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Liu, H.

Publications and source records attributed to Liu, H..

At least 973 records · Page 54Linked to original sources

BIOTIN ATTACHMENT DOMAIN-CONTAINING proteins, inhibitors of ACCase, are regulated by WRINKLED1

WRINKLED1 (WRI1) is a transcriptional activator that binds to AW boxes in the promoters of many genes from central metabolism and FA synthesis, resulting in their transcription. BIOTIN ATTACHMENT DOMAIN-CONTAINING (BADC) proteins are homologs of BIOTIN CARBOXYL CARRIER PROTEIN (BCCP) that lack a biotin-attachment domain and are therefore inactive. In the presence of excess FA, BADC1 and BADC3 are primarily responsible for the observed long-term irreversible inhibition of ACETYL-COA CARBOXYLASE (ACCase), and consequently FA synthesis. Purified WRI1 bound with high affinity (Kds in the low nanomolar range) to canonical AW-boxes from the promoters of all three BADC genes. Consistent with this observation, the expression of BADC1, BADC2 and BADC3 genes and BADC1 protein levels were reduced in wri1-1 relative to wild type (WT), and BADCs gene expression and BADC1 protein levels also were elevated upon WRI1 overexpression. The double mutant badc1badc2 phenocopied wri1-1 with respect to both reduction in root length, and elevation of indole-3-acetic acid-Asp (IAA-Asp) levels relative to WT. Overexpression of BADC1 in wri1-1 decreased its IAA-Asp and partially rescued its short-root phenotype demonstrating a role for BADCs in seedling establishment. That WRI1 positively regulates genes encoding both FA synthesis and BADCs i.e., conditional inhibitors of FA synthesis, represents a coordinated mechanism to achieve lipid homeostasis in which plants couple the transcription their FA synthetic capacity with their capacity to biochemically downregulate it.\n\nOne sentence summaryWRI1 regulates genes encoding both fatty acid synthesis and inhibitors of FA synthesis (BADCs), creating a lipid homeostatic mechanism in which the transcription of FA synthetic capacity is coordinated with the capacity to biochemically downregulate FA synthesis.

plant biology↗

Powerful solution for experimental cerebral malaria treatment: artesunate and tetramethylpyrazine

BackgroundCerebral malaria (CM) is a kind of serious neurological complication caused by the acute Plasmodium falciparum infection. About 300000 patients including children under 5 years old died from this disease every year. Even intravenous artesunate (Art) is employed as the most effictive drug in the treatment of CM, high incidence of death and neurological sequelae are still inevitable. Therefore, we assessed the combination of Art and tetramethylpyrazine (TMP), to treat experimental CM (ECM) in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). A non-biased whole brain quantitative proteomic analysis was also conducted to get some insight of the mechanism of the combinational treatment.\n\nResultsTreatment of (ECM)-C57BL/6 mice with the combination of Art and TMP increased the survival, improved clinical signs and prevented neurological manifestations. These effects were related to reduction of parasitised red blood cells (pRBC) adhesion, sequestration, maintaining brain microvascular integrity, increasing nerve growth factor, neurotrophin levels, and alleviating hippocampal neuronal damage and astrocyte activation. The pharmacological effects of Art-TMP combination therapy were analyzed by ECM mice brain proteomic function enrichment. Based on an isobaric tag for relative and absolute quantitation (iTRAQ) fold-change of 1.2 (P-value < 0.05), 217 down-regulated and 177 up-regulated proteins were identified, presenting a significantly altered proteome profile of the combined Art and TMP group as compared to the group treated with Art or TMP alone. These results suggested that the Art-TMP combination could be used as a powerful solution for CM and its neurologic damage.\n\nConclusionsAn effictive therapy for CM with low mortality rate and protect against ECM-induced neurocognitive impairment has been proposed through the combination of Art and TMP, which can provide an effective adjuvant treatment in the clinic. iTRAQ proteomics provide a resource for further mechanistic studies to examine the synergistic effects of Art and TMP and their potential to serve as an adjunctive treatment method and intervention targets.\n\nAuthor SummaryCerebral malaria (CM) is the most serious neurological complication caused by Plasmodium falciparum infection. Even after antimalarial treatment, severe neurological sequelae still exist. We used tetramethylpyrazine (TMP), the main ingredient of the traditional Chinese medicine Chuanxiong, and artesunate (Art) as a combination of drugs. We found that Art-TMP combination could improve the clinical symptoms of CM and protect the nervous system. At the same time, proteomics was used to analyze the protective mechanism of Art-TMP combination administration on ECM mice. This study suggests that the combination of Art and TMP may be used as an adjuvant therapy for clinical CM and iTRAQ proteomics provides resources for further study of Art-TMP combination and provides potential prognostic biomarkers for this therapeutic intervention.

pathology↗

Identification of neuronal lineages in the Drosophila peripheral nervous system with a novel multi-spectral lineage tracing system

Elucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale of lineage tracing but eliminate the spatial information offered by conventional approaches. Multispectral labeling techniques, such as Brainbow, have the potential to identify lineage-related cells in situ. Here, we report Lineage Tracker Bitbow, a \"digital\" version of Brainbow that greatly expands the color diversity, and a suite of statistical methods for quantifying the lineage relationship of any two cells. Applying these tools to Drosophila peripheral nervous system, we determined lineage relationship between all neuronal pairs. Based on the refined lineage map, we explored whether distinct cis-regulatory elements are used in controlling the expression of a terminal selector gene in distinct lineage patterns. This study demonstrates LT-Bitbow as an efficient tool for in-situ lineage mapping and its potential in studying molecular mechanisms in the lineage context.

neuroscience↗

Engineering acetyl-CoA metabolic shortcut for eco-friendly production of polyketides triacetic acid lactone in Yarrowia lipolytica

Acetyl-CoA is the central metabolic node connecting glycolysis, Krebs cycle and fatty acids synthase. Plant-derived polyketides, are assembled from acetyl-CoA and malonyl-CoA, represent a large family of biological compounds with diversified bioactivity. Harnessing microbial bioconversion is considered as a feasible approach to large-scale production of polyketides from renewable feedstocks. Most of the current polyketide production platform relied on the lengthy glycolytic steps to provide acetyl-CoA, which inherently suffers from complex regulation with metabolically-costly cofactor/ATP requirements. Using the simplest polyketide triacetic acid lactone (TAL) as a target molecule, we demonstrate that acetate uptake pathway in oleaginous yeast (Yarrowia lipolytica) could function as an acetyl-CoA shortcut to achieve metabolic optimality in producing polyketides. We identified the metabolic bottlenecks to rewire acetate utilization for efficient TAL production in Y. lipolytica, including generation of the driving force for acetyl-CoA, malonyl-CoA and NADPH. The engineered strain, with the overexpression of endogenous acetyl-CoA carboxylase (ACC1), malic enzyme (MAE1) and a bacteria-derived cytosolic pyruvate dehydrogenase (PDH), affords robust TAL production with titer up to 4.76 g/L from industrial glacier acetic acid in shake flasks, representing 8.5-times improvement over the parental strain. The acetate-to-TAL conversion ratio (0.149 g/g) reaches 31.9% of the theoretical maximum yield. The carbon flux through this acetyl-CoA metabolic shortcut exceeds the carbon flux afforded by the native acetyl-CoA pathways. Potentially, acetic acid could be manufactured in large-quantity at low-cost from Syngas fermentation or heterogenous catalysis (methanol carbonylation). This alternative carbon sources present a metabolic advantage over glucose to unleash intrinsic pathway limitations and achieve high carbon conversion efficiency and cost-efficiency. This work also highlights that low-cost acetic acid could be sustainably upgraded to high-value polyketides by oleaginous yeast species in an eco-friendly and cost-efficient manner.

bioengineering↗

The coordinate actions of calcineurin and Hog1 mediate the response to cellular stress through multiple nodes of the cell cycle network

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between diverse stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the stress-activated phosphatase calcineurin (CN) in this process and show that CN utilizes multiple pathways to control the cell cycle. Upon activation, CN inhibits transcription factors (TFs) that regulate the G1/S transition through activation of the stress-activated MAPK Hog1. In contrast, CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner at multiple nodes of the cell cycle-regulatory network to rewire gene expression and arrest cells in response to stress. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.

cell biology↗

Characterization of aroma-active compounds in delicious apples juices by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O) and odor activity value (OAV)

Volatile aroma compounds of delicious apple juice in three cultivars were obtained by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), and GC-flame photometric detection (FPD). Quantitatively, the major volatiles of the delicious apple juice were detected by GC-MS, such as esters, alcohols, aldehydes. In addition, GC-O and OAV were used to determine the aroma-active compounds in fruit. Amongst these compounds, ethyl 2-methylbutanoate (47-229), butyl 2-methylbutanoate (8-208), (E)-2-hexenal (25-120), butyl propanoate (14-54), methyl 2-methylbutanoate (28-41), ethyl hexanoate (4-32), ethyl butanoate (5-17) showed high OAVs in three delicious apple juices, which contributed greatly to the aroma of delicious apple juice. Beside those compounds, methanethiol (OAV: 1.1-1.6), dimethyl sulfide (OAV: 2.5-3.6), methional (OAV: 4.2-11.7) and 2-(methylthio)ethanol (OAV: 1.2-1.9) also presented relatively high OAVs. Finally, four compounds (ethyl 2-methylbutanoate, ethyl octanoate, ethyl butanoate and ethyl hexanoate) were selected to investigate the possible interactions occurring in the delicious apple juice. The resultants demonstrated that those aroma volatile compounds can decrease threshold of the solution to dissimilar degrees before and after their addition.

biochemistry↗

CRISPR-Cas9 screening of KSHV-transformed cells identifies XPO1 as a vulnerable target of cancer cells

The abnormal proliferation of cancer cells is driven by deregulated oncogenes or tumor suppressors, of which the cancer vulnerable genes are attractive therapeutic targets. Targeting mislocalization of oncogenes and tumor suppressors resulting from aberrant nuclear export is effective for inhibiting growth transformation of cancer cells. We performed a CRISPR-Cas9 screening in a unique model of matched primary and oncogenic KSHV-transformed cells, and identified genes that were pro-growth and growth-suppressive of both cells, of which exportin XPO1 was demonstrated to be critical for the survival of transformed cells. Using XPO1 inhibitor KPT-8602 and by siRNA knockdown, we confirmed the essential role of XPO1 in cell proliferation and growth transformation of KSHV-transformed cells, and cell lines of other cancers including gastric cancer and liver cancer. XPO1 inhibition induced cell cycle arrest through p53 activation but the mechanism of p53 activation differed among different types of cancer cells. p53 activation depended on the formation of PML nuclear bodies in gastric cancer and liver cancer cells. Mechanistically, XPO1 inhibition induced relocalization of autophagy adaptor protein p62 (SQSTM1), recruiting p53 for activation in PML nuclear bodies. Taken together, we have identified novel pro-growth and growth-suppressive genes of primary and cancer cells, and demonstrated XPO1 as a vulnerable target of cancer cells. XPO1 inhibition induces cell arrest through a novel PML-and p62-dependent mechanism of p53 activation in some types of cancer cells.\n\nImportanceUsing a model of oncogenic virus KSHV driven cellular transformation of primary cells, we have performed a genome-wide CRISPR-Cas9 screening to identify vulnerable genes of cancer cells. This screening is unique in that this virus-induced oncogenesis model does not depend on any cellular genetic alterations, and has matched primary and KSHV-transformed cells, which are not available for similar screenings in other types of cancer. We have identified genes that are both pro-growth and growth-suppressive in primary and transformed cells, some of which could represent novel proto-oncogenes and tumor suppressors. In particular, we have demonstrated exportin XPO1 as a critical factor for the survival of transformed cells. Using a XPO1 inhibitor KPT-8602 and by siRNA-mediated knockdown, we have confirmed the essential role of XPO1 in cell proliferation and growth transformation of KSHV-transformed cells, as well as gastric and liver cancer cells. XPO1 inhibition induces cell cycle arrest by activating p53 but the mechanism of p53 activation differed among different types of cancer cells. p53 activation is dependent on the formation of PML nuclear bodies in gastric and liver cancer cells. Mechanistically, XPO1 inhibition induces relocalization of autophagy adaptor protein p62 (SQSTM1), recruiting p53 for activation in PML nuclear bodies. These results illustrate XPO1 as a vulnerable target of cancer cells, and reveal a novel mechanism for blocking cancer cell proliferation by XPO1 inhibition as well as a novel PML-and p62-mediated mechanism of p53 activation in some types of cancer cells.

cancer biology↗

Understanding the molecular mechanism of umami recognition by T1R1-T1R3 using molecular dynamics simulations

Taste receptor T1R1-T1R3 can be activated by binding to several natural ligands, e.g., L-glutamate and 5-ribonucleotides etc., thereby stimulating the umami taste. The molecular mechanism of umami recognition at an atomic level, however, remains elusive. Here, using homology modeling, molecular docking and molecular dynamics (MD) simulations, we investigate the effects of five natural umami ligands on the structural dynamics of T1R1-T1R3. Our work identifies the key residues that are directly involved in recognizing the binding ligands. In addition, two adjacent binding sites in T1R1 are determined for substrate binding, and depending on the molecular size and chemical properties of the incoming ligand, one or both these binding sites can be occupied. More interestingly, the binding of varied ligands can lead to either closing or opening of T1R1, based on which, we further classify the five ligands into two groups. This different binding effects are likely associated with the distinct umami signals stimulated by various ligands. This work warrants new experimental assays to further validate the theoretical model and provides guidance to design more effective umami ligands.\n\nAuthor summaryUmami, as the fifth basic taste, is induced by umami substances from the natural food, such as L-glutamate, 5-ribonucleotides, and peptides etc. These umami substances are widely added to foods as flavor enhancers to promote food quality. However, although extensive experimental and theoretical studies have been devoted to revealing the recognition mechanisms of the taste receptor T1R1-T1R3 to the umami ligands, the detailed molecular mechanism is still unknown, largely due to the lack of the receptor structure. Here, using a new template structure different from the former theoretical studies, we constructed a more accurate homology model of T1R1-T1R3. Based on this receptor model, combined with molecular docking and MD simulations, we investigate how different ligands with varied molecular size and chemical groups might affect the dynamics of T1R1. Our work provides the structural basis for relating the dynamics of umami receptor induced by varied ligands to the resulting umami signal.

molecular biology↗

On the energetics and stability of a minimal fish school

The physical basis for fish schooling is examined using three-dimensional numerical simulations of a pair of swimming fish, with kinematics and geometry obtained from experimental data. Energy expenditure and efficiency are evaluated using a cost of transport function, while the effect of schooling on the stability of each swimmer is examined by probing the lateral force and the lateral and longitudinal force fluctuations. We construct full maps of the aforementioned quantities as functions of the spatial pattern of the swimming fish pair and show that both energy expenditure and stability can be invoked as possible reasons for the swimming patterns and tail-beat synchronization observed in real fish. Our results suggest that high cost of transport zones should be avoided by the fish. Wake capture may be energetically unfavorable in the absence of kinematic adjustment. We hereby hypothesize that fish may restrain from wake capturing and, instead, adopt side-to-side configuration as a conservative strategy, when the conditions of wake energy harvesting are not satisfied. To maintain a stable school configuration, compromise between propulsive efficiency and stability, as well as between school members, ought to be considered.

biophysics↗

Whole genome base-wise aggregation and functional prediction for human non-coding regulatory variants

Predicting the functional or pathogenic regulatory variants in the human non-coding genome facilitates the interpretation of disease causation. While numerous prediction methods are available, their performance is inconsistent or restricted to specific tasks, which raises the demand of developing comprehensive integration for those methods. Here, we compile whole genome base-wise aggregations, regBase, that incorporate largest prediction scores. Building on different assumptions of causality, we train three composite models to score functional, pathogenic and cancer driver non-coding regulatory variants respectively. We demonstrate the superior and stable performance of our models using independent benchmarks and show great success to fine-map causal regulatory variants. We believe that regBase database together with three composite models will be useful in different areas of human genetic studies, such as annotation-based casual variant fine-mapping, pathogenic variant discovery as well as cancer driver mutation identification. regBase is freely available at https://github.com/mulinlab/regBase.

genomics↗

ITGA2 is a target of miR-206 promoting cancer stemness and lung metastasis through enhanced ACLY and CCND1 expression in triple negative breast cancer

Accumulating evidence demonstrates that cancer stemness is essential for both tumor development and progression, regulated by multi-layer factors at genetic, epigenetic and micro-environmental levels. However, how to target stemness-driven plasticity and eliminate metastasis remains one of the biggest challenges in the clinic. We aim to identify novel molecular mechanisms underlying stemness of triple negative breast cancer (TNBC) which frequently metastasizes to the visceral organs but lacks targeted therapies. Following our previous discovery of miR-206 as an epigenetic suppressor of tumorigenesis and metastasis, we now report that the integrin receptor CD49b-encoding ITGA2 is an oncogenic target of miR-206 in TNBC. ITGA2 knockdown abolished cancer stemness (mammosphere formation, pluripotency marker expression, and FAK phosphorylation), inhibited cell cycling, compromised migration and invasion, and thereby decreasing lung metastasis of TNBC. RNA sequencing analyses of breast cancer cells revealed that ITGA2 knockdown inhibits gene expression essential for both classical integrin-regulated pathways (cell cycle, wounding response, protein kinase, etc) and newly identified pathways such as lipid metabolism. Notably, ACLY-encoded ATP citrate lyase is one of the top targets in CD49b-regulated lipid metabolism and CCND1-encoded Cyclin D1 represents regulation of cell cycle and many other pathways. ACLY, known to catalyze the formation of cytosolic acetyl-CoA for fatty acid biosynthesis, is indispensable for cancer stemness. Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest. High expression levels of the ITGA2/ACLY/CCND1 axis are correlated with an unfavorable relapse-free survival of patients with high grade breast cancer, in both basal-like and other subtypes. This study identifies ITGA2 as a potential therapeutic target of TNBC stemness and metastasis.

cancer biology↗

Plasma Circular RNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma

To explore whether plasma circular RNAs (circRNAs) can diagnose hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), microarray and qPCR were used to identify plasma circRNAs that were increased in HCC patients compared with controls (including healthy controls, chronic hepatitis B, HBV-related liver cirrhosis and HCC patients). A logistic regression model was constructed using a training set (n=313) and then validated using another two independent sets (n=306 and 526, respectively). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. We identified a plasma circRNA panel (CircPanel) containing three circRNAs (hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) that could detect HCC. CircPanel showed a higher accuracy than AFP (alpha-fetoprotein) to distinguish individuals with HCC from controls in all three sets (AUC 0.863 [95% CI 0.819-0.907] vs 0.790 [0.738-0.842], P=0.036 in training set; 0.843 [0.796-0.890] vs 0.747 [0.691-0.804], P=0.011 in validation set 1 and 0.864 [0.830-0.898] vs 0.769 [0.728-0.810], P<0.001 in validation set 2). CircPanel also performed well in detecting Small-HCC (solitary, [&le;]3cm), AFP-negative HCC and AFP-negative Small-HCC.\n\nSignificance of this studyWhat is already known about this subject? O_LIThe diagnostic accuracy of alpha-fetoprotein (AFP) in detecting hepatocellular carcinoma (HCC) is unsatisfactory.\nC_LIO_LICircular RNA (circRNA) expression profiles in HCC and adjacent nontumor liver tissues are significantly different.\nC_LIO_LIPlasma circRNAs are enriched, stable and can be biomarkers for various diseases.\nC_LI\n\nWhat are the new findings? O_LIThe expression of circRNAs in the plasma from HCC patients and chronic hepatitis B is significantly different.\nC_LIO_LIPlasma circRNA panel (CircPanel, including hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) has a higher accuracy than AFP to distinguish individuals with HCC or Small-HCC (solitary, [&le;]3cm) from controls (healthy controls, chronic hepatitis B and HBV-related liver cirrhosis).\nC_LIO_LICircPanel also performs well in diagnosing AFP-negative HCC and AFP-negative Small-HCC.\nC_LI\n\nHow might it impact on clinical practice in the foreseeable future? Plasma CircPanel can be a diagnostic biomarker in detecting HCC and improves the diagnostic accuracy.

cancer biology↗

Large-scale chemical-genetics of the human gut bacterium Bacteroides thetaiotaomicron

The genomic catalogue of the human microbiota has expanded dramatically in recent years, and insights derived from human microbiota genomics has vast potential to generate treatments for human diseases. However, predictably harnessing the microbiota for beneficial outcomes is currently limited by our lack of understanding of the physiology of the constituent bacteria. For instance, the functions of most of their genes are not known. Here, we systematically measure mutant phenotypes for genes from the gut commensal Bacteroides thetaiotaomicron. Using a barcoded transposon mutant library, we measured the fitness of 4,055 B. thetaiotaomicron genes across 492 experiments, including growth on 45 carbon substrates and in the presence of 57 stress-inducing compounds. Our data is in strong agreement with previous studies, and more importantly also uncovers the biological roles of poorly annotated genes. We identified 497 genes with a specific phenotype in only one or a handful of conditions, thus enabling informed predictions of gene function for a subset of these genes. For example, we identified a glycoside hydrolase important for growth on type I rhamnogalacturonan, a DUF4861 protein for glycosaminoglycan utilization, a DUF1080 protein for disaccharide utilization, and a tripartite multidrug resistance system specifically important for bile salt tolerance. Our approach can be applied to other members of the human microbiota to experimentally characterize their genes.

microbiology↗

A direct link between Prss53, hair curvature, and skeletal dysplasia

In humans, protease serine S1 family member 53 (Prss53) is highly expressed in the hair follicle, especially the inner root sheath, which is associated with hair shape according to recent genome-wide association study (GWAS) data. However, no animal evidence has indicated a link between Prss53 and hair shape to date. Here, we used CRISPR/Cas9 to generate Prss53-mutated rabbits. The homozygous (Prss53-/-) rabbits exhibited curved hair and skeletal dyskinesia with severe malformation, while the heterozygous (Prss53+/-) rabbits did not exhibit these features. The curvature features of the hair were accompanied by lesions that were generally denser and less well-defined in the cuticular septation of the hair shaft, and the compartments of the hair follicle were incomplete, as evidenced by decreased expression levels of keratinocyte differentiation genes. In addition, skeletal dysplasia, an increased lethality rate and decreased plasma calcium and serum alkaline phosphatase (ALP) levels were determined in the Prss53-/- rabbits. Furthermore, disrupted calcium metabolism, which may play a role in the hair curvature and skeletal dysplasia of Prss53+/- rabbits, was demonstrated by using high-throughput RNA sequencing data. Thus, our study confirmed for the first time that the loss of Prss53 lead to curved hair in animals and provides new insights into the crucial role of Prss53 in calcium metabolism. Author SummaryNo animal evidence has indicated a link between Prss53 and hair shape to date. The Prss53-/- rabbits exhibited curved hair and skeletal dyskinesia. The disrupted calcium metabolism may play a role in the hair curvature and skeletal dysplasia of Prss53+/- rabbits.

genomics↗

OxyR senses reactive sulfane sulfur and activates genes for its removal in Escherichia coli

Reactive sulfane sulfur species such as hydrogen polysulfide and organic persulfide are newly recognized as normal cellular components, involved in signaling and protecting cells from oxidative stress. Their production is extensively studied, but their removal is less characterized. Herein, we showed that reactive sulfane sulfur is toxic at high levels, and it is mainly removed via reduction by thioredoxin and glutaredoxin with the release of H2S in Escherichia coli. OxyR is best known to respond to H2O2, and it also played an important role in responding to reactive sulfane sulfur under both aerobic and anaerobic conditions. It was modified by hydrogen polysulfide to OxyR C199-SSH, which activated the expression of thioredoxin 2 and glutaredoxin 1. This is a new type of OxyR modification. Bioinformatics analysis showed that OxyRs are widely present in bacteria, including strict anaerobic bacteria. Thus, the OxyR sensing of reactive sulfane sulfur may represent a conserved mechanism for bacteria to deal with sulfane sulfur stress.

microbiology↗

Gene pathogenicity prediction of Mendelian diseases via the Random Forest algorithm

The study of Mendelian diseases and the identification of their causative genes are of great significance in the field of genetics. The evaluation of the pathogenicity of genes and the total number of Mendelian disease genes are both important questions worth studying. However, very few studies have addressed these issues to date, so we attempt to answer them in this study. We calculated gene pathogenicity prediction (GPP) score by a machine learning approach (random forest algorithm) to evaluate the pathogenicity of genes. When we applied the GPP score to the testing gene set, we obtained accuracy of 80%, recall of 93% and area under the curve (AUC) of 0.87. Our results estimated that a total of 10,399 protein-coding genes were Mendelian disease genes. Furthermore, we found the GPP score was positively correlated with the severity of disease. Our results indicate that GPP score may provide a robust and reliable guideline to predict the pathogenicity of protein-coding genes. To our knowledge, this is the first trial to estimate the total number of Mendelian disease genes.

genetics↗

Transcranial photobiomodulation with infrared laser increases power of brain oscillations

Non-invasive transcranial photobiomodulation with a 1064-nm laser (tPBML1064) has been reported to improve human performance on cognitive tasks as well as locally upregulate cerebral oxygen metabolism and hemodynamics. However, it is unknown whether tPBML1064 also modulates electrophysiology, and specifically neural oscillations, in the human brain. The hypothesis guiding this study was that tPBML1064 of the right prefrontal cortex enhances neurophysiological rhythms at specific frequency bands in the human brain under resting conditions. To test this hypothesis, we recorded the 64-channel scalp electroencephalogram (EEG) before, during, and after the application of 11 minutes of 4-cm-diameter tPBML1064 to the right forehead of human subjects (n=20) using a within-subject, sham-controlled design. Time-resolved scalp topographies of EEG power at five frequency bands were computed to examine tPBML1064-induced EEG power changes across the scalp. The results showed time-dependent, significant increases of EEG spectral powers at the alpha (8-13 Hz) and beta (13-30 Hz) bands at broad scalp regions, exhibiting a front-to-back pattern. The findings provide the first sham-controlled topographic mapping that tPBML1064 increases the strength of electrophysiological oscillations (alpha and beta bands), while also shedding light on the mechanisms of tPBM in the human brain.

bioengineering↗

Draft genome sequence of the Solanum aethiopicum provides insights into disease resistance, drought tolerance and the evolution of the genome

BackgroundS. aethiopicum is a close relative to S. melongena and has been routinely used to improve disease resistance in S. melongena. However, these efforts have been greatly limited by the lack of a reference genome and the clear understanding of the genes involved during biotic and abiotic stress response. ResultsWe present here a draft genome assembly of S. aethiopicum of 1.02 Gb in size, which is predominantly occupied by repetitive sequences (76.2%), particularly long terminal repeat elements. We annotated 37,681 gene models including 34,905 protein-coding genes. We observed an expansion of resistance genes through two rounds of amplification of LTR-Rs, occurred around 1.25 and 3.5 million years ago, respectively. The expansion also occurred in gene families related to drought tolerance. A number of 14,995,740 SNPs are identified by re-sequencing 65 S. aethiopicum genotypes including "Gilo" and "Shum" accessions, 41,046 of which are closely linked to resistance genes. The domestication and demographic history analysis reveals selection of genes involved in drought tolerance in both "Gilo" and "Shum" groups. A pan-genome of S. aethiopicum with a total of 36,250 protein-coding genes was assembled, of which 1,345 genes are missing in the reference genome. ConclusionsOverall, the genome sequence of S. aethiopicum increases our understanding of the genomic mechanisms of its extraordinary disease resistance and drought tolerance. The SNPs identified are available for potential use by breeders. The information provided here will greatly accelerate the selection and breeding of the African eggplant as well as other crops within the Solanaceae family.

genomics↗