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Biology subjects

Zhang, M.

Publications and source records attributed to Zhang, M..

At least 757 records · Page 42Linked to original sources

Retrieval Practice Facilitates Judgments of Learning Through Multiple Mechanisms

Prior studies have shown that predictions of subsequent performance (i.e., Judgments of Learning, JoLs) following practice tests are more accurate than those following re-study. The majority of studies have suggested that retrieval practice allows people to base their predictions on the current retrieval outcomes so that they assign a higher likelihood of remembering the answers with high confidence. We speculated that other information made available through retrieval practice might also be important for JoLs. In the present study, we asked participants to study word pairs and undergo either a practice test or re-study. Two testing formats (cued-recall and multiple choice) were administrated for practice tests in two separate experiments. After each practice trial, participants rated their confidence in the current retrieval accuracy (test) or confidence in acquisition (re-study), followed by a JoL rating where participants predicted their performance in the final test one day later. The results of both experiments showed that the correlation between JoL ratings and the final accuracy was higher for trials practiced with testing. Moreover, using mediation analyses, we found that this high correspondence was only partially mediated by participants confidence in practice tests. More importantly, the reaction time of retrieval also significantly mediated the correspondence between JoLs and the final accuracy, suggesting that participants were able to correctly base their JoLs on multiple sources of information that is made available through retrieval practice. We conclude that practice testing benefits JoLs through multiple mechanisms.

neuroscience↗

Silicone oil-induced ocular hypertension in mouse models glaucomatous neurodegeneration and neuroprotection

Understanding the molecular mechanism of glaucoma and development of neuroprotectants are significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. We observed similar intraocular pressure (IOP) elevation after intracameral injection into mouse eyes of SO, and removing the SO allows the IOP level to quickly return to normal. This simple, inducible and reversible mouse model showed dynamic changes of visual function that correlate with progressive RGC loss and axon degeneration. We also used a single AAV vector for the first time to co-express miRNA-based shRNA and a neuroprotective transgene and further validated this model as an effective in vivo means to test neuroprotective therapies by targeting neuronal endoplasmic reticulum stress.

neuroscience↗

A Novel Neoantigen Discovery Approach based on Chromatin High Order Conformation: Mapping the Neoantigen to 3D Genome

The high-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate immune response of the T cells. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Here we retrospect the DNA origins of the immune-positive and non-negative neoantigens in the context of 3D genome and discovered that 1) DNA loci of the immuno-positive neoantigens tend to cluster genome-wise. 2) DNA loci of the immuno-positive neoantigens tend to belong to active chromosomal compartment (compartment A) in some chromosomes. 3). DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We believe that the 3D genome information will help more precise neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

bioinformatics↗

Incorporating prior information into signal-detection analyses across biologically informed gene-sets

Signal detection analyses are used to assess whether there is any evidence of signal within a large collection of hypotheses. For example, we may wish to assess whether there is any evidence of association with disease among a set of biologically related genes. Such an analysis typically treats all genes within the sets similarly, even though there is substantial information concerning the likely importance of each gene within each set. For example, deleterious variants within genes that show evidence of purifying selection are more likely to substantially affect the phenotype than genes that are not under purifying selection, at least for traits that are themselves subject to purifying selection. Here we improve such analyses by incorporating prior information into a higher-criticism-based signal detection analysis. We show that when this prior information is predictive of whether a gene is associated with disease, our approach can lead to a significant increase in power. We illustrate our approach with a gene-set analysis of amyotrophic lateral sclerosis (ALS), which implicates a number of gene-sets containing SOD1 and NEK1 as well as showing enrichment of small p-values for gene-sets containing known ALS genes.

genetics↗

Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank

Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large sample without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 quantitative traits in the UK Biobank, and identified 75 significant vQTLs with P<2.0x10-9 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.

genetics↗

Depression and Anxiety in Healthcare Staffs in A Tertiary University Hospital in Luoyang, Henan Province: A Cross-Sectional Observational Study

Abstract ObjectiveMental health condition of medical professionals in China is under-recognized. The current study aimed to determine the prevalence of depression and anxiety among healthcare professionals and explore the potential influence factors.\n\nMethodThe study employed a cross-sectional design. All employees were surveyed in the first week of September 2017. General information included gender, age, workload, workplace violence, sleep quality and so on. Depression and anxiety were evaluated using PHQ-9 and GAD-7, respectively. SPSS 22.0 was used for data analysis. Logistic regression was conducted to explore risk factors contributed to metal health.\n\nResultsA total of 1,950 questionnaires were delivered, and 1,864 were returned with a response rate of 95.6%. The prevalence of depression and anxiety were 24.1% and 28.9%. As for workload, the average number of beds in charge per month is 65.97{+/-}95.58 beds, among which internal medicine department and surgical department endure more workloads. Though workers in ER and ICU manage fewer beds, they bear the longest nonstop working length in the previous month (19.18{+/-}10.82 h). There were 78.0% had suffered WPV in the preceding year. Staffs in ER and ICU are at higher risk to physical violence, especially doctors. Regarding to sleep quality, only 9.2% participants reported that they sleep well. Logistic regression indicated that workplace violence and sleep quality were independent risk factors for both anxiety and depression.\n\nConclusionThe current study revealed the devastating conditions of mental disorders in medical workers and associated factors. Effective interventions are necessary to improve this situation.

scientific communication and education↗

Integrative methylome and transcriptome analysis of Japanese flounder (Paralichthys olivaceus) skeletal muscle during development

DNA methylation is an important epigenetic modification in vertebrate and is essential for epigenetic gene regulation in skeletal muscle development. We showed the genome-wide DNA methylation profile in skeletal muscle tissue of larval 7dph (JP1), juvenile 90dph (JP2), adult female 24 months (JP3) and adult male 24 months (JP4) Japanese flounder. The distribution and levels of methylated DNA within genomic features (1stexons, gene body, introns, TSS200, TSS1500 and intergenic) show different developmental landscapes. We also successfully identified differentially methylated regions (DMRs) and different methylated genes (DMGs) through a comparative analysis, indicating that DMR in gene body, intron and intergenic regions were more compared to other regions of all DNA elements. A gene ontology analysis indicated that the DMGs were mainly related to regulation of skeletal muscle fiber development process, Axon guidance, Adherens junction, and some ATPase activity. Methylome and transcriptome clearly revealed a exhibit a negative correlation. And integration analysis revealed a total of 425, 398 and 429 negatively correlated genes with methylation in the JP2_VS_JP1, JP3_VS_JP1 and JP4_VS_JP1 comparison groups, respectively. And these genes were functionally associated with pathways including Adherens junction, Axon guidance, Focal adhesion, cell junctions, Actin cytoskeleton and Wnt signaling pathways. In addition, we validated the MethylRAD results by bisulfite sequencing PCR (BSP) in some of the differentially methylated skeletal muscle growth-related genes (Myod1, Six1 and Ctnnb1). In this study, we have generated the genome-wide profile of methylome and transcriptome in Japanese flounder for the first time, and our results bring new insights into the epigenetic regulation of developmental processes in Japanese flounder. This study contributes to the knowledge on epigenetics in vertebrates.\n\nAuthor summaryEpigenetic mechanisms like DNA methylation have recently reported as vital regulators of some species skeletal muscle development through the control of genes related to growth. To date, although genome-wide DNA methylation profiles of many organisms have been reported and the Japanese flounder reference genome and whole transcriptome data are publically available, the methylation pattern of Japanese flounder skeletal muscle tissue remains minimally studied and the global DNA methylation data are yet to be known. Here we investigated the genome-wide DNA methylation patterns in Japanese flounder, throughout its development. These findings help to enrich research in molecular and developmental biology in vertebrates.

epidemiology↗

Genomic approaches reveal an endemic sub-population of gray wolves in Southern China

Despite being one of the most widely distributed terrestrial mammals, the history of gray wolves (Canis lupus) in China is not well understood as their habitats have been destroyed with growing economic development. Using six specimens from wolf skins in Chinese Natural History museums, we sequenced their genome using a modified ancient DNA procedure. Using whole genome sequence analysis, we showed that gray wolves from Southern China (SC) derive from a single lineage, distinct from gray wolves from the Tibetan Plateau (Canis lupus chanco) and Northern China, suggesting that SC gray wolves may form a distinct sub-population. Of SC gray wolves, one wolf from Zhejiang carries a genetic component from a canid that must have diverged earlier from other wolves than jackals did, perhaps through gene flow from a population related to or further diverged from wolves than the dhole, a species distributed in Southern China and Southeast Asia. This may indicate that interspecific gene flow likely played an important role in shaping the speciation patterns and population structure in the genus Canis. Our study is the first to survey museum genomes of gray wolves from Southern China, revealing the presence of an endemic population with ancient interspecific gene flow from a population related to the dhole, and highlighting how sequencing the paleogenome from museum specimens can help us to study extinct species.

evolutionary biology↗

LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization

Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages (BMDMs). Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization related gene IFN-{gamma} was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization and will provide new insights for immunotherapy in macrophage-associated diseases.

cell biology↗

The BD2 domain of BRD4 is a determinant in EndoMT and vein graft neointima formation

BackgroundVein-graft bypass is commonly performed to overcome atherosclerosis but is limited by high failure rates, principally due to neointimal wall thickening. Recent studies reveal that endothelial-mesenchymal transition (EndoMT) is critical for vein-graft neointima formation. BETs are a family of Bromo/ExtraTerminal domains-containing epigenetic reader proteins (BRD2, BRD3, BRD4). They bind acetylated histones through their unique tandem bromodomains (BD1, BD2), facilitating transcriptional complex formation and cell-state transitions. The role for BETs, including individual BRDs and their unique BDs, is not well understood in EndoMT and neointimal formation.\n\nMethods and ResultsRepression of BRD4 expression abrogated TGF{beta}1-induced EndoMT, with greater effects than BRD2 or BRD3 knockdown. An inhibitor selective for BD2 in all BETs, but not that for BD1, blocked EndoMT. Moreover, expression of a dominant-negative BRD4-specific BD2 fully abolished EndoMT. Concordantly, BRD4 knockdown repressed TGF{beta}1-stimulated increase of ZEB1 protein - a transcription factor integral in EndoMT. In vivo, lentiviral gene transfer of either BRD4 shRNA or dominant negative BRD4-specific BD2 mitigated neointimal development in rat jugular veins grafted to carotid arteries.\n\nConclusionsOur data reveal the BD2 domain of BRD4 as a determinant driving EndoMT in vitro and neointimal formation in vivo. These findings provide new insight into BET biology, while offering prospects of specific BET domain targeting as an approach to limiting neointima and extending vein graft patency.

pathology↗

Professional Swimmers and Normal Populations have Different Patterns of Epidermal Green Autofluorescence

Our recent studies have suggested that green autofluorescence of the fingernails and certain regions of skin may be novel biomarkers for disease diagnosis and evaluation of the injury state of cardiovascular system. Our study has also suggested that oxidative stress may produce the increased epidermal green AF by altering keratin 1. Since athletes body may have increased oxidative stress and inflammation, we proposed our hypothesis that athletes may have increased green AF in their fingernails and certain regions of their skin. In current study we tested this hypothesis by determining the green AF of professional swimmers. We found that compared with age-matched controls, both the green AF intensity and AF asymmetry in both right and left antebrachium and Ventriantebrachium of the professional swimmers is significantly higher. In left Dorsal Centremetacarpus, the green AF intensity of the professional swimmers is significantly higher than that of the age-matched controls. In contrast, the green AF intensity or AF asymmetry of the professional swimmers is not significantly different from that of the age-matched controls in Centremetacarpus, Ventroforefinger, Dorsal Index Finger and Index Fingernails. Collectively, our study has provided first evidence suggesting that athletes have increased green AF intensity and asymmetry in certain regions of their skin. Based on this finding, we may evaluate non-invasively the levels of oxidative damage and inflammation in athletes body.

biophysics↗

The green autofluorescence intensity and asymmetry of older men is significantly higher than those of older women in their fingernails and certain regions of skin

Our recent studies have suggested that the patients of multiple diseases have characteristic Pattern of Autofluorescence (AF) in their skin and fingernails, which may become novel biomarkers for both disease diagnosis and evaluation of health state. Since male populations may have higher levels of oxidative stress and inflammation than female population, in our current study we tested our hypothesis that the green AF intensity of older men is higher than that of older women in their fingernails and skin. We found that in both left and right Index Fingernails, the green AF intensity of the men of both the age group of 61 - 70 years of old and the age group of 71 - 80 years of old is significantly higher than that of the women of the same age groups. At both left Dorsal Centremetacarpus and left Centremetacarpus, the green AF intensity of the men at the age between 71 - 80 years of old is also significantly higher than that of the women of the same age group. Moreover, in Index Fingernails, Dorsal Centremetacarpus and Centremetacarpus, the green AF asymmetry of the older men of certain age groups is significantly higher than that of the women of the same age groups. Collectively, our study has provided the first evidence indicating the gender difference between the green AF intensity and asymmetry of older men and those of older women in their fingernails and certain regions of skin, which is valuable for establishing the AF-based diagnostic method.

biophysics↗

The third-generation tetracycline, KBP-7072, exploits and reveals a new potential of the primary tetracycline binding pocket

Antibiotic resistance is a growing threat to human health requiring the discovery or development of new anti-infectives. As such, KBP-7072 is a novel tetracycline derivative that exhibits broad-spectrum activity against Gram-positive and -negative bacterial strains. To determine the mechanism of action of KBP-7072 and understand how its unique C9 extension can be used to combat the growing problem of antibiotic resistance we determined the structure of KBP-7072 bound to the bacterial 30S ribosomal subunit, the inhibitory target of typical tetracyclines. We show that KBP-7072 binds to the primary tetracycline binding site on the 30S ribosomal subunit consistent with it acting as a protein synthesis inhibitor that blocks A-site occupation. Moreover, the unique chemical nature of KBP-7072{acute}s C9 extension leads to a distinctive interaction pattern with the 30S subunit that distinguishes KBP-7072 from the third-generation tetracycline, Tigecycline, and thus expands the interaction potential of the primary tetracycline binding pocket.

biochemistry↗

Computational Correction of Spatially-Variant Optical Aberrations in 3D Single Molecule Localization Microscopy

3D single-molecule localization microscopy relies on fitting the shape of point-spread-functions (PSFs) recorded on a wide-field detector. However, optical aberrations distort those shapes, which compromise the accuracy and precision of single-molecule localization microscopy. Here we employ a computational phase retrieval based on a vectorial PSF model to quantify the spatially-variance of optical aberrations in a two-channel ultrawide-field single-molecule localization microscope. The use of a spatially-variant PSF model enables accurate and precise emitter localization in x, y- and z-directions throughout the entire field-of-view.\n\nOCIS Codes(100.6640) Superresolution; (180.2520) Fluorescence microscopy; (180.6900) Three-dimensional microscopy; (100.5070) Phase retrieval; (150.1135) Algorithms; (220.1010) Aberrations (global).

biophysics↗

Lipopolysaccharide (LPS) induces increased epidermal green autofluorescence of mouse

Our recent studies have suggested that characteristic Pattern of Autofluorescence (AF) of each disease could be a novel biomarker for non-invasive diagnosis of multiple major diseases such as acute ischemic stroke. It is necessary to determine if increased epidermal green AF may be produced by major pathological factors such as inflammation. In our current study, we used C57BL/6Slac mice exposed to LPS to test our hypothesis that inflammation may induce increased epidermal green AF: LPS rapidly induced significant increases in the epidermal green AF of the mices ears at 1 hr after LPS injection. LPS also dose-dependently increased the epidermal green AF. The AF intensity had a linear relationship with the LPS dosages at both 3 and 7 days after the LPS administration. The AF images exhibited the characteristic structure of the keratinocytes in Stratum Spinosum, suggesting that the origin of the increased AF was keratin 1 and/or keratin 10. Collectively, our current study has provided the first evidence indicating that inflammation can rapidly and dose-dependently induce increased epidermal green AF, suggesting that the green AF may be the first biomarker for non-invasive and rapid detection of systemic inflammation. Since inflammation is a key pathological factor of numerous diseases, our finding has highlighted the value of the epidermal AF as a novel diagnostic biomarker for numerous diseases.

biophysics↗

The rice G protein γ subunit qPE9-1 positively regulates grain-filling process by interacting with abscisic acid and auxin

The rice genome contains a single G (RGA1) and G{beta} (RGB1) and five G{gamma} subunits. Recent genetic studies have shown that DEP1/qPE9-1, an atypical putative G{gamma} protein, is responsible for dense and erect panicles, but the biochemical and molecular mechanisms underlying control of grain size are not well understood. Here, we report that plants carrying qPE9-1 have more endosperm cells per grain than plants contain the qpe9-1 allele. The qPE9-1 line has a higher rate and longer period of starch accumulation than the qpe9-1 line. Additionally, the expression of several key genes encoding enzymes catalyzing sucrose metabolism and starch biosynthesis is higher in the qPE9-1 line than in the qpe9-1 line, especially from the mid to late grain-filling stage. Grains of the qPE9-1 line also have higher contents of two phytohormones, ABA and IAA. Exogenous application of ABA or IAA enhanced starch accumulation and the expression of genes encoding grain-filling-related enzymes in the grains of qPE9-1, whereas only IAA produced these effects in qpe9-1. Based on these results, we conclude that qPE9-1 promotes endosperm cell proliferation and positively regulates starch accumulation largely through ABA and IAA, which enhance the expression of genes encoding starch biosynthesis during the late grain-filling stage.

plant biology↗

Bayesian Shrinkage Estimation of High Dimensional Causal Mediation Effects in Omics Studies

Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high-throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of omics data, joint analysis of molecular-level genomics data with epidemiological data through mediation analysis is becoming more common. However, such joint analysis requires methods that can simultaneously accommodate high-dimensional mediators and that are currently lacking. To address this problem, we develop a Bayesian inference method using continuous shrinkage priors to extend previous causal mediation analysis techniques to a high-dimensional setting. Simulations demonstrate that our method improves the power of global mediation analysis compared to simpler alternatives and has decent performance to identify true non-null mediators. We also construct tests for natural indirect effects using a permutation procedure. The Bayesian method helps us to understand the structure of the composite null hypotheses. We applied our method to Multi-Ethnic Study of Atherosclerosis (MESA) and identified DNA methylation regions that may actively mediate the effect of socioeconomic status (SES) on cardiometabolic outcome.

epidemiology↗

Functional network dynamics in a neurodevelopmental disorder of known genetic origin

Cognitive processing depends on the temporal co-ordination of functional brain networks. This fundamental aspect of neurophysiology potentially bridges the genetic regulation of neuronal activity and developmental cognitive impairments. We investigated brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with ZDHHC9-associated intellectual disability to individuals with no known impairment. We used Hidden Markov Modelling on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation, to characterise transient network dynamics. At rest, network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation. Crucially, ZDHHC9 gene expression levels predicted the group differences across networks, supporting an association between molecular pathology and neurophysiology. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between brain network dynamics and regional gene expression, and present a valuable method for understanding the real-time neural mechanisms linking genetic variation to cognitive difficulties.

neuroscience↗