Biology subjects

Hu, H.

Publications and source records attributed to Hu, H..

At least 217 records · Page 12Linked to original sources

bioRxiv2021

The creation of functioning gastrojejunostomy following magnetic compression

BackgroundMagnetic compression for creating gastrojejunostomy has many advantages according to previous studies. However, following mechanical device release after healing, the anastomotic stenosis becomes the pivotal point. MethodsRectangle-shaped magnets were used for magnetic compression in rabbits. Both paclitaxel-loaded magnets and a strategy of pyloric ligation were chosen to improve the gastrojejunostomy. Based on these choices, the half-capsule was applied to occlude the pylorus after anastomotic formation. The size and patency of the anastomoses were analyzed to evaluate the efficacy of these approaches. A histological examination was also performed. ResultsThe positive effect of ligating the pylorus on gastrojejunostomy was significantly greater than that achieved using paclitaxel-loaded magnets during either short- or long-term follow-up. There were fewer scar tissue and collagen fibers at the anastomotic site in the treatment group than in the control group. The anastomotic aperture was of great interest at 9 months after the ligation of the pylorus following magnetic compression. In the view of the jejunum, although the aperture was barely visible, gastric juice was continuously spilling through it like a spring, and the aperture was clearly visible from the stomach side. All half-capsules failed to block the pylorus. ConclusionThe effect of paclitaxel on maintaining gastrojejunostomy patency was temporary. The ligation of the pylorus ensured the long-term patency of gastrojejunostomy, and the aperture was comparable to the pylorus which could play an anti-reflux role. Further studies for the sort of gastrointestinal aperture are being planned.

physiology↗

bioRxiv2021

Bmmp influences wing shape by regulating anterior-posterior and proximal-distal axis development

Insect wings are subject to strong selective pressure, resulting in the evolution of remarkably diverse wing shapes that largely determine flight capacity. However, the genetic basis and regulatory mechanisms underlying wing shape development are not well understood. The silkworm Bombyx mori micropterous (mp) mutant exhibits shortened wing length and enlarged vein spacings, albeit without changes in total wing area. Thus, the mp mutant comprises a valuable genetic resource for studying wing shape development. In this study, we used molecular mapping to identify the gene responsible for the mp phenotype and designated it Bmmp. Phenotype-causing mutations were identified as indels and single nucleotide polymorphisms in non-coding regions. These mutations resulted in decreased Bmmp mRNA levels and changes in transcript isoform composition. Bmmp null mutants were generated by CRISPR/Cas9 and exhibited significantly smaller wings. By examining the expression of genes critical to wing development in wildtype and Bmmp null mutants, we found that Bmmp exerts its function by coordinately modulating anterior-posterior and proximal-distal axis development. We also studied a Drosophila mp mutant and found that Bmmp is functionally conserved in Drosophila. The Drosophila mp mutant strain exhibits curly wings of reduced size and a complete loss of flight capacity. Our results increase our understanding of the mechanisms underpinning insect wing development and reveal potential targets for pest control.

genetics↗

bioRxiv2021

Typical and disrupted brain circuitry for conscious awareness in full-term and preterm infants

One of the great frontiers of consciousness science is understanding how early consciousness arises in the development of the human infant. The reciprocal relationship between the default mode network (DMN) and frontoparietal networks -- the dorsal attention network (DAN) and executive control network (ECN) -- is thought to facilitate integration of information across the brain and its availability for conscious access to a wide set of mental operations. It remains unknown whether the brain mechanism of conscious awareness is instated in infants from birth. To address this gap, we asked what the impact of prematurity and neonate age is on the development the default mode and fronto-parietal networks, and of their reciprocal relationship. To address these questions, we used the Developing Human Connectome Project (dHCP), a unique Open Science project which provides a large sample of neonatal functional Magnetic Resonance Imaging (fMRI) data with high temporal and spatial resolution. Resting state fMRI data for full-term neonates (N = 282, age 41.2 w {+/-} 12 d), and preterm neonates scanned at term-equivalent age (TEA) (N = 73, 40.9 w {+/-} 14.5 d), or before TEA (N = 73, 34.6 w {+/-} 13.4 d) were obtained from the dHCP, and for a reference adult group (N = 176, 22 - 36 years), from the Human Connectome Project. For the first time, we show that the reciprocal relationship between the DMN and DAN was present at full-term birth or TEA. Although different from the adult networks, the DMN, DAN and ECN were present as distinct networks at full-term birth or TEA, but premature birth disrupted network development. By contrast, neonates before TEA showed dramatic underdevelopment of high-order networks. Only the DAN was present as a distinct network and the reciprocal network relationship was not yet formed. Our results suggest that, at full-term birth or by term-equivalent age, infants possess key features of the neural circuitry that enables integration of information across diverse sensory and high-order functional modules, giving rise to conscious access. Conversely, they suggest that this brain infrastructure is not present before infants reach term-equivalent age. These findings improve understanding of the ontogeny of high-order network dynamics that support conscious awareness, and of their disruption by premature birth.

neuroscience↗

bioRxiv2021

Engineered Bacteriophage T4 Nanoparticle as a Potential Targeted Activator of HIV-1 Latency in CD4+ Human T cells

A major barrier for HIV-1 eradication is the latent virus reservoir containing stably integrated and silent proviruses in CD4+ T-cells. Targeted reactivation and removal of this latent reservoir is a potential strategy for HIV-1 cure but remains a major challenge. Here, we investigated whether CD4-targeted bacteriophage T4 capsid nanoparticles that mimic HIV envelope can reactivate HIV-1 latency. The nanoparticles were arrayed with CD4-binding CD4-DARPin, or HIV-1 gp140 envelope trimer. When exposed to J-Lat T-cell model of HIV-1 latency or primary T-lymphocytes from human PBMCs, these nanoparticles activated CD4+ T-cells without causing global T-cell activation, which led to activation of HIV-1 proviral transcription, viral protein production and release. Intriguingly, the observed T-cell activation and HIV-1 latency reversal do not involve the classic PKC or NFAT pathways and did not lead to cytokine storm. These studies indicate that engineered non-infectious bacteriophages can be exploited for HIV-1 cure and targeted T-cell therapies.

immunology↗

bioRxiv2021

Parvalbumin interneuron dendrites enhance gamma oscillations

Dendrites are important determinants of the input-output relationship of single neurons, but their role in network computations is not well understood. Here, we used a combination of dendritic patch-clamp recordings and in silico modeling to determine how dendrites of parvalbumin (PV)-expressing basket cells contribute to network oscillations in the gamma frequency band. Simultaneous soma-dendrite recordings from PV basket cells in the dentate gyrus revealed that the slope, or gain, of the dendritic input-output relationship is exceptionally low, thereby reducing the cells sensitivity to changes in its input. By simulating gamma oscillations in detailed network models, we demonstrate that the low gain is key to increase spike synchrony in PV neuron assemblies when cells are driven by spatially and temporally heterogeneous synaptic input. These results highlight the role of dendritic computations in synchronized network oscillations.

neuroscience↗

bioRxiv2021

Effect of straw incorporation and nitrification inhibitor on nitrous oxide emission in various cropland soils and its microbial mechanism

Nitrification inhibitor and straw incorporation are widely used to improve crop nitrogen use efficiency in agricultural soil, but their effects on nitrous oxide (N2O) emission across different soil types and the microbial mechanisms remain less understood. In this study, we used controlled experiment and DNA-based molecular analysis to study how nitrification inhibitor (dicyandiamide, DCD) and straw incorporation affect soil nitrogen balance, N2O emission and microbial nitrifiers/denitrifers in three distinct agricultural soils (the black, fluvo-aquic and red soils) across China. Both DCD and straw incorporation improved nitrogen balance by increasing NH4+ and decreasing NO3- in all soils. DCD tended to decrease N2O emission from all soils especially the fluvo-aquic one, while straw incorporation reduced N2O emission only in the fluvo-aquic soil but increased N2O emission in the other two especially the red soil (by [~]600%). T-RFLP analysis revealed that the denitriers community structure are distinct among the three soils but was not strongly affected by DCD or straw incorporation. qPCR analysis revealed that DCD or straw incorporation had no significant effect on nitrifier abundance but increased nitrous oxide reductase nosZ gene abundance in the black/fluvo-aquic soil rather than the red soil. Structural equational modelling further confirmed that, when accounting for treatments and soil properties, nosZ gene abundance is the only biological factor significantly determined N2O emission in different soil types. Taken together, our work advanced the knowledge on the agricultural practices and N2O emission in cropland soils, suggesting that straw incorporation may not be a good choice for the red and black soil areas; management practices should be used as per soil type to balance between nitrogen use efficiency and N2O emission.

ecology↗

bioRxiv2021

Transcriptome analysis reveals higher levels of mobile element-associated abnormal gene transcripts in temporal lobe epilepsy patients

ObjectiveTo determine role of abnormal splice variants associated with mobile elements in epilepsy. MethodsPublicly available human RNA-seq-based transcriptome data for laser-captured dentate granule cells of post-mortem hippocampal tissues from temporal lobe epilepsy patients with (TLE, N=14 for 7 subjects) and without hippocampal sclerosis (TLE-HS, N=8 for 5 subjects) and healthy individuals (N=51), surgically resected bulk neocortex tissues from TLE patients (TLE-NC, N=17). For each individual sample, de novo transcriptome assembly was performed followed by identification of spliced gene transcripts containing mobile element (ME) sequences (ME-transcripts) to compare the ME-transcript frequency across the sample groups. Enrichment analysis for genes associated with ME-transcripts and detailed sequence examination for representative epileptic genes were performed to analyze the pattern and mechanism of ME-transcripts on gene function. ResultsWe observed significantly higher levels of ME-transcripts in the hippocampal tissues of epileptic patients, particularly in TLE-HS. Among ME classes, SINEs were shown to be the most frequent contributor to ME-transcripts followed by LINEs and DNA transposons. These ME sequences almost in all cases represent older MEs normally located in the intron sequences, leading abnormal splicing variants. For protein coding genes, ME sequences were mostly found in the 3-UTR regions, with a significant portion also in the coding sequences (CDS) leading to reading frame disruption. Genes associated with ME-transcripts showed enrichment for involvement in the mRNA splicing process in all sample groups, with bias towards neural and epilepsy-associated genes in the epileptic transcriptomes. SignificanceOur data suggest that abnormal splicing involving MEs, leading to loss of function in critical genes, plays a role in epilepsy, particularly in TLE-HS, providing a novel insight on the molecular mechanisms underlying epileptogenesis. Key points boxO_LISignificantly higher rates of abnormal splicing variants involving mobile elements (MEs) were observed in the hippocampal tissues of epilepsy patients. C_LIO_LISINEs/Alus are most frequently observed in ME-transcripts followed by LINEs and DNA transposons. C_LIO_LIFor protein coding genes, MEs mostly locate in 3 UTR, but also in coding regions, causing open reading frame disruption, with a bias for neural and epileptic genes. C_LIO_LIAbnormal splicing involving MEs may be a contributing factor in epileptogenesis. C_LI

neuroscience↗

bioRxiv2021

Multi-omics prediction of oat agronomic and seed nutritional traits across environments and in distantly related populations

Multi-omics prediction has been shown to be superior to genomic prediction with genome-wide DNA-based genetic markers (G) for predicting phenotypes. However, most of the existing studies were based on historical datasets from one environment; therefore, they were unable to evaluate the efficiency of multi-omics prediction in multi-environment trials and distantly-related populations. To fill those gaps, we designed a systematic experiment to collect omics data and evaluate 17 traits in two oat breeding populations planted in single and multiple environments. In the single-environment trial, transcriptomic BLUP (T), metabolomic BLUP (M), G+T, G+M and G+T+M models showed greater prediction accuracy than GBLUP for 5, 10, 11, 17 and 17 traits, respectively, and metabolites generally performed better than transcripts when combined with SNPs. In the multi-environment trial, multi-trait models with omics data outperformed both counterpart multi-trait GBLUP models and single-environment omics models, and the highest prediction accuracy was achieved when modeling genetic covariance as an unstructured covariance model. We also demonstrated that omics data can be used to prioritize loci from one population with omics data to improve genomic prediction in a distantly-related population using a two-kernel linear model that accommodated both likely casual loci with large-effect and loci that explain little or no phenotypic variance. We propose that the two-kernel linear model is superior to most genomic prediction models that assume each variant is equally likely to affect the trait and can be used to improve prediction accuracy for any trait with prior knowledge of genetic architecture.

genetics↗

bioRxiv2021

Expanding Asgard members in the domain of Archaea shed new light on the origin of eukaryotes

The hypothesis that eukaryotes originated from within the domain Archaea has been strongly supported by recent phylogenomic analyses placing Heimdallarchaeota from the Asgard superphylum as the closest known archaeal sister-group to eukaryotes. At present, only six phyla are described in the Asgard superphylum, which limits our understanding of the relationship between eukaryotes and archaea, as well as the evolution and ecological functions of the Asgard archaea. Here, we describe five previously unknown phylum-level Asgard archaeal lineages, tentatively named Tyr-, Sigyn-, Freyr-, Njord- and Balderarchaeota. Comprehensive phylogenomic analyses further supported the origin of eukaryotes within Archaea and a new Asgard lineage Njordarchaeota was supposed as the known closest branch with the eukaryotic nuclear host lineage. Metabolic reconstruction suggests that the Asgard archaea described here have potential to fix inorganic carbon via the Wood-Ljungdahl pathway and degrade organic matters except Njordarchaeota, which may possess a heterotrophic lifestyle with capability of peptides and amino acids utilization. Additionally, the Ack/Pta pathway for homoacetogenesis and de novo anaerobic cobalamin biosynthesis pathway were found in Balderarchaeota and Tyrarchaeota, respectively. This study largely expands the Asgard superphylum, provides additional evidences to support the 2-domain life tree and sheds new light on the evolution of eukaryotes.

evolutionary biology↗

bioRxiv2021

Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo.

Retinoic acid receptor-related orphan nuclear receptor (ROR) {gamma}t is a member of the RORC nuclear hormone receptor family of transcription factors. ROR{gamma}t functions as a critical regulator of thymopoiesis and immune responses. ROR{gamma}t is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the ROR{gamma}t/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric ROR{gamma}t inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, ROR{gamma}t inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids.

immunology↗

bioRxiv2021

Expanded Asgard archaea shed new light on the origin of eukaryotes and support a 2-domain tree of life

The hypothesis that eukaryotes originated from within the domain Archaea has been strongly supported by recent phylogenomic analyses placing Heimdallarchaeota from the Asgard superphylum as the closest known archaeal sister-group to eukaryotes. At present, only seven phyla are described in the Asgard superphylum, which limits our understanding of the relationship between eukaryotes and archaea, as well as the evolution and ecological functions of Asgard archaea. Here, we describe five novel phylum-level Asgard archaeal lineages, tentatively named Tyr-, Sigyn-, Freyr-, Hoder- and Balderarchaeota. Comprehensive phylogenomic analyses supported a new Asgard lineage Tyrarchaeota was identified as a deeper branching lineage cluster with the eukaryotic nuclear host lineage than Heimdallarchaeota that were previously considered as the closest archaeal relatives of eukaryotes. Metabolic reconstruction of Tyrarchaeota suggests a mixotrophic lifestyle of this archaea, capable of peptides and amino acids utilization while having the potential using the Wood-Ljungdahl pathway for carbon fixation and acetogenesis. This study largely expands the Asgard superphylum, provides additional evidences to support the 2-domain life tree thus sheds new light on the evolution and geochemical functions of the Asgard archaea.

evolutionary biology↗

bioRxiv2021

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2-) macrophages. Herein, we identify an essential role for CCR2- macrophages in the chronically failing heart. Depletion of CCR2- macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2- macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.

immunology↗

bioRxiv2021

Neuromodulation of Behavioral Specialization: Tachykinin Signaling Inhibits Task-Specific Behavioral Responsiveness in Honeybee Workers

Behavioral specialization is key to the success of social insects and often compartmentalized among colony members leading to division of labor. Response thresholds to task-specific stimuli proximally regulate behavioral specialization but their neurobiological regulation is not understood. Here, we show that response thresholds to task-relevant stimuli correspond to the specialization of three behavioral phenotypes of honeybee workers. Quantitative neuropeptidome comparisons suggest two tachykinin-related peptides (TRP2 and TRP3) as candidates for the modification of these response thresholds. Based on our characterization of their receptor binding and downstream signaling, we then confirm the functional role of tachykinins: TRP2 injection and RNAi cause consistent, opposite effects on responsiveness to task-specific stimuli of each behaviorally specialized phenotype but not to stimuli that are unrelated to their tasks. Thus, our study demonstrates that TRP-signaling regulates the degree of task-specific responsiveness of specialized honeybee workers and may control the context-specificity of behavior in animals more generally.

evolutionary biology↗

bioRxiv2020

Hundreds of motif pairs may facilitate enhancer-promoter interactions

Previous studies have shown that pairs of interacting transcription factors (TFs) bind to enhancers and promoters and contribute to their physical interactions. However, to date, we have limited knowledge about these interacting TF pairs. To identify such TF pairs, we systematically studied the co-occurrence of TF-binding motifs in interacting enhancer-promoter (EP) pairs in seven human cell lines. We discovered hundreds of motif pairs that significantly co-occur in enhancers and promoters of interacting EP pairs. We demonstrated that these motif pairs are biologically meaningful and significantly enriched with motif pairs of known interacting TF pairs. We also showed that the identified motif pairs facilitated the discovery of the interacting EP pairs. The predicted motifs and motif pairs are available at http://www.cs.ucf.edu/~xiaoman/ET/EPmotif/.

genomics↗

bioRxiv2020

Bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure

Exposure to chronic stress induces anxiety-like behavior and metabolic changes in animals, resulting in adaptive or maladaptive responses to the stressful environment. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both anxiety and energy homeostasis. However, up to now, how dmVMH neurons exert dual control of chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we established a chronic-stress mouse model that induced anxiety-like behavior, reduced food consumption, and decreased energy expenditure. We found that c-fos expression increased and theta band power is higher in the dmVMH after chronic stress, and the proportion of burst firing neurons significantly increased, which was mediated by elevated expression of T-type calcium channel Cav 3.1. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects. Collectively, our study first revealed an important role of dmVMH burst firing in the dual regulation of anxiety-like behavior and energy expenditure, and identified Cav 3.1 as a crucial regulator of the activity of the burst firing neurons in dmVMH. These molecular and cellular level findings will advance our understanding of the chronic stress-induced emotional malfunction and energy expenditure disorders.

neuroscience↗

bioRxiv2020

Precise Regulation and Site-specifically Covalent Labeling of NSUN2 Enable by Genetic Encoding Expansion

RNA plays a critical role in gene expression regulation, cell migration, differentiation, cell death in living organism. 5-Methylcytosine is a post transcriptional RNA modification identified across wide ranges of RNA species including message RNAs. It is reported the addition of m5C to RNA cytosines is enabled by use of NSUN family enzyme, NSUN2 is identified as a critical RNA methyltransferase for adding m5C to mRNA. We demonstrated here that natural lysines modified with special groups were synthesized via chemical synthesis. Through two rounds of positive screening and one round of negative screening, MbPylRS-tRNAcua unnatural lysine substitution system which can specifically recognize lysine with defined group was evaluated and identified. Non-natural lysine substitution at C271 of NSUN2 active site and subsequently fluorescent labeling was realized via so-called click reaction. The function of NSUN2 mutant and its upregulated CDK1 gene and its effect on cell proliferation were also evaluated.

molecular biology↗

bioRxiv2020

Peptide Ancestry Informative Markers in Uterine Neoplasms from Women of European, African and Asian Ancestry

Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.

cancer biology↗

bioRxiv2020

Chemoproteomics Maps Glycolytic Targetome in Cancer Cells

Hyperactivated glycolysis, favoring uncontrolled growth and metastasis by producing essential metabolic intermediates engaging bioenergetics and biosynthesis, is a metabolic hallmark of most cancer cells. Although sporadic information has revealed glycolytic metabolites also possess non-metabolic function as signaling molecules, it remains largely elusive how these metabolites interact with and functionally regulate their binding targets. Here we introduce a Target Responsive Accessibility Profiling (TRAP) approach that measures ligand binding-induced steric hindrance in protein targets via global profiling accessibility changes in reactive lysines, and mapped 913 target candidates and 2,487 interactions for 10 major glycolytic metabolites in cancer cells via TRAP. The elucidated targetome uncovers diverse regulatory modalities of glycolytic metabolites involving the direct perturbation of carbohydrate metabolism enzymes, intervention of transcriptional control, modulation of proteome-level acetylation and protein complex assemblies. The advantages gained from glycolysis by cancer cells are expanded by discovering lactate as a ligand for an orphan transcriptional regulator TRIM 28 that promotes p53 degradation, and by identifying pyruvate acting against a cell apoptosis inducer trichostatin A via attenuating protein acetylation. Lastly, the inhibition of glycolytic key enzymes led to identify an intrinsically active glycolytic intermediate glyceraldehyde 3-phosphate that elicits its cytotoxicity by engaging with ENO1 and MTHFD1. Collectively, the glycolytic targetome depicted by TRAP constitutes a fertile resource for understanding how glycolysis finely tunes metabolism and signaling in support of cancer cells, and fostering the exploitation of glycolytic targetome as promising nodes for anti-cancer therapeutics development.

cancer biology↗