Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 1,495 records · Page 83Linked to original sources

bioRxiv2019

Genome-wide variations analysis of special waxy sorghum cultivar Hongyingzi for brewing Moutai liquor

AbstractsHongyingzi is a special waxy sorghum (Sorghum bicolor L. Moench) cultivar for brewing Moutai liquor. For an overall understanding of the whole genome of Hongyingzi, we performed whole-genome resequencing technology with 56.10 X depth to reveal its comprehensive variations. Compared with the BTx623 reference genome, 2.48% of genome sequences were altered in the Hongyingzi genome. Among these alterations, there were 1885774 single nucleotide polymorphisms (SNPs), 309381 small fragments insertions and deletions (Indels), 31966 structural variations (SVs), and 217273 copy number variations (CNVs). These alterations conferred 29614 genes variations. It was also predicted that 35 genes variations were related to the multidrug and toxic efflux (MATE) transporter, chalcone synthase (CHS), ATPase isoform 10 (AHA10) transporter, dihydroflavonol-4-reductase (DFR), the laccase 15 (LAC15), flavonol 3'-hydroxylase (F3'H), flavanone 3-hydroxylase (F3H), O-methyltransferase (OMT), flavonoid 3'5' hydroxylase (F3'5'H), UDP-glucose:sterol-glucosyltransferase (SGT), flavonol synthase (FLS), and chalcone isomerase (CHI) involved in the tannin synthesis. These results would provide theoretical supports for the molecular markers developments and gene function studies related to the liquor-making traits, and the genetic improvement of waxy sorghum based on the genome editing technology.

genomics↗

bioRxiv2019

Identification of a small molecule that stimulates human beta-cell proliferation and insulin secretion, and protects against cytotoxic stress in rat insulinoma cells

A key event in the development of both major forms of diabetes is the loss of functional pancreatic islet {beta}-cell mass. Strategies aimed at enhancing {beta}-cell regeneration have long been pursued, but methods for reliably inducing human {beta}-cell proliferation with full retention of key functions such as glucose-stimulated insulin secretion (GSIS) are still very limited. We have previously reported that overexpression of the homeobox transcription factor Nkx6.1 stimulates {beta}-cell proliferation, while also enhancing GSIS and providing protection against {beta}-cell cytotoxicity through induction of the VGF prohormone. We developed an Nkx6.1 pathway screen by stably transfecting 832/13 rat insulinoma cells with a VGF promoter-luciferase reporter construct, using the resultant cell line to screen a 630,000 compound chemical library. We isolated three compounds with consistent effects to stimulate human islet cell proliferation. Further studies of the most potent of these compounds, GNF-9228, revealed that it selectively activates human {beta}-cell relative to -cell proliferation and has no effect on {delta}-cell replication. In addition, pre-treatment, but not short term exposure of human islets to GNF-9228 enhances GSIS. GNF-9228 also protects 832/13 insulinoma cells against ER stress- and inflammatory cytokine-induced cytotoxicity. In contrast to recently emergent Dyrk1a inhibitors that stimulate human islet cell proliferation, GNF-9228 does not activate NFAT translocation. These studies have led to identification of a small molecule with pleiotropic positive effects on islet biology, including stimulation of human {beta}-cell proliferation and insulin secretion, and protection against multiple agents of cytotoxic stress.

cell biology↗

bioRxiv2019

Small molecule activation of metabolic enzyme pyruvate kinase muscle isozyme 2, PKM2, provides photoreceptor neuroprotection

Photoreceptor cell death is the ultimate cause of vision loss in many retinal disorders, and there is an unmet need for neuroprotective modalities to improve photoreceptor survival. Similar to cancer cells, photoreceptors maintain pyruvate kinase muscle isoform 2 (PKM2) expression, which is a critical regulator in aerobic glycolysis. Unlike PKM1, which has constitutively high catalytic activity, PKM2 is under complex regulation. Recently, we demonstrated that genetically reprogramming photoreceptor metabolism via PKM2-to-PKM1 substitution is a promising neuroprotective strategy. Here, we explored the neuroprotective effects of pharmacologically activating PKM2 via ML-265, a small molecule activator of PKM2, during acute outer retinal stress. We found that ML-265 increased PKM2 activity in 661W cells and in vivo in rat eyes without affecting the expression of genes involved in glucose metabolism. ML-265 treatment did, however, alter metabolic intermediates of glucose metabolism and those necessary for biosynthesis in cultured cells. Long-term exposure to ML-265 did not result in decreased photoreceptor function or survival under baseline conditions. Notably, though, ML-265-treatment did reduce entrance into the apoptotic cascade in in vitro and in vivo models of outer retinal stress. These data suggest that reprogramming metabolism via activation of PKM2 is a novel, and promising, therapeutic strategy for photoreceptor neuroprotection.

molecular biology↗

bioRxiv2019

Field decomposition of Bt-506 corn leaf and its effect on Collembola in the black soil region of China

The litters of Bt corn would go into the soil through straw returning and field ploughing after cultivation. To clarify whether the leaf litter decomposition rate and the non-target soil Collembola were influenced by the Bt protein or other litter properties in leaf litters of Bt corn in Northeast China, leaf litterbags of Bt-506, its near isoline Zheng 58 and a local type Zhengdan 958 were used in the field in Northeast China. The leaf decomposition rate, the leaf properties and the collembolan community in litterbags were investigated later. After seven months, only 43.5 ng/g Bt protein in Bt-506 leaf litter was left. All the investigated indices were not significantly different between Bt-506 and its near isoline Zheng 58. But when compared with local type Zhengdan 958, Bt-506 and its near isoline Zheng 58 contained lower non-structural carbohydrate content but higher total nitrogen content, and had lower litter decomposition rate and less abundance of Collembola. Collembolan abundance and litter decomposition rate were both significantly correlated with the non-structural carbohydrate and total nitrogen contents of the leaf litters. Field study results revealed Bt protein did not affect the leaf litter decomposition rate and the collembolan community in leaf litterbags in short term. The significant differences of these investigated indices among corn types were caused by the different non-structural carbohydrate and total nitrogen contents in leaf litter.

ecology↗

bioRxiv2019

DeepMicro: deep representation learning for disease prediction based on microbiome data

Human microbiota plays a key role in human health and growing evidence supports the potential use of microbiome as a predictor of various diseases. However, the high-dimensionality of microbiome data, often in the order of hundreds of thousands, yet low sample sizes, poses great challenge for machine learning-based prediction algorithms. This imbalance induces the data to be highly sparse, preventing from learning a better prediction model. Also, there has been little work on deep learning applications to microbiome data with a rigorous evaluation scheme. To address these challenges, we propose DeepMicro, a deep representation learning framework allowing for an effective representation of microbiome profiles. DeepMicro successfully transforms high-dimensional microbiome data into a robust low-dimensional representation using various autoencoders and applies machine learning classification algorithms on the learned representation. In disease prediction, DeepMicro outperforms the current best approaches based on the strain-level marker profile in five different datasets. In addition, by significantly reducing the dimensionality of the marker profile, DeepMicro accelerates the model training and hyperparameter optimization procedure with 8X-30X speedup over the basic approach. DeepMicro is freely available at https://github.com/minoh0201/DeepMicro.

bioinformatics↗

bioRxiv2019

A functional cortical network for sensorimotor sequence generation

The brain generates complex sequences of movements that can be flexibly reconfigured in real-time based on sensory feedback, but how this occurs is not fully understood. We developed a novel sequence licking task in which mice directed their tongue to a target that moved through a series of locations. Mice could rapidly reconfigure the sequence online based on tactile feedback. Closed-loop optogenetics and electrophysiology revealed that tongue/jaw regions of somatosensory (S1TJ) and motor (M1TJ) cortex encoded and controlled tongue kinematics at the level of individual licks. Tongue premotor (anterolateral motor, ALM) cortex encoded intended tongue angle in a smooth manner that spanned individual licks and even whole sequences, and progress toward the reward that marked successful sequence execution. ALM activity regulated sequence initiation, but multiple cortical areas collectively controlled termination of licking. Our results define a functional cortical network for hierarchical control of sensory- and reward-guided orofacial sequence generation.

neuroscience↗

bioRxiv2019

Satellite Imaging of Global Urbanicity relate to Adolescent Brain Development and Behavior

Urbanicity, the impact of living in urban areas, is among the greatest environmental challenges for mental health. While urbanicity might be distinct in different sociocultural conditions and geographic locations, there are likely to exist common features shared in different areas of the globe. Understanding these common and specific relations of urbanicity with human brain and behavior will enable to assess the impact of urbanicity on mental disorders, especially in childhood and adolescence, where prevention and early interventions are likely to be most effective.\n\nWe constructed from satellite-based remote sensing data a factor for urbanicity that was highly correlated with population density ground data. This factor, UrbanSat was utilized in the Chinese CHIMGEN sample (N=831) and the longitudinal European IMAGEN cohort (N=810) to investigate if exposure to urbanicity during childhood and adolescence is associated with differences in brain structure and function in young adults, and if these changes are linked to behavior.\n\nUrbanicity was found negatively correlated with medial prefrontal cortex volume and positively correlated with cerebellar vermis volume in young adults from both China and Europe. We found an increased correlation of urbanicity with functional network connectivity within- and between- brain networks in Chinese compared to European participants. Urbanicity was highly correlated with a measure of perceiving a situation from the perspective of others, as well as symptoms of depression in both datasets. These correlations were mediated by the structural and functional brain changes observed. Susceptibility to urbanicity was greatest in two developmental windows during mid-childhood and adolescence.\n\nUsing innovative technology, we were able to probe the relationship between urban upbringing with brain change and behavior in different sociocultural conditions and geographic locations. Our findings help to identify shared and distinct determinants of adolescent brain development and mental health in different regions of the world, thus contributing to targeted prevention and early-intervention programs for young people in their unique environment. Our approach may be relevant for public health, policy and urban planning globally.

neuroscience↗

bioRxiv2019

Wheat Germ Agglutinin Conjugated Fluorescent pH Sensors for Visualizing Proton Fluxes

Small molecule fluorescent wheat germ agglutinin (WGA) conjugates are routinely used to demarcate mammalian plasma membranes because they bind to the cells glycocalyx. Here we describe the derivatization of WGA with a pH sensitive rhodamine fluorophore (pHRho: pKa = 7) to detect proton channel fluxes and extracellular proton accumulation and depletion from primary cells. We found that WGA-pHRho labeling was uniform, did not appreciably alter the voltage-gating of glycosylated ion channels, and the extracellular changes in pH directly correlated with proton channel activity. Using single plane illumination techniques, WGA-pHRho was used to detect spatiotemporal differences in proton accumulation and depletion over the extracellular surface of cardiomyocytes, astrocytes, and neurons. Because WGA can be derivatized with any small molecule fluorescent ion sensor, WGA conjugates should prove useful to visualize most electrogenic and non-electrogenic events on the extracellular side of the plasma membrane.

biophysics↗

bioRxiv2019

CpG-ODN 2007 protects zebrafish against Vibrio vulnificus-induced infection

Vibrio vulnificus (V. vulnificus) is an aquatic pathogen that can cause primary sepsis and soft tissue infection. CpG oligodeoxynucleotides (CpG-ODN) are a type of essential immunomodulators, which can trigger or enhance immune responses in mammals, fish, and humans. In this study, we evaluated the effect of CpG-ODN 2007 as a potential immunostimulant for zebrafish infected with V. vulnificus (FJ03-X2). Fish injected with the CpG-ODN 2007 showed lower mortality rate compared with the fish that did not receive treatment. The survival rates of CpG-ODN 2007-treated group and PBS-treated group were 85% and 57.9%, respectively. In addition, our in vitro results demonstrated that CpG-ODN 2007 can effectively reduce the toxicity of V. vulnificus (FJ03-X2) to zebrafish embryonic fibroblast (ZF4) cells. Furthermore, we assessed immune-related genes expression patterns in FJ03-X2 infected zebrafish or ZF4 cells with and without CpG-ODN 2007 treatment, such as TLRs and IL-1{beta}. To sum up, our data indicated that CpG-ODN 2007 protects zebrafish against Vibrio vulnificus induced infection.

immunology↗

bioRxiv2019

Fertility of Pedicellate Spikelets in Sorghum is Controlled by a Jasmonic Acid Regulatory Module

As in other cereal crops, the panicles of sorghum (Sorghum bicolor (L.) Moench) comprise two types of floral spikelets (grass flowers). Only sessile spikelets (SSs) are capable of producing viable grains, whereas pedicellate spikelets (PSs) cease development after initiation and eventually abort. Consequently, grain number per panicle (GNP) is lower than the total number of flowers produced per panicle. The mechanism underlying this differential fertility is not well understood. To investigate this issue, we isolated a series of EMS-induced multiseeded (msd) mutants that result in full spikelet fertility, effectively doubling GNP. Previously, we showed that MSD1 is a TCP (Teosinte branched/Cycloidea/PCF) transcription factor that regulates jasmonic acid (JA) biosynthesis, and ultimately floral sex organ development. Here, we show that MSD2 encodes a lipoxygenase (LOX) that catalyzes the first committed step of JA biosynthesis. Further, we demonstrate that MSD1 binds to the promoters of MSD2 and other JA pathway genes. Together, these results show that a JA-induced module regulates sorghum panicle development and spikelet fertility. The findings advance our understanding of inflorescence development and could lead to new strategies for increasing GNP and grain yield in sorghum and other cereal crops.\n\nSignificanceThrough a single base pair mutation, grain number can be increased by ~200% in the globally important crop Sorghum bicolor. This mutation affects the expression of an enzyme, MSD2, that catalyzes the jasmonic acid pathway in developing floral meristems. The global gene expression profile in this enzymatic mutant is similar to that of a transcription factor mutant, msd1, indicating that disturbing any component of this regulatory module disrupts a positive feedback loop that occurs normally due to regular developmental perception of jasmonic acid. Additionally, the MSD1 transcription factor is able to regulate MSD2 in addition to other jasmonic acid pathway genes, suggesting that it is a primary transcriptional regulator of this hormone signaling pathway in floral meristems.

plant biology↗

bioRxiv2019

Lesions of canine prostate underwent laser ablation, radiofrequency ablation, and microwave ablation: Lesions shapes and clinical significances

ObjectiveTo explore the shapes and clinical significances of the lesions of canine prostate underwent laser ablation (LA), radiofrequency ablation (RFA), and microwave ablation (MWA).\n\nMethodsHere, 6 male Beagle dogs were randomly assigned to LA, RFA, and MWA groups, respectively. The ablations were conducted with the doses commonly applied in clinical practice (LA: 3 W/1200 J; RFA and MWA: 30 W/120 s) for one region in the left and right lobes of the prostate, which totally resulted in 12 lesions. An energy transmitter was inserted via the perineum under the guidance of transrectal ultrasound (TRUS) and the ablation process was observed dynamically. After ablation, the efficacy was assessed by contrast-enhanced ultrasonography (CEUS), and transverse diameter (TRD), anteroposterior diameter (APD), and longitudinal diameter (TRD) were measured. Then, the volume (V) was calculated according to the following formulae, V = 1/6 x {pi} x (MLD x APD x LD), and ratio (R) R =[(MLD + APD)/2 x LD], which was used to show the shape of the lesion (The closer R is to 1, the more spherical it is).\n\nResultsThe shapes and sizes of the lesions underwent the three techniques varied under the clinically commonly used doses. The R values, reflecting the changes in shapes of lesions, were 0.89{+/-}0.02, 0.72{+/-}0.01, and 0.65{+/-}0.03 for RFA, MWA, and LA, respectively, which were significantly different (P =0.027). The volumes of the lesions underwent the three ablation techniques significantly varied as well (P=0.001), which were 2.17{+/-}0.10, 1.51{+/-}0.20, and 0.79{+/-}0.07 ml for MWA, LA, and RFA, respectively. Conclusion: The above-mentioned three techniques could be used for ablation of prostate cancer using the clinically commonly used doses. The shapes of the lesions underwent the three ablation techniques varied evidently, with the lesions received RFA and LA were more spherical and oval, respectively, while the shapes of lesions underwent MWA were between spherical and oval. The lesions received MWA and RFA had the largest and smallest sizes, respectively, while sizes of lesions underwent LA were in the middle. These findings may assist physicians to select an appropriate therapeutic method for treatment of prostate disease.

cancer biology↗

bioRxiv2019

Why does a flying fish taxi on sea surface before take-off? A hydrodynamic interpretation

Flying fish have been observed jumping out of warm ocean waters worldwide. Before take-off, the flying fish are seen to taxi on the water surface by rapidly beating their semi-submerged tail fins, which process may help them airborne with enough speed to glide over a long distance. To understand the underlying physical mechanisms, here, we study a flying fish, 0.25 m in length and 0.191 kg in weight, considering both its underwater swimming and surface taxiing locomotion. Its hydrodynamic characteristics are numerically studied by computational fluid dynamics (CFD). Underwater, the fish is assumed to swim at a constant speed of 10 m s-1. Different critical frequencies are identified for various maximum deflected angles, ranging from{theta} 0 = 10{degrees} to 30{degrees}, at which the fish reaches cruising states, when the horizontal forces are balanced. The corresponding minimum power required for cruising swimming is 350 W, obtained at a deflected angle of 10{degrees} and a critical frequency of 145 Hz. In contrast, in the taxiing stage, the minimum power required for a stead-state locomotion at 10 m s-1 is 36 W, occurring at a deflected angle of 15{degrees} and a frequency of 50 Hz. We note that the power is significantly smaller than the swimming locomotion. Further, by increasing the flapping power, we find that larger speeds can be achieved. In specific, when the power is brought up to 350 W, it can reach a speed of 16.5 m s-1. Clearly, from the direct comparison between the two locomotive modes, it is apparently evidenced that the flying fish can be further accelerated by taxiing along the water surface.

zoology↗

bioRxiv2019

Integrated Proteogenomic Deep Sequencing and Analytics Accurately Identify Non-Canonical Peptides in Tumor Immunopeptidomes

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides that derive from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides and of an immunogenic peptide from a downstream reading frame in the melanoma stem cell marker gene ABCB5. It holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

cancer biology↗

bioRxiv2019

Streptococcus pyogenes Cas9 displays biased one-dimensional diffusion on dsDNA to search for a target

The RNA-guided Streptococcus pyogenes Cas9 (spCas9) is a sequence-specific DNA endonuclease that works as one of the most powerful genetic editing tools. However, how the Cas9 locates its target among huge amounts of dsDNAs remains controversial. Here, combining biochemical and single-molecule assays, we revealed that Cas9 uses both three-dimensional and one-dimensional diffusion to find its target. We further observed a surprising biased one-dimensional diffusion of Cas9 from 3 to 5 end of the non-target strand under physiological salt condition, whereas low ionic concentration or mutations on PAM recognition residues induce unbiased one-dimensional diffusion of Cas9 along dsDNA. We quantified the diffusion length of 27 bp, which accelerates the target search efficiency of Cas9 by [~] 10 folds. Our results reveal a unique searching mechanism of Cas9 at physiological salt conditions, and provide important guidance for both in-vitro and in-vivo applications of Cas9.

biochemistry↗

bioRxiv2019

TRIM21 and PHLDA3 Negatively Regulate the Cross-Talk between the PI3K/AKT Pathway and PPP Metabolism

PI3K/AKT signaling is known to regulate cancer metabolism but whether metabolic pathway feedbacks and regulates the PI3K/AKT pathway is unclear. Here, we demonstrate the important reciprocal cross-talks between the PI3K/AKT signal and PPP branching metabolic pathways. PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of PPP, by inhibiting a newly identified E3 ligase TIRM21, and promotes PPP. PPP metabolites, in turn, reinforce AKT activation and further promote cancer metabolic reprogramming by blocking the expression of an AKT inhibitor PHLDA3. Knockout TRIM21 or PHLDA3 promotes the cross-talks and cell proliferation. Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of these reciprocal cross-talks may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.

cancer biology↗

bioRxiv2019

Sag currents are a major contributor to human pyramidal cell intrinsic differences across cortical layers and between individuals

In the human neocortex coherent interlaminar theta oscillations are driven by deep cortical layers, suggesting neurons in these layers exhibit distinct electrophysiological properties. To characterize this potential distinctiveness, we use in vitro whole-cell recordings from cortical layers 2 and 3 (L2&3), layer 3c (L3c) and layer 5 (L5) of the human cortex. Across all layers we observe notable heterogeneity, indicating human cortical pyramidal neurons are an electrophysiologically diverse population. L5 pyramidal cells are the most excitable of these neurons and exhibit the most prominent sag current (abolished by blockade of the hyperpolarization activated cation current, Ih). While subthreshold resonance is more common in L3c and L5, we rarely observe this resonance at frequencies greater than 2Hz. However, the frequency dependent gain of L5 neurons reveals they are most adept at tracking both delta and theta frequency inputs, a unique feature that may indirectly be important for the generation of cortical theta oscillations.

neuroscience↗

bioRxiv2019

Close homologue of L1 sensitizes lung cancer cells to cisplatin and paclitaxel via inhibition Akt pathway

Drug resistance is a serious promble during chemotherapy in lung cancer, which may lead to tumor relapse and further progression. CHL1 was a tumor suppressor in most malignancies, and it was found downregulated in NSCLC cisplatin-resistant cells H460. Thus, in this study, we investigated the role and mechanism of chemoresistance by CHL1 in lung cancer. Human lung adenocarcinoma cell lines A549 and its cisplatin resistant cells (A549/DDP) and paclitaxel resistant cells (A549/PTX) were applied in this research. CHL1 was found obvious downregulation in A549/DDP and A549/PTX cells versus A549 cells. Suppression of CHL1 in A549 cells, promoted cell survival rate and clone formation, decreased cell apoptosis when treated with or without DDP and PTX, respectively. While excessive CHL1 expression in A549/DDP and A549/PTX cells, the results were opposite. Moreover, CHL1 knockdown mediating chemoresistance was reversed by Akt inhibitor SC66 in A549 cells. In summary, overexpression of CHL1 reversed chemoresistance to cisplatin and PTX via suppressing Akt pathway in lung cancer, it was suggested that CHL1 maybe as a potential target for overcome chemoresistance in lung cancer.

cancer biology↗

bioRxiv2019

Generating Templates and Growth Charts for School-Aged Brain Development

Standard brain templates and growth charts provide an invaluable resource for basic science research, with the eventual goal of contributing to the clinical care of neuropsychiatric conditions. Here, we report on a protocol to generate MRI brain templates in children and adolescents at one-year intervals from 6-to-18 years of age, with their corresponding growth charts, using a large-scale neuroimaging data resource (948 brain images from China and United States). To assure that the brain templates and growth charts are reliable and accurate, we developed a refined pipeline consisting of template construction, image registration, brain area labeling and growth chart modeling. The pipeline comprises multiple modular workflows that can be used for multiple applications. In our approach, population- and age-specific templates were first constructed to avoid systemic bias in registration. Brain areas were then labeled based on the appropriate templates, and their morphological metrics were extracted for modeling associated growth curves. We implemented warp cost as a function of age differences between individual brains and template brains. A strong U-shaped cost function was revealed, indicating larger age differences are associated with greater registration errors. This validates the necessity of age-specific reference templates in pediatric brain imaging studies. Growth chart analyses revealed preferential shape differences between Chinese and US samples in lateral frontal and parietal areas, aspects of cortex which are most variable across individuals with regard to structure and function as well as associated behavioral performance. This growth distinction is largely driven by neurodevelopmental differences between Chinese and US age-specific brain templates. The pipeline together with the brain templates and charts are publicly available and integrated into the Connectome Computation System.

neuroscience↗