Biology subjects

He, T.

Publications and source records attributed to He, T..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

P bodies coat germ granules to promote transgenerational gene silencing in C. elegans

The formation of biomolecular condensates has emerged as a critical mechanism for compartmentation in living cells. Despite interactions between distinct condensates having been reported, the biological relevance of these interactions remains elusive. In germ cells, small RNA silencing factors are enriched in germ granule condensates, where distinct factors are organized into sub-compartments with specific functions linked to genome surveillance or transgenerational gene silencing. Here we showed that perinuclear germ granules are coated by P body condensates, which are known for housing translationally-inactive mRNAs and mRNA degradation factors. Disruption of P body factors, including CGH-1/DDX6 and CAR-1/LSM14, lead to dispersal of small RNA factors from perinuclear germ granules and disorganization of sub-compartments within germ granules. We further found that CAR-1 promotes the interaction between CGH-1 and germ granule factors, and these interactions are critical for the ability of CGH-1 to promote piRNA-mediated gene silencing. Importantly, we observed that cgh-1 mutants are competent in triggering gene silencing but exhibit defects in maintaining gene silencing in subsequent generations. Small RNA sequencing further showed that cgh-1 mutants exhibit defects in amplifying secondary small RNAs, known carriers of gene silencing memories. Together, our results uncover the function of P body factors in small RNA-mediated transgenerational gene silencing and highlight how the formation and function of one condensate can be regulated by an adjacent, interacting condensate in cells.

cell biology↗

bioRxiv2022

A di-arginine additive for dissociation of gold nanoparticle aggregates: A matrix-insensitive approach with applications in protease detection

We report the reversible aggregation of gold nanoparticle (AuNPs) assemblies via a diarginine peptide additive and thiolated PEGs (HS-PEGs). The AuNPs were first aggregated by attractive forces between the citrate-capped surface and the arginine side chains. We found that HS-PEG thiol group has higher affinity for the AuNPs surface, thus leading to redispersion and colloidal stability. In turn, there was a robust and obvious color change due to on/off plasmonic coupling. The assemblies dissociation was directly related to the HS-PEG structural properties such as their size or charge. As an example, HS-PEGs with a molecular weight below 1 kDa could dissociate 100% of the assemblies and restore the exact optical properties of the initial AuNPs suspension (prior to the assembly). Surprisingly, the dissociation capacity of HS-PEGs was not affected by the composition of the operating medium and could be performed in complex matrices such as plasma, saliva, bile, urine, cell lysates or even sea water. The high affinity of thiols for the gold surface encompasses by far the one of endogenous molecules and is thus favorized. Moreover, starting with AuNPs already aggregated ensured the absence of background signal as the dissociation of the assemblies was far from spontaneous. Remarkably, it was possible to dry the AuNPs assemblies and to solubilize them back with HS-PEGs, improving the colorimetric signal generation. We used this system for protease sensing in biological fluid. Trypsin was chosen as model enzyme and highly positively charged peptides were conjugated to HS-PEG molecules as cleavage substrate. The increase of positive charge of the HS-PEG-peptide conjugate quenched the dissociation capacity of the HS-PEG molecules which could only be restored by the proteolytic cleavage. Picomolar limit of detection was obtained as well as the detection in saliva or urine. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/508454v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@13a6f3org.highwire.dtl.DTLVardef@35b42dorg.highwire.dtl.DTLVardef@1c8249forg.highwire.dtl.DTLVardef@dc8236_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

The diversity of the glycan shield of sarbecoviruses closely related to SARS-CoV-2

The animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the impact of SARS-CoV-2. Vaccines remain successful at limiting severe disease and death, however the continued emergence of SARS-CoV-2 variants, together with the potential for further coronavirus zoonosis, motivates the search for pan-coronavirus vaccines that induce broadly neutralizing antibodies. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of several sarbecovirus glycan shields. Many N-linked glycan attachment sites are shared by all sarbecoviruses, and the processing state of certain sites is highly conserved. However, there are significant differences in the processing state at several glycan sites that surround the receptor binding domain. Our studies reveal similarities and differences in the glycosylation of sarbecoviruses and show how subtle changes in the protein sequence can have pronounced impacts on the glycan shield.

biochemistry↗

bioRxiv2022

multiMiAT: An optimal microbiome-based association test for multicategory phenotypes

Microbes affect the metabolism, immunity, digestion and other aspects of the human body incessantly, and dysbiosis of the microbiome drives not only the occurrence but also the development of disease (i.e., multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g., disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the excellent performance of our method. multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer development and the association between the gut microbiome and diverse development statuses of Clostridium difficile infections.

genetics↗

bioRxiv2022

Goal-specific brain MRI harmonization

There is significant interest in pooling magnetic resonance image (MRI) data from multiple datasets to enable mega-analysis. Harmonization is typically performed to reduce heterogeneity when pooling MRI data across datasets. Most MRI harmonization algorithms do not explicitly consider downstream application performance during harmonization. However, the choice of downstream application might influence what might be considered as study-specific confounds. Therefore, ignoring downstream applications during harmonization might potentially limit downstream performance. Here we propose a goal-specific harmonization framework that utilizes downstream application performance to regularize the harmonization procedure. Our framework can be integrated with a wide variety of harmonization models based on deep neural networks, such as the recently proposed conditional variational autoencoder (cVAE) harmonization model. Three datasets from three different continents with a total of 2787 participants and 10085 anatomical T1 scans were used for evaluation. We found that cVAE removed more dataset differences than the widely used ComBat model, but at the expense of removing desirable biological information as measured by downstream prediction of mini mental state examination (MMSE) scores and clinical diagnoses. On the other hand, our goal-specific cVAE (gcVAE) was able to remove as much dataset differences as cVAE, while improving downstream cross-sectional prediction of MMSE scores and clinical diagnoses.

neuroscience↗

bioRxiv2022

Bile Acid Restrained T Cell Activation Explains Cholestasis Aggravated Hepatitis B Virus Infection

Cholestasis is a common complication of Hepatitis B Virus (HBV) infection, characterized by increased intrahepatic and plasma bile acid levels. Cholestasis was found negatively associated with hepatitis outcome, however; the exact mechanism by which cholestasis impact on anti-viral immunity and impede HBV clearance remains elusive. Here, we found that cholestatic mice are featured with dysfunctional T cell response, and bile acids inhibit the activation and metabolic reprogramming of CD4+ T cells. Mechanistically, bile acids disrupt intracellular calcium homeostasis via inhibiting mitochondria calcium uptake and elevating cytoplasmic Ca2+ concentration of CD4+ T cells, leading to STIM1 and ORAIL1 decoupling and impaired store-operated Ca2+ entry which is essential for NFAT signaling and T cell activation. Moreover, in a transgenic mouse model of HBV infection, it was confirmed that cholestasis compromised T cells activation resulting in poor viral clearance. Collectively, our results suggest that bile acids play pivotal roles in anti-HBV infection via controlling T cells activation and metabolism, and that targeting regulation of bile acids may be a therapeutic strategy for host virus defense.

immunology↗

bioRxiv2022

GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance

The ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non- self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA- based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.

cell biology↗

bioRxiv2022

A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance

Anxiety over perceived threats triggers avoidance behavior, but the underlying neural circuit mechanism remains poorly understood. Taking hints from the deep connection between anxiety and predator defense, we examined the role of the anterior hypothalamic nucleus (AHN), a critical node in the predator defense network, in anxiety-related behaviors. By recording Ca2+ transients in behaving mice, we found that activity of AHN GABAergic (AHNVgat+) neurons showed individually stable increases when animals approached unfamiliar objects in an open field (OF) or explored the open arm of an elevated plus-maze (EPM). Moreover, AHNVgat+ neuron activity foreshadowed behavioral retreats and correlated with object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons dramatically reduced avoidance behaviors. Furthermore, retrograde viral tracing identified the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors. Thus, the activity of the hippocampal-hypothalamic pathway promotes idiosyncratic anxiety-related behavioral avoidance.

neuroscience↗

bioRxiv2022

Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells

Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation. Here, we reveal that bAPs fail to evoke calcium influx through voltage-gated calcium channels (VGCCs) in a specific population of dendritic branches in cortical layer 2/3 pyramidal cells, despite evoking substantial VGCC-mediated calcium influx in sister branches. These branches contain VGCCs and successfully propagate bAPs in the absence of synaptic input; nevertheless, they fail to exhibit bAP-evoked calcium influx due to a branch-specific reduction in bAP amplitude. We demonstrate that these branches have more elaborate branch structure compared to sister branches, which causes a local reduction in electrotonic impedance and bAP amplitude. Finally, we show that bAPs still amplify synaptically-mediated calcium influx in these branches because of differences in the voltage-dependence and kinetics of VGCCs and NMDA-type glutamate receptors. Branch-specific compartmentalization of bAP-dependent calcium signals may provide a mechanism for neurons to diversify synaptic tuning across the dendritic tree.

neuroscience↗

bioRxiv2021

A novel cholinergic neural pathway and its role in the drug relapse

The lateral parabrachial nucleus (LPB) is critical hub implicated in the control of food intake, reward and aversion. Here, we identified a novel cholinergic projection from choline acetyltransferase (ChAT)-positive neurons in external portion of the lateral parabrachial nucleus (eLPBChAT) to {gamma}-aminobutyric acid (GABA) neurons in central nucleus of amygdala (CeAGABA), activation of which could block methamphetamine (METH)-primed conditioned place preference (CPP) in mice.

neuroscience↗

bioRxiv2021

Broccoli sprout Sulforaphane affected hemodynamics and aorta myogenic spontaneous rhythmic contraction in sanitized water uptake mice

Drinking seawater erodes water source will lead to hemodynamic changes in cardiovascular system. The erosion affected vascular biomechanics further interrupt the blood supply in arterial network. In this study, we investigated the carotid arterial hemodynamics in salinity water fed mice, and the relative spontaneous contraction of aorta preparation. The biological effect of Broccoli sprout Sulforaphane was assessed in intake hemodynamic changes. Kunming mice were randomly divided into seawater feeding group, seawater + Sulforaphane group, freshwater feeding group, fresh water + Sulforaphane group. After 4 weeks of feeding, the pressure waveforms of common carotid artery were analyzed in vivo. The enhanced common carotid arterial pressures were calculated according to the breakpoint of systolic pressure rising phase. The ejection time was calculated according to the dicrotic notch. In vitro, the isolated aorta biomechanical features were tested on a micro stepping platform. The passive tension and relative myogenic spontaneous contraction were evaluated. The results indicated that in salinity water fed mice heart rate, ejection period were significantly accelerated. The systolic pressure breakpoint of the ascending phase was significantly increased; however, the central aortic pressure augment index was decreased. In vitro study, the isolated aorta preparations indicated remarkable myogenic spontaneous contraction in salinity water fed mice. The spontaneous contraction indicated a significant cycle pattern, the waveform cluster changes regularly in one cycle, maximal amplitude of myogenic autonomic contraction increased significantly. Spontaneous contraction became more active, however cycle duration shortened. In biological effect of Broccoli sprout supplement, Sulforaphane was effective in reducing the heart rate, prolonging ejection period, improving systolic pressure and pulse pressure amplitude in salinity water fed mice. We concluded that long-term salinity water uptake can form a new hypertension model in mice, which can affect the changes of carotid artery hemodynamics and local blood supply. The Broccoli sprout Sulforaphane can improve the high systolic blood pressure and ejection period of artery, and its mechanism needs further study.

physiology↗

bioRxiv2020

Quaternary climate change explains global patterns of tree beta-diversity

Both historical and contemporary environmental conditions determine present biodiversity patterns, but their relative importance is not well understood. One way to disentangle their relative effects is to assess how different dimensions of beta-diversity relate to past climatic changes, i.e., taxonomic, phylogenetic and functional compositional dissimilarity, and their components generated by replacement of species, lineages and traits (turnover) and richness changes (nestedness). Here, we quantify global patterns of each of these aspects of beta-diversity among neighboring sites for angiosperm trees using the most extensive global database of tree species-distributions (43,635 species). We found that temperature change since the Last Glacial Maximum (LGM) was the major influence on both turnover and nestedness components of beta-diversity, with a negative correlation to turnover and a positive correlation to nestedness. Moreover, phylogenetic and functional nestedness was higher than expected from taxonomic beta-diversity in regions that experienced large temperature changes since the LGM. This pattern reflects relatively greater losses of phylogenetic and functional diversity in species-poor assemblages, possibly caused by phylogenetically and functionally selective species extinction and recolonization during glacial-interglacial oscillations. Our results send a strong warning that rapid anthropogenic climate change is likely to result in a long-lasting phylogenetic and functional compositional simplification, potentially impairing forest ecosystem functioning.

ecology↗

bioRxiv2020

Evaluation of azithromycin or hydroxychloroquine plus azithromycin combination therapy on cardiac conduction and function in guinea pigs

BackgroundIn the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs. MethodsThirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening). ResultsAlthough AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9. ConclusionsAccording to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.

physiology↗

bioRxiv2020

Longitudinal multi-omics along gingivitis development reveal a suboptimal-health gum state with periodontitis-like microbiome

Most adults experience episodes of gingivitis, which can progress to the irreversible, chronic state of periodontitis. However the mechanistic roles of plaque in gingivitis onset and progression to periodontitis remain elusive. Here, we integrated the longitudinal multi-omics data from plaque metagenome, metabolome and salivary cytokines in 40 adults who transit from naturally-occurring gingivitis (NG), to healthy gingivae (baseline) and then to experimental gingivitis (EG). During EG, rapid and consistent alterations in plaque microbiota, metabolites and salivary cytokines emerged as early as 24-72 hours after pause of oral hygiene, defining an asymptomatic sub-optimal health (SoH) stage. SoH also features a steep and synergetic decrease of plaque-derived betaine and Rothia spp., suggesting an anti-gum-inflammation mechanism by health-promoting microbial residents. Global, cross-cohort meta-analysis revealed a high Microbiome-based Periodontitis Index at SoH state, due to its convergent taxonomical and functional profiles towards those of periodontitis. In contrast, caries SoH features a microbial signature very distinct from caries. Thus SoH is a universal state of polymicrobial inflammations with disease-specific features, which is key to maintaining a disease-preventive plaque.

microbiology↗

bioRxiv2020

Meta-matching: a simple framework to translate phenotypic predictive models from big to small data

There is significant interest in using brain imaging data to predict non-brain-imaging phenotypes in individual participants. However, most prediction studies are underpowered, relying on less than a few hundred participants, leading to low reliability and inflated prediction performance. Yet, small sample sizes are unavoidable when studying clinical populations or addressing focused neuroscience questions. Here, we propose a simple framework - "meta-matching" - to translate predictive models from large-scale datasets to new unseen non-brain-imaging phenotypes in boutique studies. The key observation is that many large-scale datasets collect a wide range inter-correlated phenotypic measures. Therefore, a unique phenotype from a boutique study likely correlates with (but is not the same as) some phenotypes in some large-scale datasets. Meta-matching exploits these correlations to boost prediction in the boutique study. We applied meta-matching to the problem of predicting non-brain-imaging phenotypes using resting-state functional connectivity (RSFC). Using the UK Biobank (N = 36,848), we demonstrated that meta-matching can boost the prediction of new phenotypes in small independent datasets by 100% to 400% in many scenarios. When considering relative prediction performance, meta-matching significantly improved phenotypic prediction even in samples with 10 participants. When considering absolute prediction performance, meta-matching significantly improved phenotypic prediction when there were least 50 participants. With a growing number of large-scale population-level datasets collecting an increasing number of phenotypic measures, our results represent a lower bound on the potential of meta-matching to elevate small-scale boutique studies.

neuroscience↗

bioRxiv2020

Spatial and temporal context jointly modulate the sensory response within the ventral visual stream

Both spatial and temporal context play an important role in visual perception and behavior. Humans can extract statistical regularities from both forms of context to help processing the present and to construct expectations about the future. Numerous studies have found reduced neural responses to expected stimuli compared to unexpected stimuli, for both spatial and temporal regularities. However, it is largely unclear whether and how these forms of context interact. In the current fMRI study, thirty-three human volunteers were exposed to object stimuli that could be expected or surprising in terms of their spatial and temporal context. We found a reliable independent contribution of both spatial and temporal context in modulating the neural response. Specifically, neural responses to stimuli in expected compared to unexpected contexts were suppressed throughout the ventral visual stream. Interestingly, the modulation by spatial context was stronger in magnitude and more reliable than modulations by temporal context. These results suggest that while both spatial and temporal context serve as a prior that can modulate sensory processing in a similar fashion, predictions of spatial context may be a more powerful modulator in the visual system. Significance StatementBoth temporal and spatial context can affect visual perception, however it is largely unclear if and how these different forms of context interact in modulating sensory processing. When manipulating both temporal and spatial context expectations, we found that they jointly affected sensory processing, evident as a suppression of neural responses for expected compared to unexpected stimuli. Interestingly, the modulation by spatial context was stronger than that by temporal context. Together, our results suggest that spatial context may be a stronger modulator of neural responses than temporal context within the visual system. Thereby, the present study provides new evidence how different types of predictions jointly modulate perceptual processing.

neuroscience↗

bioRxiv2020

A Computer-aided Method for Identifying the Presence of Softwood Growth Ring Boundaries

ABSTRACTThe objective of this study was to develop a computer-aided method to quantify the obvious degree of growth ring boundaries of softwood species, based on data analysis with some image processing technologies. For this purpose, a 5× magnified cross-section color micro-image of softwood was cropped into 20 sub-images, then every image is binarized as a gray image according to an automatic threshold value. After that, the number of black pixels in the gray image was counted row by row and the number of black pixels was binarized to 0 or 100. Finally, a transition band from earlywood to latewood on the sub-image was identified. If this was successful, the growth ring boundaries of the sub-image are distinct, otherwise they were indistinct or absent. If 10 of the 20 sub-images are distinct, with the majority voting method, the growth ring boundaries of softwood are distinct, otherwise they are indistinct or absent. The proposed method has been visualized as a growth-ring-boundary detecting system based on the .NET Framework. A sample of 100 micro-images (Supplementary Images) of softwood cross-sections were selected for evaluation purposes. In short, this detecting system computes the obvious degree of growth ring boundaries of softwood species by image processing involved image importing, image cropping, image reading, image grayscale, image binarization, data analysis. The results showed that the method used avoided mistakes made by the manual comparison method of identifying the presence of growth ring boundaries, and it has a high accuracy of 98%.View Full Text

plant biology↗

bioRxiv2020

Paleoclimate and current climate collectively shape the phylogenetic and functional diversity of trees worldwide

Trees are of vital importance for ecosystem functioning and services at local to global scales, yet we still lack a detailed overview of the global patterns of tree diversity and the underlying drivers, particularly the imprint of paleoclimate. Here, we present the high-resolution (110 km) worldwide mapping of tree species richness, functional and phylogenetic diversities based on [~]7 million quality-assessed occurrences for 46,752 tree species (80.5% of the estimated total number of tree species), and subsequent assessments of the influence of paleo-climate legacies on these patterns. All three tree diversity dimensions exhibited the expected latitudinal decline. Contemporary climate emerged as the strongest driver of all diversity patterns, with Pleistocene and deeper-time (>107 years) paleoclimate as important co-determinants, and, notably, with past cold and drought stress being linked to reduced current diversity. These findings demonstrate that tree diversity is affected by paleoclimate millions of years back in time and highlight the potential for tree diversity losses from future climate change.

ecology↗