first predictor for circRNA IRESs, which consists of an RNA processing module, an S-LSTM module, a GCN module, a feature fusion module, and an ensemble module. The comparative studies show that DeepCIP outperforms other comparative methods and justify the effectiveness of the sequence model and structure model of DeepCIP for extracting features. We found that the integration of structural information on the basis of sequence information effectively improves predictive performance. For the real circRNA IRES prediction, DeepCIP also outperforms other methods. DeepCIP may facilitate the study of the coding potential of circRNAs as well as the design of circRNA drugs. DeepCIP as a standalone program is freely available at https://github.org/zjupgx/DeepCIP.

bioinformatics↗

bioRxiv2022

Nuclear autophagy interactome unveils WSTF as a constitutive nuclear inhibitor of inflammation

Macroautophagy (hereafter referred to as autophagy) degrades a variety of cellular components. A poorly understood area is autophagic degradation of nuclear substrates, or "nuclear autophagy". It remains unclear what can be degraded by autophagy from the mammalian nuclei. We began our study by investigating the nuclear binding partners of ATG8 family proteins that play important roles in recognizing autophagy substrates. We systematically evaluated the ATG8 nuclear interactome in primary human cells and in mouse brain, identifying hundreds of novel interactions. We continued our study by evaluating the nuclear proteomes of cellular senescence, a stable form of cell cycle arrest program associated with inflammation, in which nuclear autophagy is involved. Combined with the ATG8 nuclear interactome data, we identified WSTF, a component of the ISWI chromatin remodeling complex, as a novel substrate of nuclear autophagy. The degradation of WSTF, mediated by a direct interaction with the GABARAP isoform of ATG8, promotes chromatin accessibility of inflammatory genes and induces senescence-associated inflammation. Furthermore, WSTF directly binds the p65 subunit of NF-{kappa}B and inhibits its acetylation, thus blocking inflammatory gene expression in the setting of senescence, cancer, and pathogen infection. In addition, we show that loss of WSTF is required for the immuno-surveillance of oncogenic Ras in mouse liver; forced expression of WSTF inhibited tumor-suppressive inflammation and led to the development of liver tumors. Taken together, our study provides a global view of mammalian nuclear autophagy and reveals a novel nuclear inhibitor of inflammation implicated in diverse pathological contexts. Targeting WSTF may be broadly valuable as therapeutic intervention of inflammatory diseases.

cell biology↗

bioRxiv2022

Genetic, clinical underpinnings of subtle early brain change along Alzheimer's dimensions

Alzheimers disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised clustering technique known as Surreal-GAN, through which we identified two dominant dimensions of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE {varepsilon}4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained model in the general population and two cognitively unimpaired cohorts of asymptomatic participants. In the general population, genome-wide association studies found 77 genes unrelated to APOE differentially associated with R1 and R2. Functional analyses revealed that these genes were overrepresented in differentially expressed gene sets in organs beyond the brain (R1 and R2), including the heart (R1) and the pituitary gland, muscle, and kidney (R2). These genes were enriched in biological pathways implicated in dendritic cells (R2), macrophage functions (R1), and cancer (R1 and R2). Several of them were "druggable genes" for cancer (R1), inflammation (R1), cardiovascular diseases (R1), and diseases of the nervous system (R2). The longitudinal progression showed that APOE {varepsilon}4, amyloid, and tau were associated with R2 at early asymptomatic stages, but this longitudinal association occurs only at late symptomatic stages in R1. Our findings deepen our understanding of the multifaceted pathogenesis of AD beyond the brain. In early asymptomatic stages, the two dimensions are associated with diverse pathological mechanisms, including cardiovascular diseases, inflammation, and hormonal dysfunction - driven by genes different from APOE - which may collectively contribute to the early pathogenesis of AD.

bioengineering↗

bioRxiv2022

High Resolution Imaging of the Osteogenic and Angiogenic Interface at the Site of Cranial Bone Defect Repair via Multiphoton Microscopy

The spatiotemporal blood vessel formation and specification at the osteogenic and angiogenic interface of cranial bone defect repair were examined utilizing a high-resolution multiphoton-based imaging platform in conjunction with advanced optical techniques that allow interrogation of the oxygen microenvironment and cellular energy metabolism in living animals. Our study demonstrates the dynamic changes of vessel types, i.e. arterial, venous and capillary vessel networks at the superior and dura periosteum of cranial bone defect, suggesting a differential coupling of the vessel type with osteoblast expansion and bone tissue deposition/remodeling during repair. Employing transgenic reporter mouse models that label distinct types of vessels at the site of repair, we further show that oxygen distributions in capillary vessels at the healing site are heterogeneous as well as time and location-dependent. The endothelial cells coupling to osteoblasts prefer glycolysis and are less sensitive to microenvironmental oxygen changes than osteoblasts. In comparison, osteoblasts utilize relatively more OxPhos and potentially consume more oxygen at the site of repair. Taken together, our study highlights the dynamics and functional significance of blood vessel types at the site of defect repair, opening up opportunities for further delineating the oxygen and metabolic microenvironment at the interface of bone tissue regeneration.

bioengineering↗

bioRxiv2022

Bicistronic expression of a high-performance calcium indicator and opsin yields stable, robust cortical expression for holographic two-photon stimulation

Patterns of activity across many neurons are fundamental units of neural computation. Two-photon holographic photostimulation allows both delivering input to, and imaging responses from, patterns or populations of neurons. However, to make this method an easily-deployable tool, simple methods are needed to robustly and stably express opsins and indicators in the same cells. Here we describe a bicistronic adeno-associated virus (AAV) that in transfected cells expresses both the fast and bright calcium indicator GCaMP8s, and a soma-targeted (st) and two-photon-activatable opsin, ChrimsonR. With this method, in the visual cortex of mice, stChrimsonR stimulation with two-photon holography drives robust spiking in targeted cells, and neural responses to visual sensory stimuli and spontaneous activity are strong and easy to measure. stChrimsonR is a good choice of opsin when a balance is needed between stimulation-laser activatability and avoidance of imaging laser activation. This approach is a simple and robust way to prepare neurons in vivo for two-photon holography and imaging. Significance statementThe recent advent of holographic photostimulation methods in conjunction with standard two-photon calcium imaging promises unprecedented levels of control in manipulating and dissecting brain circuitry in vivo while reading out neural activity. These all-optical methods rely on a working synergy between optogenetic strategies to both measure calcium activity through genetically-encoded calcium indicators and modulate cell activity through light-activated opsins. Genetic strategies to achieve reliable and stable co-expression of opsin and indicator remain sparse and often challenging to execute. Here, we present a genetic tool to achieve robust co-expression of jGCaMP8s indicator and stChrimsonR opsin via a single injected virus to help facilitate experiments aiming to use holography to investigate the circuit principles underlying brain activity.

neuroscience↗

bioRxiv2022

Excitation creates a distributed pattern of cortical suppression due to varied recurrent input

Dense local, recurrent connections are a major feature of cortical circuits, yet how they affect neurons responses is unclear, with some studies reporting weak recurrent effects, some amplification, and others showing instead local suppression. Here, we show that optogenetic input to mouse V1 excitatory neurons generates salt-and-pepper patterns of both excitation and suppression. Responses in individual neurons are not strongly predicted by that neurons direct input. A balanced-state network model reconciles a set of diverse observations: the observed dynamics, suppressed responses, decoupling of input and output, and long tail of excited responses. The model shows recurrent excitatory-excitatory connections are strong and also variable across neurons. Together, these results demonstrate that excitatory recurrent connections can have major effects on cortical computations, by shaping and changing neurons responses to input.

neuroscience↗

bioRxiv2022

MMP14 cleaves PTH1R in the chondrocyte derived osteoblast lineage, curbing signaling intensity for proper bone anabolism

Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, HC descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, HC lineage-specific Mmp14 null mutants (Mmp14{Delta}HC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling and PTH signaling is enhanced in Mmp14{Delta}HC mutants. We found HC-derived osteoblasts contribute [~]50% of osteogenesis promoted by treatment with PTH 1-34 and this response was amplified in Mmp14{Delta}HC. MMP14 control of PTH signaling likely applies also to both HC- and non- HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated titration of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.

developmental biology↗

bioRxiv2022

Global patterns of diversity and metabolism of microbial communities in deep-sea hydrothermal vent deposits

BackgroundWhen deep-sea hydrothermal fluids mix with cold oxygenated fluids, minerals precipitate out of solution and form hydrothermal deposits. These actively venting deep-sea hydrothermal vent deposits support a rich diversity of thermophilic microorganisms which are involved in a range of carbon, sulfur, nitrogen, and hydrogen metabolisms. Global patterns of thermophilic microbial diversity in deep-sea hydrothermal ecosystems have illustrated the strong connectivity between geological processes and microbial colonization, but little is known about the genomic diversity and physiological potential of these novel taxa. Here we explore this genomic diversity in 42 metagenomes from four deep-sea hydrothermal vent fields and a deep-sea volcano collected from 2004 to 2018, and document their potential implications in biogeochemical cycles. ResultsOur dataset represents 3,635 metagenome-assembled genomes encompassing 511 novel genera, with 395 Bacteria and 116 Archaea, providing many targets for cultivation of novel archaeal and bacterial families. Notably, 52% (206) of the novel bacterial genera and 72% (84) of the novel archaeal genera were found at the deep-sea Brothers volcano, many of which were endemic to the volcano. We report some of the first examples of medium to high-quality MAGs from phyla and families never previously identified, or poorly sampled, from deep-sea hydrothermal environments. We greatly expand the novel diversity of Thermoproteia, Patescibacteria (Candidate Phyla Radiation, CPR), and Chloroflexota found at deep-sea hydrothermal vents and identify a small sampling of two potentially novel phyla, designated JALSQH01 and JALWCF01. Metabolic pathway analysis of metagenomes provides insights into the prevalent carbon, nitrogen, sulfur and hydrogen metabolic processes across all sites, and illustrates sulfur and nitrogen metabolic handoffs in community interactions. We confirm that Campylobacteria and Gammaproteobacteria occupy similar ecological guilds but their prevalence in a particular site is driven by shifts in the geochemical environment. ConclusionOur study of globally-distributed hydrothermal vent deposits provides a significant expansion of microbial genomic diversity associated with hydrothermal vent deposits and highlights the metabolic adaptation of taxonomic guilds. Collectively, our results illustrate the importance of comparative biodiversity studies in establishing patterns of shared phylogenetic diversity and physiological ecology, while providing many targets for enrichment and cultivation of novel and endemic taxa.

microbiology↗

bioRxiv2022

TSNAdb v2.0: the updated version of tumor-specific neoantigen database

Tumor neoantigens have been well-acknowledged as ideal targets for tumor immunotherapy in recent years. With the deepening of research on neoantigen-based tumor immunotherapy, comprehensive neoantigen databases are urgently needed to meet the growing demand for clinical studies. We have built the Tumor-Specific NeoAntigen Database (TSNAdb v1.0) previously, which has attracted wide attention. In this study, we provide an updated version of the Tumor-Specific NeoAntigen Database (TSNAdb v2.0) with several new features including 1) taking stricter criteria for neoantigen identification. 2) providing predicted neoantigens derived from three types of somatic mutations. 3) collecting experimentally validated neoantigens and classifying them according to the evidence. TSNAdb v2.0 is freely available at https://pgx.zju.edu.cn/tsnadb/.

bioinformatics↗

bioRxiv2022

Multiscale functional connectivity patterns of the aging brain learned from rsfMRI data of 4,259 individuals of the multi-cohort iSTAGING study

To learn multiscale functional connectivity patterns of the aging brain, we built a brain age prediction model of functional connectivity measures at seven scales on a large fMRI dataset, consisting of resting-state fMRI scans of 4259 individuals with a wide age range (22 to 97 years, with an average of 63) from five cohorts. We computed multiscale functional connectivity measures of individual subjects using a personalized functional network computational method, harmonized the functional connectivity measures of subjects from multiple datasets in order to build a functional brain age model, and finally evaluated how functional brain age gap correlated with cognitive measures of individual subjects. Our study has revealed that functional connectivity measures at multiple scales were more informative than those at any single scale for the brain age prediction, the data harmonization significantly improved the brain age prediction performance, and harmonization in the tangent space worked better than in the original space. Moreover, brain age gap scores of individual subjects derived from the brain age prediction model were significantly correlated with clinical and cognitive measures. Overall, these results demonstrated that multiscale functional connectivity patterns learned from a large-scale multi-site rsfMRI dataset were informative for characterizing the aging brain and the derived brain age gap was associated with cognitive and clinical measures.

bioengineering↗

bioRxiv2022

Insight into the evolutionary assemblage of cranial kinesis from a Cretaceous bird

The independent movements and flexibility of various parts of the skull, called cranial kinesis, is an evolutionary innovation that is found in living vertebrates only in some squamates and crown birds, and considered to be a major factor underpinning much of the enormous phenotypic and ecological diversity of living birds, the most diverse group of extant amniotes. Compared to the postcranium, our understanding of the evolutionary assemblage of the characteristic modern bird skull has been hampered by sparse fossil records of early cranial materials, with competing hypotheses regarding the evolutionary development of cranial kinesis among early members of the avialans. Here, a detailed three-dimensional reconstruction of the skull of the Early Cretaceous enantiornithine Yuanchuavis kompsosoura allows for its in depth description, including elements that are poorly known among early diverging avialans but are central to deciphering the mosaic assembly of features required for modern avian cranial kinesis. Our reconstruction of the skull shows evolutionary and functional conservation of the temporal and palatal regions by retaining the ancestral theropod dinosaurian configuration within the skull of this otherwise derived and volant bird. Geometric morphometric analysis of the palatine suggests that loss of the jugal process represents the first step in the structural modifications of this element leading to the kinetic crown bird condition. The mixture of plesiomorphic temporal and palatal structures together with a derived avialan rostrum and postcranial skeleton encapsulated in Yuanchuavis manifests the key role of evolutionary mosaicism and experimentation in early bird diversification.

paleontology↗

bioRxiv2022

Self-cyclisation as a general and efficient platform for peptide and protein macrocyclisation

Macrocyclisation of proteins and peptides results in a remarkable increase in structural stability, making cyclic peptides and proteins of great interest in drug discovery--either directly as drug leads or as in the case of cyclised nanodiscs (cNDs), as tools for studies of trans-membrane receptors and membrane-active peptides. Various biological methods have been developed that are capable of yielding head-to-tail macrocyclised products. Such enzymatic methods require careful optimisation of cyclisation over polymerisation. Here, we describe the engineering of self-cyclising "autocyclase" proteins, where an intramolecular rearrangement can be triggered to yield a monomeric cyclic product in high yields. We characterise the self-cyclisation reaction mechanism and demonstrate how the unimolecular reaction path can circumvent existing challenges of enzymatic cyclisation. We use the method to produce several notable cyclic peptides and proteins, demonstrating how autocyclases offer a simple and scalable way to access a vast diversity of macrocyclic biomolecules.

biochemistry↗

bioRxiv2022

Amplified cortical neural responses as animals learn to use novel activity patterns

Cerebral cortex supports representations of the world in patterns of neural activity, used by the brain to make decisions and guide behavior. Past work has found diverse, or limited, changes in the primary sensory cortex in response to learning, suggesting the key computations might occur in downstream regions. Alternatively, sensory cortical changes may be central to learning. We studied cortical learning by using controlled inputs we insert: we trained mice to recognize entirely novel, non-sensory patterns of cortical activity in the primary visual cortex (V1) created by optogenetic stimulation. As animals learned to use these novel patterns, we found their detection abilities improved by an order of magnitude or more. The behavioral change was accompanied by large increases in V1 neural responses to fixed optogenetic input. Neural response amplification to novel optogenetic inputs had little effect on existing visual sensory responses. A recurrent cortical model shows that this amplification can be achieved by a small mean shift in recurrent network synaptic strength. Amplification would seem to be desirable to improve decision-making in a detection task, and therefore these results suggest that adult recurrent cortical plasticity plays a significant role in improving behavioral performance during learning.

neuroscience↗

bioRxiv2022

Metabolite annotation from knowns to unknowns through knowledge-guided multi-layer metabolic network

Liquid chromatography - mass spectrometry (LC-MS) based untargeted metabolomics allows to measure both known and unknown metabolites in the metabolome. However, unknown metabolite annotation is a grand challenge in untargeted metabolomics. Here, we developed an approach, namely, knowledge-guided multi-layer network (KGMN), to enable global metabolite annotation from knowns to unknowns in untargeted metabolomics. The KGMN approach integrated three-layer networks, including knowledge-based metabolic reaction network, knowledge-guided MS/MS similarity network, and global peak correlation network. To demonstrate the principle, we applied KGMN in an in-vitro enzymatic reaction system and different biological samples, with [~]100-300 putative unknowns annotated in each data set. Among them, >80% unknown metabolites were validated with in-silico MS/MS tools. Finally, we successfully validated 5 unknown metabolites through the repository-mining and the syntheses of chemical standards. Together, the KGMN approach enables efficient unknown annotations, and substantially advances the discovery of recurrent unknown metabolites towards deciphering dark matters in untargeted metabolomics.

bioinformatics↗

bioRxiv2022

The sulfur cycle connects microbiomes and biogeochemistry in deep-sea hydrothermal plumes

In globally distributed deep-sea hydrothermal vent plumes, microbiomes are shaped by the redox energy landscapes created by reduced hydrothermal vent fluids mixing with oxidized seawater. Plumes can disperse over thousands of kilometers and are complex. Their characteristics are determined by geochemical sources from hydrothermal vents, e.g., hydrothermal inputs, nutrients, and trace metals. However, the impacts of plume biogeochemistry on the oceans are poorly constrained due to a lack of integrated understanding of microbiomes, population genetics, and geochemistry. Here, we use microbial genomes to understand links between biogeography, evolution, and metabolic connectivity, and elucidate their impacts on biogeochemical cycling in the deep sea. Using data from 37 diverse plumes from 8 ocean basins, we show that sulfur metabolism defines the core microbiome of plumes and drives metabolic connectivity. Amongst all microbial metabolisms, sulfur transformations had the highest MW-score, a measure of metabolic connectivity in microbial communities. Our findings provide the ecological and evolutionary basis of change in sulfur-driven microbial communities and their population genetics in adaptation to changing geochemical gradients in the oceans.

microbiology↗

bioRxiv2022

MATTE: anti-noise module alignment for phenotype-gene-related analysis

PurposeAlthough many transcriptome analysis methods find fundamental interactions or markers of some phenotypes, preservation of module or network is still a challenge. MethodsThe study developed a method to directly compare the transcriptome data of phenotypes and present the differences modularly, called Module Alignment of TranscripTomE(MATTE). ResultsMATTE performs better under high noise than differential co-expression(DC) clustering in the simulation experiments but still detects differential expression(DE) and DC genes. After subsequent annotation of cell types in single-cell data, MATTE obtained the best scores in both supervised and unsupervised learning, i. e. MATTE found meaningful markers. Finally, we apply MATTE in analyzing the transcriptome of Breast Cancer(BRCA). We have found five BRCA subtypes, and the characteristic of one subtype is detected in the form of a module network. ConclusionMATTE can find meaningful genes and modules, thus facilitating the downstream analysis task to obtain insight into biology.

bioinformatics↗