Biology subjects

Liu, W.

Publications and source records attributed to Liu, W..

At least 505 records · Page 28Linked to original sources

bioRxiv2020

RNA-binding protein Syncrip regulates Starvation-Induced Hyperactivity in adult Drosophila

How to respond to starvation determines fitness. One prominent behavioral response is increased locomotor activities upon starvation, also known as Starvation-Induced Hyperactivity (SIH). SIH is paradoxical as it promotes food seeking but also increases energy expenditure. Despite its importance in fitness, the genetic contributions to SIH as a behavioral trait remains unexplored. Here, we examined SIH in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association studies. We identified 23 significant loci, corresponding to 14 genes, significantly associated with SIH in adult Drosophila. Gene enrichment analyses indicated that genes encoding ion channels and mRNA binding proteins (RBPs) were most enriched in SIH. We are especially interested in RBPs because they provide a potential mechanism to quickly change protein expression in response to environmental challenges. Using RNA interference, we validated the role of syp in regulating SIH. syp encodes Syncrip (Syp), an RBP. While ubiquitous knockdown of syp led to semi-lethality in adult flies, adult flies with neuron-specific syp knockdown were viable and exhibited decreased SIH. Using the Temporal and Regional Gene Expression Targeting (TARGET) system, we further confirmed the role of Syp in adult neurons in regulating SIH. To determine how syp is regulated by starvation, we performed RNA-seq using the heads of flies maintained under either food or starvation conditions. RNA-seq analyses revealed that syp was alternatively spliced under starvation while its expression level was unchanged. We further generated an alternatively-spliced-exon-specific knockout (KO) line and found that KO flies showed reduced SIH. Together, this study demonstrates a significant genetic contribution to SIH as a behavioral trait, identifies syp as a SIH gene, and highlights the significance of RBPs and post-transcriptional processes in the brain in regulating behavioral responses to starvation. Author summaryAnimals living in the wild often face periods of starvation. How to physiologically and behaviorally respond to starvation is essential for survival. One behavioral response is Starvation-Induced Hyperactivity (SIH). We used the Drosophila melanogaster Genetic Reference Panel, derived from a wild population, to study the genetic basis of SIH. Our results show that there is a significant genetic contribution to SIH in this population, and that genes encoding RNA binding proteins (RBPs) are especially important. Using RNA interference and the TARGET system, we confirmed the role of an RBP Syp in adult neurons in SIH. Using RNA-seq and Western blotting, we found that syp was alternatively spliced under starvation while its expression level was unchanged. Further studies from syp exon-specific knockout flies showed that alternative splicing involving two exons in syp was important for SIH. Together, this study identifies syp as a SIH gene and highlights an essential role of post-transcriptional modification in regulating this behavior.

genomics↗

bioRxiv2019

Detection of genome-wide low-frequency mutations with Paired-End and Complementary Consensus Sequencing (PECC-Seq) revealed end-repair derived artifacts as residual errors

To improve the accuracy and the cost-efficiency of next-generation sequencing in ultralow-frequency mutation detection, we developed the Paired-End and Complementary Consensus Sequencing (PECC-Seq), a PCR-free duplex consensus sequencing approach. PECC-Seq employed shear points as endogenous barcodes to identify consensus sequences from the overlap in the shortened, complementary DNA strands-derived paired-end reads for sequencing error correction. With the high accuracy of PECC-Seq, we identified the characteristic base substitution errors introduced by the end-repair process of mechanical fragmentation-based library preparations, which were prominent at the terminal 6 bp of the library fragments in the 5-NpCpA-3 or 5-NpCpT-3 trinucleotide context. As demonstrated at the human genome scale (TK6 cells), after removing these potential end-repair artifacts from the terminal 6 bp, PECC-Seq could reduce the sequencing error frequency to mid-10-7 with a relatively low sequencing depth. For TA base pairs, the background error rate could be suppressed to mid-10-8. In mutagen-treated TK6, slight increases in mutagen treatment-related mutant frequencies could be detected, indicating the potential of PECC-Seq in detecting genome-wide ultra-rare mutations. In addition, our finding on the patterns of end-repair artifacts may provide new insights in further reducing technical errors not only for PECC-Seq, but also for other next-generation sequencing techniques.

genomics↗

bioRxiv2019

Staphylococcus aureus staphyloxanthin expression is not controlled by Hfq

ObjectiveThe golden color of Staphylococcus aureus is due to the synthesis of carotenoid pigments. In Gram-negative bacteria, Hfq is a global posttranscriptional regulator, but its function in S. aureus remains obscure. The absence of Hfq in S. aureus was reported to correlate with production of carotenoid pigment leading to the conclusion that Hfq was a negative regulator of the yellow color. However, we reported the construction of hfq mutants in several S. aureus strains and never noticed any color change; we therefore revisited the question of Hfq implication in S. aureus pigmentation. ResultsThe absence or accumulation of Hfq does not affect S. aureus pigmentation.

microbiology↗

bioRxiv2019

A Registration and Deep Learning Approach to Automated Landmark Detection for Geometric Morphometrics

O_LIGeometric morphometrics is the statistical analysis of landmark-based shape variation and its covariation with other variables. Over the past two decades, the gold standard of landmark data acquisition has been manual detection by a single observer. This approach has proven accurate and reliable in small-scale investigations. However, big data initiatives are increasingly common in biology and morphometrics. This requires fast, automated, and standardized data collection. Image registration, or the spatial alignment of images, is a fundamental technique in automatic image analysis that is well-poised for such purposes. Yet, in the few studies that have explored the utility of registration-based landmarks for geometric morphometrics, relatively high or catastrophic labelling errors around anatomical extrema are common. Such errors can result in misleading representations of the mean shape, an underestimation of biological signal, and altered variance-covariance patterns. C_LIO_LIWe combine image registration with a deep and domain-specific neural network to automate and optimize anatomical landmark detection for geometric morphometrics. Using micro-computed tomography images of genetically and morphologically variable mouse skulls, we test our landmarking approach under a variety of registration conditions, including different non-linear deformation frameworks (small vs. large) and atlas strategies (single vs. multi). C_LIO_LICompared to landmarks derived from conventional image registration workflows, our optimized landmark data show significant reductions in error at problematic locations (up to 0.63 mm), a 36.4% reduction in average landmark coordinate error, and up to a 45.1% reduction in total landmark distribution error. We achieve significant improvements in estimates of the sample mean shape and variance-covariance structure. C_LIO_LIFor biological imaging datasets and morphometric research questions, our method can eliminate the time and subjectivity of manual landmark detection whilst retaining the biological integrity of these expert annotations. C_LI

evolutionary biology↗

bioRxiv2019

Effect of antenatal tetramethylpyrazine on lung development and YAP expression in a rat model of experimental congenital diaphragmatic hernia

Tetramethylpyrazine (TMP) is a chemical compound found in extracts derived from the Chinese medicinal plant. Due to its remarkable therapeutic effects, availability, and low cost and toxicity, TMP has been used to treat cardiovascular diseases and pulmonary hypertension in China. The aim of this study was to investigate the therapeutic effects and underlying mechanism of TMP on lung development using a rat model of nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were divided into three groups: control, CDH, and CDH+TMP. Nitrofen was used to induce CDH. In the CDH and CDH+TMP, Fetuses only with left diaphragmatic hernias were chosen for analysis. Lung and body weight were recorded and lung histologic evaluations, image analysis, and western blot analysis of YAP, p-YAP and LATS1 were performed after lung processing. A marked abnormal structure was observed, as evidenced by pulmonary hypoplasia and vascular remodeling, in the CDH. These abnormalities were improved in the CDH+TMP. There were significant differences between the CDH and CDH+TMP in percentage of medial wall thickness, arteriole muscularization, radial alveolar counts, AA%, and alveolar septal thickness. YAP expression was markedly increased in the CDH compared to the control, which was not affected by antenatal TMP administration. However, prenatal TMP intervention significantly increased expression of LATS1 and phosphorylation of YAP in the CDH fetuses. Our results demonstrate that antenatal TMP administration improved vascular remodeling and promoted lung development in a rat model of CDH, potentially through increasing expression of LATS1 and phosphorylation of YAP.

developmental biology↗

bioRxiv2019

Stress-induced myonectin improves glucose homeostasis by inhibiting glycemic response to HPA axis

Inhibiting glycemic response to HPA axis contributes to glycemic control for diabetic patients. Here, mice were subjected to high-fat diet and intermittent chronic stress, and glucose homeostasis and lipolysis were determined during the intervention. Firstly, we found that glucose intolerance appears at the earliest, followed by reduced insulin sensitivity and increased epinephrine (EPI) sensitivity in the early stage of diet-induced obesity. Next we investigated whether chronic stress impairs glycemic control and which mediates its effects. Short-term stress training raises serum and skeletal muscle myonectin (Myn) levels and improves glucose intolerance. Stress attenuates blood glucose and glycerol responses to EPI, but enhances lipolytic response to EPI in adipose tissues. Myn overexpression in vivo improves glucose tolerance and enhances insulin sensitivity at the cost of blunting glycemic responses to EPI. Myn knockdown reduces beneficial effects of stress or exercise on glucose homeostasis. Together, myonectin is a stress-induced myokine that readjusts glycemic and metabolic responses to HPA axis, and thus prevent the progression of glucose intolerance and obesity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/838003v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@42b09forg.highwire.dtl.DTLVardef@59a744org.highwire.dtl.DTLVardef@1f4a01dorg.highwire.dtl.DTLVardef@13bda27_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryChronic stress breaks glucose intolerance cycle to resist diet-induced obesity, through myonectin-mediated inhibition of glycemic response to epinephrine (EPI) and activation of insulin signaling in adipose tissues. HighlightsO_LIEPI sensitivity increases after glucose intolerance and with reduced insulin sensitivity in diet-induced obesity C_LIO_LIChronic stress blunts glycemic responses to EPI and increases myonectin levels in serum and skeletal muscle C_LIO_LIMyonectin attenuates glycemic response to EPI and improves metabolic profile in HFD-fed mice C_LIO_LIReducing myonectin reverses beneficial effects of stress on glucose homeostasis C_LI

physiology↗

bioRxiv2019

A novel antiviral lncRNA EDAL shields a T309 O-GlcNAcylation site to promote EZH2 degradation

The central nervous system (CNS) is vulnerable for viral infection, yet few host factors in the CNS are known to defend invasion by neurotropic viruses. We report here that multiple neurotropic viruses, including rabies virus (RABV), vesicular stomatitis virus (VSV), Semliki Forest virus (SFV) and herpes simplex virus 1 (HSV-1), elicit the neuronal expression of a host-encoded lncRNA EDAL. EDAL inhibits the replication of these neurotropic viruses in neuronal cells and RABV infection in mouse brains. EDAL binds to the conserved histone methyltransferase enhancer of zest homolog 2 (EZH2) and specifically causes EZH2 degradation via lysosomes, reducing the cellular H3K27me3 level. The antiviral function of EDAL resides in a 56-nt antiviral substructure through which its 18-nt helix-loop intimately contacts multiple EZH2 sites surrounding T309, a known O-GlcNAcylation site. EDAL positively regulate the transcription of Pcp4l1 encoding a 10 kDa peptide, which inhibits the replication of mutiple neurotropic viruses. Our findings proposed a model in which a neuronal lncRNA can exert an effective antiviral function via blocking a specific O-GlcNAcylation that determines EZH2 lysosomal degradation.

microbiology↗

bioRxiv2019

Probing the neural dynamics of mnemonic representations in humans

Memories are not stored as static engrams, but as dynamic representations affected by processes occurring after initial encoding. Previous studies revealed changes in activity and mnemonic representations in visual processing areas, parietal lobe, and hippocampus underlying repeated retrieval and suppression. However, these neural changes are usually induced by memory modulation immediately after memory formation. Here, we investigated 27 healthy participants with a two-day functional Magnetic Resonance Imaging design to probe how established memories are dynamically modulated by retrieval and suppression 24 hours after learning. Behaviorally, we demonstrated that established memories can still be strengthened by repeated retrieval. By contrast, repeated suppression had a modest negative effect, and suppression-induced forgetting was associated with individual suppression efficacy. Neurally, we demonstrated item-specific pattern reinstatements in visual processing areas, parietal lobe, and hippocampus. Then, we showed that repeated retrieval reduced activity amplitude in the ventral visual cortex and hippocampus, but enhanced the distinctiveness of activity patterns in the ventral visual cortex and parietal lobe. Critically, reduced activity was associated with enhanced representation of idiosyncratic memory traces in ventral visual cortex and precuneus. In contrast, repeated memory suppression was associated with the reduced lateral prefrontal activity, but relative intact mnemonic representations. Our results replicated most of the neural changes induced by memory retrieval and suppression immediately after learning and extended those findings to established memories after initial consolidation. Active retrieval seems to promote episode-unique mnemonic representations in the neocortex after initial encoding but also consolidation. HighlightsO_LIRepeated retrieval strengthened consolidated memories, while repeated suppression had a modest negative effect. C_LIO_LIPattern reinstatements of individual memories were detected in the visual area, parietal lobe, and hippocampus after 24 hours. C_LIO_LIAfter repeated retrieval, reduced activity amplitude was associated with increased distinctiveness of activity patterns in the ventral visual cortex and right precuneus. C_LIO_LIRepeated suppression was associated with the reduced lateral prefrontal activity, but unchanged mnemonic representations. C_LI

neuroscience↗

bioRxiv2019

Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

The biology of how faces are built and come to differ from one another is complex. Discovering the genes that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTLs peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.\n\nAuthor SummaryThe mammalian face is a complex structure serving many functions. We studied the genetic basis for facial skeletal diversity in a large sample of mice from an experimental population designed for the study of complex traits. We quantified the contribution of genetic variation to variation in three-dimensional facial shape across more than 55,000 genetic markers spread throughout the mouse genome. We found 37 genetic regions which are very likely to contribute to differences in facial shape. We then conducted a more detailed analysis of the genetic regions associated with the most variable aspects of facial shape. For these regions, a disproportionately large number of genes are known to be important to growth and to skeletal and facial development. The magnitude of these genetic contributions to differences in facial shape are consistently small. Our results therefore support the notion that facial skeletal diversity is influenced by many genes of small effect, but that some of these small effects may be related to genes that are fundamental to skeletal and facial development.

genetics↗

bioRxiv2019

Computational redesign of PETase for plastic biodegradation by GRAPE strategy

The excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 {degrees}C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment.

synthetic biology↗

bioRxiv2019

Predicting 30-day Hospital Readmissions Using Artificial Neural Networks with Medical Code Embedding

Reducing unplanned readmissions is a major focus of current hospital quality efforts. In order to avoid unfair penalization, administrators and policymakers use prediction models to adjust for the performance of hospitals from healthcare claims data. Regression-based models are a commonly utilized method for such risk-standardization across hospitals; however, these models often suffer in accuracy. In this study we, compare four prediction models for unplanned patient readmission for patients hospitalized with acute myocardial infarction (AMI), congestive health failure (HF), and pneumonia (PNA) within the Nationwide Readmissions Database in 2014. We evaluated hierarchical logistic regression and compared its performance with gradient boosting and two models that utilize artificial neural network. We show that unsupervised Global Vector for Word Representations embedding representations of administrative claims data combined with artificial neural network classification models significantly improves prediction of 30-day readmission. Our best models increased the AUC for prediction of 30-day readmissions from 0.68 to 0.72 for AMI, 0.60 to 0.64 for HF, and 0.63 to 0.68 for PNA compared to hierarchical logistic regression. Furthermore, risk-standardized hospital readmission rates calculated from our artificial neural network model that employed embeddings led to reclassification of approximately 10% of hospitals across categories of hospital performance. This finding suggests that prediction models that incorporate new methods classify hospitals differently than traditional regression-based approaches and that their role in assessing hospital performance warrants further investigation.

bioinformatics↗

bioRxiv2019

Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify candidate risk genes and biological pathways

Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children (\"primary\" stereotypies, CMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with CMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging variants in CMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in CMS probands show significant overlap with those in Tourette syndrome, ASD candidate genes, and those in ASD probands with high stereotypy scores. Furthermore, exploratory biological pathway and gene ontology analysis highlight histone demethylation, organism development, cell motility, glucocorticoid receptor pathway, and ion channel transport. Continued sequencing of CMS trios will identify more risk genes and allow greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

genomics↗

bioRxiv2019

CHD8 regulates the balance between proliferation and differentiation of human iPSCs in neural development

BackgroundChromodomain helicase DNA-binding protein 8 (CHD8), which encodes a chromatin remodeling protein that regulates Wnt/{beta}-catenin mediated gene expression, is one of the most strongly associated genes with autism spectrum disorder (ASD). Characterization of ASD patients with CHD8 disrupting mutations and animal and stem cell models of CHD8 deficiency suggest that CHD8 plays a role in neurodevelopment.\n\nMethodsWe generated iPSCs from the T-lymphocytes of a healthy, typically-developing human male and iPSC lines from the same source which were subjected to CRISPR/Cas9-mediated knockdown (KD) of CHD8. We subsequently derived neural progenitor cells (NPCs) and neural cells and examined the effects of CHD8 deficiency on cell proliferation and neural differentiation.\n\nResultsWe observed that, compared to WT, CHD8 KD: (1) increased the number of iPSC colonies formed, (2) suppressed spontaneous differentiation along the edges of iPSC colonies, (3) increased the proliferation of NPCs, (4) delayed the formation of neural rosettes, (5) delayed neurite outgrowth, (6) decreased the percentage of cells in the G0/G1 phase of the cell cycle, (7) increased the percentage of cells in the G2/M phase of the cell cycle, (8) decreased presence of the neuronal marker MAP2 although not the glial marker GFAP, (9) decreased presence for the excitatory neuronal marker VGLUT1, and (10) decreased presence of the synaptic marker SYN1.\n\nConclusionsOur results suggest that CHD8 deficiency causes alterations in the cell cycle. More specifically, CHD8 KD appears to increase cell proliferation and delay neural differentiation. This may contribute to the pathophysiology of ASD.

neuroscience↗

bioRxiv2019

Structure determination from lipidic cubic phase embedded microcrystals by MicroED

The lipidic cubic phase (LCP) technique has proved to facilitate the growth of high-quality crystals that are otherwise difficult to grow by other methods. Because crystals grown in LCP can be limited in size, improved techniques for structure determination from these small crystals are important. Microcrystal electron diffraction (MicroED) is a technique that uses a cryo-TEM to collect electron diffraction data and determine high-resolution structures from very thin micro and nanocrystals. In this work, we have used modified LCP and MicroED protocols to analyze crystals embedded in LCP. Proteinase K in LCP was used as a model system, and several LCP sample preparation strategies were tested. Among these, treatment with 2-Methyl-2,4-pentanediol (MPD) and lipase were both able to reduce the viscosity of the LCP and produce quality cryo-EM grids with well-diffracting crystals. These results set the stage for the use of MicroED to analyze other microcrystalline samples grown in LCP.

biochemistry↗

bioRxiv2019

Genome-wide development of miRNA-based SSR markers in Cleistogenes songorica with their transferability analysis to gramineae and non- gramineae species

SSR markers are commonly used for many genetic applications, such as map construction, fingerprinting and genetic diversity analysis due to their high reproducibility, levels of polymorphism and abundance. As endogenous, small RNAs, miRNAs have essential roles in plant development and gene expression under diverse stress conditions, including various biotic and abiotic stress conditions. In the present study, we predicted 110 pre-miRNAs sequences from 287 precursor miRNAs and used them as queries for SSR marker development. Among 110 primer pairs, 85 were successfully amplified and examined for transferability to other gramineae and non-gramineae species. The results showed that all 82 primer pairs yielded unambiguous and strong amplification, and across the 23 studied Cleistogenes accessions, a total of 385 alleles were polymorphic. The number of alleles produced per primer varied from 3 to 11, with an average of 4.69 per locus. The expected heterozygosity (He) ranged from 0.44 to 0.88, with an average of 0.74 per locus, and the PIC (Polymorphism Information Content) values ranged from 0.34 to 0.87, with an average of 0.69 per locus. In this study, 1422 miRNA target genes were predicted and analyzed using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases. The results showed that this miRNA-based microsatellite marker system can be very useful for genetic diversity and marker-assisted breeding studies.

genomics↗

bioRxiv2019

A landmark-free morphometric pipeline: Application to characterise a Down syndrome model skull phenotype

Characterising phenotypes often requires quantification of anatomical shapes. Quantitative shape comparison (morphometrics) traditionally uses anatomical landmarks and is therefore limited by the number of landmarks and operator accuracy when landmarks are located manually. Here we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome (DS), validating it against a landmark-based approach. We identify cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening) homologous to the human phenotype. The landmark-free phenotyping was less labour-intensive and required less user training than the landmark-based method. It also enabled mapping of local differences as planar expansion or shrinkage. This higher resolution and local mapping pinpointed reductions in interior mid-snout structures and occipital bones in this DS model that were not as apparent using a traditional landmark-based method. This approach could make morphometrics widely-accessible beyond traditional niches in zoology and palaeontology, especially in characterising mutant phenotypes.

genetics↗

bioRxiv2019

Common neural and transcriptional correlates of inhibitory control across emotion, memory, and response inhibition

Inhibitory control is crucial for regulating emotions, and it may also enable memory control. However, evidence for their shared neurobiological correlates is limited. Here, we report meta-analyses of neuroimaging studies on emotion regulation, or memory control, and link neural commonalities to transcriptional commonalities using the Allen Human Brain Atlas (AHBA). Based on 95 fMRI studies, we reveal a role of the right inferior parietal lobule embedded in a frontal-parietal-insular network during emotion and memory control, which is similarly recruited during response inhibition. These co-activation patterns also overlap with the networks associated with "inhibition", "cognitive control", and "working memory" when consulting the Neurosynth. Using the AHBA, we demonstrate that emotion and memory control-related brain activity patterns are associated with transcriptional profiles of a specific set of "inhibition-related" genes. Gene ontology enrichment analysis of these "inhibition-related" genes reveal associations with the neuronal transmission and risk for major psychiatric disorders as well as seizures and alcoholic dependence. In summary, this study identified a neural network and a set of genes associated with inhibitory control across emotion regulation, memory control. These findings facilitate our understanding of the neurobiological correlates of inhibitory control and may contribute to the development of novel brain stimulation and pharmacological interventions.

neuroscience↗

bioRxiv2019

HIV-1 Nef interacts with LMP7 to attenuate immunoproteasome formation and MHC-I antigen presentation

AbstractProteasome is major protein degradation machinery and plays essential roles in diverse biological functions. Upon cytokine inductions, proteasome subunits {beta}1, {beta}2, and {beta}5 are replaced by {beta}1i/LMP2, {beta}2i/MECL-1, and {beta}5i/LMP7, leading to the formation of immunoproteasome. Immunoproteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I) to regulate immune responses and induce cytotoxic-T-lymphocytes (CTLs). Human immunodeficiency virus type 1 (HIV-1) is the causal agent of acquired immunodeficiency syndrome (AIDS). HIV-1-specific CTLs represent critical immune responses to limit viral replication. HIV-1 negative regulatory factor (Nef) counteracts host immunity, especially the MHC-I/CTL. This study reveals a distinct mechanism by which Nef facilitates immune evasion through attenuating the functions of immunoproteasome and MHC-I. Nef interacts with LMP7 on the endoplasmic reticulum (ER) to down-regulate the incorporation of LMP7 into immunoproteasome, and thereby attenuating immunoproteasome formation. Moreover, Nef represses immunoproteasome protein degradation function, MHC-I trafficking, and antigen presentation activity.\n\nImportanceUbiquitin-proteasome system (UPS) is essential for degradation of damaged proteins, which takes place in proteasome. Upon cytokine inductions, proteasome catalytic activities are replaced by distinct isoforms resulting in formation of immunoproteasome. Immunoproteasome generates peptides for MHC-I antigen presentation and plays important roles in immune responses. HIV-1 is the agent of AIDS, and HIV-1-specific CTLs represent immune responses to limit viral replication. This study reveals a distinct mechanism by which HIV-1 promotes immune evasion. Viral protein Nef interacts with immunoproteasome component LMP7 to attenuate immunoproteasome formation and protein degradation function, and repress MHC-I antigen presentation activity. Therefore, HIV-1 targets LMP7 to inhibit immunoproteasome activation and LMP7 may be used as a target for the development of anti-HIV-1/AIDS therapy.

microbiology↗