Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year.With the new understanding of the molecular mechanism(s)...Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year.With the new understanding of the molecular mechanism(s)of disease progression,our knowledge about the disease is snowballing,leading to the evolution of many new therapeutic regimes and their successive trials.In the past few decades,various combinations of therapies have been pro-posed and are presently employed in the treatment of diverse cancers.Targeted drug therapy,immunotherapy,and personalized medicines are now largely being employed,which were not common a few years back.The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies,extending patients’disease-free survival thereafter.Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine,chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient’s physical and psychological health.Chemother-apeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons.The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals;it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.展开更多
Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyc...Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyclohydrolase I）, involved in maintaining nitric oxide synthetase （NOS） function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans Combined with previously published data, we demonstrated many GCHI variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.展开更多
In the published article,there was an error in the affiliation information about the first author Uttpal Anand[a].Instead of"Department of Life Sciences,Ben-Gurion University of the Negev,Beer-Sheva 84105,Israel&...In the published article,there was an error in the affiliation information about the first author Uttpal Anand[a].Instead of"Department of Life Sciences,Ben-Gurion University of the Negev,Beer-Sheva 84105,Israel",it should be"CytoGene Research&Development LLP,K-51,UPSIDA Industrial Area,Kursi Road(Lucknow),Dist.Barabanki,225001,Uttar Pradesh,India".The authors would like to apologize for any inconvenience caused and state that this does not change the scientific conclusions of thearticle inanyway.展开更多
Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity an...Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.展开更多
Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(AR...Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.展开更多
Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains mu...Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.展开更多
Context: The gut microbiota represents a complex ecosystem encompassing all unicellular microorganisms residing in the digestive tract, primarily bacteria, fungi, archaea, and even viruses. The relationship between th...Context: The gut microbiota represents a complex ecosystem encompassing all unicellular microorganisms residing in the digestive tract, primarily bacteria, fungi, archaea, and even viruses. The relationship between the host and the microbiota is symbiotic: bacteria benefit from a stable environment, while the host gains numerous capabilities in terms of digestion, metabolism, nutrition, and immunity. However, numerous studies suggest that the gut microbiota plays a crucial role in various non-communicable diseases, including obesity, chronic inflammatory bowel diseases, allergic and immune disorders, behavioral disorders, and even certain cancers. The objective of our study was to characterize the gut microbiota of a group of breast cancer patients by comparing it to that of control subjects in Côte d’Ivoire, using a metagenomic approach. Method: A case-control study was conducted from May 2020 to September 2023. A total of 85 women (39 cases and 46 controls) were recruited, and stool samples were collected from both breast cancer patients and healthy women. Among these, ten (10) samples from patients and ten (10) samples from healthy women were randomly selected for the study of the gut microbiota. The gut microbiota was characterized by sequencing the V4 region of 16S rRNA using metagenomic NGS technology, and bioinformatic analysis was performed using the mothur pipeline. Results: In women with breast cancer, we observed a reduction in the relative abundance of the phyla Firmicutes and Bacteroidetes, as well as an increase in the phyla Actinobacteria and Verrucomicrobia. Additionally, their microbiota exhibited lower Chao1 and Sobs diversities compared to the control women (p < 0.05). Molecular variance analysis (AMOVA) revealed a significant difference between the case and control groups (p < 0.001). This study has highlighted a significant difference in the relative abundance of major phyla within the gut microbiota of cases compared to healthy controls. It will contribute to enriching African and global 展开更多
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand ...Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic levels.These data were complemented with transcriptomics analysis for 39 cases.Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and MLLGB.MLLGA presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples.MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other cases.Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB.The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to treatment.In summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia.These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.展开更多
Background:Genotyping by sequencing(GBS)still has problems with missing genotypes.Imputation is important for using GBS for genomic predictions,especially for low depths,due to the large number of missing genotypes.Mi...Background:Genotyping by sequencing(GBS)still has problems with missing genotypes.Imputation is important for using GBS for genomic predictions,especially for low depths,due to the large number of missing genotypes.Minor allele frequency(MAF)is widely used as a marker data editing criteria for genomic predictions.In this study,three imputation methods(Beagle,IMPUTE2 and FImpute software)based on four MAF editing criteria were investigated with regard to imputation accuracy of missing genotypes and accuracy of genomic predictions,based on simulated data of livestock population.Results:Four MAFs(no MAF limit,MAF≥0.001,MAF≥0.01 and MAF≥0.03)were used for editing marker data before imputation.Beagle,IMPUTE2 and FImpute software were applied to impute the original GBS.Additionally,IMPUTE2 also imputed the expected genotype dosage after genotype correction(GcIM).The reliability of genomic predictions was calculated using GBS and imputed GBS data.The results showed that imputation accuracies were the same for the three imputation methods,except for the data of sequencing read depth(depth)=2,where FImpute had a slightly lower imputation accuracy than Beagle and IMPUTE2.GcIM was observed to be the best for all of the imputations at depth=4,5 and 10,but the worst for depth=2.For genomic prediction,retaining more SNPs with no MAF limit resulted in higher reliability.As the depth increased to 10,the prediction reliabilities approached those using true genotypes in the GBS loci.Beagle and IMPUTE2 had the largest increases in prediction reliability of 5 percentage points,and FImpute gained 3 percentage points at depth=2.The best prediction was observed at depth=4,5 and 10 using GcIM,but the worst prediction was also observed using GcIM at depth=2.Conclusions:The current study showed that imputation accuracies were relatively low for GBS with low depths and high for GBS with high depths.Imputation resulted in larger gains in the reliability of genomic predictions for GBS with lower depths.These results suggest that the ap展开更多
The root system is a major determinant of a plant's access to water and nutrients.The architecture of the root system to a large extent depends on the repeated formation of new lateral roots.In this review,we disc...The root system is a major determinant of a plant's access to water and nutrients.The architecture of the root system to a large extent depends on the repeated formation of new lateral roots.In this review,we discuss lateral root development from a systems biology perspective.We focus on studies combining experiments with computational modeling that have advanced our understanding of how the auxin-centered regulatory modules involved in different stages of lateral root development exert their specific functions.Moreover,we discuss how these regulatory networks may enable robust transitions from one developmental stage to the next,a subject that thus far has received limited attention.In addition,we analyze how environmental factors impinge on these modules,and the different manners in which these environmental signals are being integrated to enable coordinated developmental decision making.Finally,we provide some suggestions for extending current models of lateral root development to incorporate multiple processes and stages.Only through more comprehensive models we can fully elucidate the cooperative effects of multiple processes on later root formation,and how one stage drives the transition to the next.展开更多
Dental primary afferent(DPA)neurons and proprioceptive mesencephalic trigeminal nucleus(MTN)neurons,located in the trigeminal ganglion and the brainstem,respectively,are essential for controlling masticatory functions...Dental primary afferent(DPA)neurons and proprioceptive mesencephalic trigeminal nucleus(MTN)neurons,located in the trigeminal ganglion and the brainstem,respectively,are essential for controlling masticatory functions.Despite extensive transcriptomic studies on various somatosensory neurons,there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation.Here,we employed high-depth single-cell RNA sequencing(scRNA-seq)in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons.Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment,some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth.Furthermore,we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles.Additionally,DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels,receptors,neuropeptides,and mechanoreceptors.Together,our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.展开更多
As a group,the halophilic archaea(class Halobacteria)are the most salt-requiring and salt-resistant microorganisms within the domain Archaea.Halophilic archaea flourish in thalassohaline and athalassohaline environmen...As a group,the halophilic archaea(class Halobacteria)are the most salt-requiring and salt-resistant microorganisms within the domain Archaea.Halophilic archaea flourish in thalassohaline and athalassohaline environments and require over 100–150 g/L NaCl for growth and structural stability.Natural hypersaline environments vary in salt concentration,chemical composition and pH,and occur in climates ranging from tropical to polar and even under-sea.Accordingly,their resident haloarchaeal species vary enormously,as do their individual population compositions and community structures.These diverse halophilic archaeal strains are precious resources for theoretical and applied research but assessing their taxonomic and metabolic novelty and diversity in natural environments has been technically difficult up until recently.Environmental DNA-based high-throughput sequencing technology has now matured sufficiently to allow inexpensive recovery of massive amounts of sequence data,revealing the distribution and community composition of halophilic archaea in different hypersaline environments.While cultivation of haloarchaea is slow and tedious,and only recovers a fraction of the natural diversity,it is the conventional means of describing new species,and provides strains for detailed study.As of the end of May 2020,the class Halobacteria contains 71 genera and 275 species,49.8%of which were first isolated from the marine salt environment and 50.2%from the inland salt environment,indicating that both thalassohaline and athalassohaline environments contain diverse halophilic archaea.However,there remain taxa that have not yet been isolated in pure culture,such as the nanohaloarchaea,which are widespread in the salt environment and may be one of the hot spots in the field of halophilic archaea research in the future.In this review,we focus on the cultivation strategies that have been used to isolate extremely halophilic archaea and point out some of the pitfalls and challenges.展开更多
Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscle...Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes 展开更多
Background:A novel data-driven Boolean model,namely,the fundamental Boolean model(FBM),has been proposed to draw genetic regulatory insights into gene activation,inhibition,and protein decay,published in 2018.This nov...Background:A novel data-driven Boolean model,namely,the fundamental Boolean model(FBM),has been proposed to draw genetic regulatory insights into gene activation,inhibition,and protein decay,published in 2018.This novel Boolean model facilitates the analysis of the activation and inhibition pathways.However,the novel model does not handle the situation well,where genetic regulation might require more time steps to complete.Methods:Here,we propose extending the fundamental Boolean modelling to address the issue that some gene regulations might require more time steps to complete than others.We denoted this extension model as the temporal fundamental Boolean model(TFBM)and related networks as the temporal fundamental Boolean networks(TFBNs).The leukaemia microarray datasets downloaded from the National Centre for Biotechnology Information have been adopted to demonstrate the utility of the proposed TFBM and TFBNs.Results:We developed the TFBNs that contain 285 components and 2775 Boolean rules based on TFBM on the leukaemia microarray datasets,which are in the form of short-time series.The data contain gene expression measurements for 13 GC-sensitive children under therapy for acute lymphoblastic leukaemia,and each sample has three time points:0 hour(before GC treatment),6/8 hours(after GC treatment)and 24 hours(after GC treatment).Conclusion:We conclude that the proposed TFBM unlocks their predecessor’s limitation,Le.,FBM,that could help pharmaceutical agents identify any side effects on clinic-related data.New hypotheses could be identified by analysing the extracted fundamental Boolean networks and analysing their up-regulatory and down-regulatory pathways.展开更多
Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used fo...Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program,AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry.AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.展开更多
RNA sequencing(RNA-seq) has greatly facilitated the exploring of transcriptome landscape for diverse organisms.However,transcriptome reconstruction is still challenging due to various limitations of current tools and ...RNA sequencing(RNA-seq) has greatly facilitated the exploring of transcriptome landscape for diverse organisms.However,transcriptome reconstruction is still challenging due to various limitations of current tools and sequencing technologies.Here,we introduce an efficient tool,QuaPra(Quadratic Programming combined with Apriori),for accurate transcriptome assembly and quantification.QuaPra could detect at least 26.5% more low abundance(0.1–1 FPKM) transcripts with over 2.7% increase of sensitivity and precision on simulated data compared to other currently popular tools.Moreover,around one-quarter more known transcripts were correctly assembled by QuaPra than other assemblers on real sequencing data.QuaPra is freely available at http://www.megabionet.org/QuaPra/.展开更多
Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like pro...Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like protein HLA-DM(DM)catalyzes the exchange and loading of peptides onto MHCⅡmolecules,thereby shaping MHCⅡimmunopeptidomes.Natural variations of DM in both chains of the protein(DMA and DMB)have been hypothesized to impact peptide presentation,but no evidence for altered function has been reported.Here we define the presence of DM allotypes in human populations covered by the 1000 Genomes Project and probe their activity.The functional properties of several allotypes are investigated and show strong enhancement of peptide-induced T cell activation for a particular combination of DMA and DMB.Biochemical evidence suggests a broader pH activity profile for the new variant relative to that of the most commonly expressed DM allotype.Immunopeptidome analysis indicates that the compartmental activity of the new DM heterodimer extends beyond the late endosome and suggests that the natural variation of DM has profound effects on adaptive immunity when antigens bypass the canonical processing pathway.展开更多
Growth rate is a widely studied parameter for various cell-based biological studies.Growth rates of cell populations can be monitored in chemostats and micro-chemostats,where nutrients are continuously replenished.Her...Growth rate is a widely studied parameter for various cell-based biological studies.Growth rates of cell populations can be monitored in chemostats and micro-chemostats,where nutrients are continuously replenished.Here,we present an integrated microfluidic platform that enables long-term culturing of non-adherent cells as well as parallel and mutually independent continuous monitoring of(i)growth rates of cells by means of impedance measurements and of(ii)specific other cellular events by means of high-resolution optical or fluorescence microscopy.Yeast colonies were grown in a monolayer under culturing pads,which enabled high-resolution microscopy,as all cells were in the same focal plane.Upon cell growth and division,cells leaving the culturing area passed over a pair of electrodes and were counted through impedance measurements.The impedance data could then be used to directly determine the growth rates of the cells in the culturing area.The integration of multiple culturing chambers with sensing electrodes enabled multiplexed long-term monitoring of growth rates of different yeast strains in parallel.As a demonstration,we modulated the growth rates of engineered yeast strains using calcium.The results indicated that impedance measurements provide a label-free readout method to continuously monitor the changes in the growth rates of the cells without compromising high-resolution optical imaging of single cells.展开更多
The human body is populated by a large number of microbial colonies,with an estimated 10-100 trillion microbes.The total genome size of human microbial colonies by far overwhelms the size of the host’s genome.This he...The human body is populated by a large number of microbial colonies,with an estimated 10-100 trillion microbes.The total genome size of human microbial colonies by far overwhelms the size of the host’s genome.This heterogenous group of microbial colonies(primarily bacteria,but also archaea,eukaryotes and viruses)is referred to with the term microbiota,and although most of them populate the gut,microbes are also detectable in many other organs of the body,especially in the distal tracts of the genitourinary system and the skin.Over the last years,an increasing amount of evidence has been accumulated on how the microbiota exerts a significant influence on the development and physiology of the human body.展开更多
基金funded by"Agencia Canaria de Inves-tigación,Innovación y Sociedad de la Información(ACIISI)del Gobierno de Canarias"(No.ProID2020010134),óCaja Canarias(Project No.2019SP43).
文摘Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year.With the new understanding of the molecular mechanism(s)of disease progression,our knowledge about the disease is snowballing,leading to the evolution of many new therapeutic regimes and their successive trials.In the past few decades,various combinations of therapies have been pro-posed and are presently employed in the treatment of diverse cancers.Targeted drug therapy,immunotherapy,and personalized medicines are now largely being employed,which were not common a few years back.The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies,extending patients’disease-free survival thereafter.Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine,chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient’s physical and psychological health.Chemother-apeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons.The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals;it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou.,31501013 to HZ and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyclohydrolase I）, involved in maintaining nitric oxide synthetase （NOS） function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans Combined with previously published data, we demonstrated many GCHI variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.
文摘In the published article,there was an error in the affiliation information about the first author Uttpal Anand[a].Instead of"Department of Life Sciences,Ben-Gurion University of the Negev,Beer-Sheva 84105,Israel",it should be"CytoGene Research&Development LLP,K-51,UPSIDA Industrial Area,Kursi Road(Lucknow),Dist.Barabanki,225001,Uttar Pradesh,India".The authors would like to apologize for any inconvenience caused and state that this does not change the scientific conclusions of thearticle inanyway.
基金The lab of AK obtained support from the Interdisciplinary Center for Clinical Research(IZKF)Jena(MSPProject ID:MSP09)+2 种基金DG and MJA B were supported by the Circular Vision project,which has received funding from the European Union's Horizon 2020 research and innovation program(Grant agreement No.899417)the Ministerio de Ciencia e Innovoción,Spain(Grant No.PID2020-119715GB-I00/AEI/10.13039/501100011033)the Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATAMP)(to MJAB)。
文摘Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.
基金supported by the National Key Research and Development Program of China(2023YFC2706503)the National Natural Science Foundation of China(32370720)+9 种基金Beihang University&Capital Medical University Plan(BHME-201904)the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE,ECNU,Key Laboratory of MEA,Ministry of Education,ECNU,Key Laboratory of Ecology and Energy Saving Study of Dense Habitat(Tongji University),Ministry of Education-Shanghai Tongji Urban Planning&Design Institute Co.,Ltd Joint Research Project(KY-2022-LH-A03)Shanghai Tongji Urban Planning&Design Institute Co.,Ltd-China Intelligent Urbanization Co-creation Center for High Density Region Research Project(KY-2022-PT-A02)the Irma T.Hirschl and Monique Weill-Caulier Charitable TrustsBert L and N Kuggie Vallee Foundationthe World Quant FoundationThe Pershing Square Sohn Cancer Research Alliancethe National Institutes of Health(R01AI151059)the National Science Foundation(1840275)the Alfred P.Sloan Foundation(G-2015-13964)。
文摘Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.
基金supported by the Leukemia and Lymphoma Society (Grants No.LLS 9238-16 and MCL7001-18)the National Institutes of Health (Grants No.P01CA214274,R01CA249054 and R01MH117406)the WorldQuant Foundation,NASA (Grants No.80NSSC19K0432,80NSSC22K0254,NNH18ZTT001N-FG2,NNX13AE45G,NNX14AH50G,NNX17AB26G).
文摘Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.
文摘Context: The gut microbiota represents a complex ecosystem encompassing all unicellular microorganisms residing in the digestive tract, primarily bacteria, fungi, archaea, and even viruses. The relationship between the host and the microbiota is symbiotic: bacteria benefit from a stable environment, while the host gains numerous capabilities in terms of digestion, metabolism, nutrition, and immunity. However, numerous studies suggest that the gut microbiota plays a crucial role in various non-communicable diseases, including obesity, chronic inflammatory bowel diseases, allergic and immune disorders, behavioral disorders, and even certain cancers. The objective of our study was to characterize the gut microbiota of a group of breast cancer patients by comparing it to that of control subjects in Côte d’Ivoire, using a metagenomic approach. Method: A case-control study was conducted from May 2020 to September 2023. A total of 85 women (39 cases and 46 controls) were recruited, and stool samples were collected from both breast cancer patients and healthy women. Among these, ten (10) samples from patients and ten (10) samples from healthy women were randomly selected for the study of the gut microbiota. The gut microbiota was characterized by sequencing the V4 region of 16S rRNA using metagenomic NGS technology, and bioinformatic analysis was performed using the mothur pipeline. Results: In women with breast cancer, we observed a reduction in the relative abundance of the phyla Firmicutes and Bacteroidetes, as well as an increase in the phyla Actinobacteria and Verrucomicrobia. Additionally, their microbiota exhibited lower Chao1 and Sobs diversities compared to the control women (p < 0.05). Molecular variance analysis (AMOVA) revealed a significant difference between the case and control groups (p < 0.001). This study has highlighted a significant difference in the relative abundance of major phyla within the gut microbiota of cases compared to healthy controls. It will contribute to enriching African and global
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
基金We thank Adrian Kontor for technical help with the manipulation of AML primary samples,Sarah Mueller for managing the supply of AML primary samples,Janet Matthews for assisting with the processing of patient clinical data,Ruth Osuntola for technical assistance with the mass spectrometry experiments and the FIMM High Throughput Biomedicine Unit for their expert technical support.This work was mainly funded by Cancer Research UK(C15966/A24375)with additional contribution from Blood Cancer UK(20008).All authors have read and approved the article.
文摘Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic levels.These data were complemented with transcriptomics analysis for 39 cases.Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and MLLGB.MLLGA presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples.MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other cases.Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB.The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to treatment.In summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia.These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.
基金This study was funded by the Genomic Selection in Animals and Plants(GenSAP)research project financed by the Danish Council of Strategic Research(Aarhus,Denmark).Xiao Wang received Ph.D.stipends from the Technical University of Denmark(DTU Bioinformatics and DTU Compute),Denmark,and the China Scholarship Council,China.
文摘Background:Genotyping by sequencing(GBS)still has problems with missing genotypes.Imputation is important for using GBS for genomic predictions,especially for low depths,due to the large number of missing genotypes.Minor allele frequency(MAF)is widely used as a marker data editing criteria for genomic predictions.In this study,three imputation methods(Beagle,IMPUTE2 and FImpute software)based on four MAF editing criteria were investigated with regard to imputation accuracy of missing genotypes and accuracy of genomic predictions,based on simulated data of livestock population.Results:Four MAFs(no MAF limit,MAF≥0.001,MAF≥0.01 and MAF≥0.03)were used for editing marker data before imputation.Beagle,IMPUTE2 and FImpute software were applied to impute the original GBS.Additionally,IMPUTE2 also imputed the expected genotype dosage after genotype correction(GcIM).The reliability of genomic predictions was calculated using GBS and imputed GBS data.The results showed that imputation accuracies were the same for the three imputation methods,except for the data of sequencing read depth(depth)=2,where FImpute had a slightly lower imputation accuracy than Beagle and IMPUTE2.GcIM was observed to be the best for all of the imputations at depth=4,5 and 10,but the worst for depth=2.For genomic prediction,retaining more SNPs with no MAF limit resulted in higher reliability.As the depth increased to 10,the prediction reliabilities approached those using true genotypes in the GBS loci.Beagle and IMPUTE2 had the largest increases in prediction reliability of 5 percentage points,and FImpute gained 3 percentage points at depth=2.The best prediction was observed at depth=4,5 and 10 using GcIM,but the worst prediction was also observed using GcIM at depth=2.Conclusions:The current study showed that imputation accuracies were relatively low for GBS with low depths and high for GBS with high depths.Imputation resulted in larger gains in the reliability of genomic predictions for GBS with lower depths.These results suggest that the ap
文摘The root system is a major determinant of a plant's access to water and nutrients.The architecture of the root system to a large extent depends on the repeated formation of new lateral roots.In this review,we discuss lateral root development from a systems biology perspective.We focus on studies combining experiments with computational modeling that have advanced our understanding of how the auxin-centered regulatory modules involved in different stages of lateral root development exert their specific functions.Moreover,we discuss how these regulatory networks may enable robust transitions from one developmental stage to the next,a subject that thus far has received limited attention.In addition,we analyze how environmental factors impinge on these modules,and the different manners in which these environmental signals are being integrated to enable coordinated developmental decision making.Finally,we provide some suggestions for extending current models of lateral root development to incorporate multiple processes and stages.Only through more comprehensive models we can fully elucidate the cooperative effects of multiple processes on later root formation,and how one stage drives the transition to the next.
文摘Dental primary afferent(DPA)neurons and proprioceptive mesencephalic trigeminal nucleus(MTN)neurons,located in the trigeminal ganglion and the brainstem,respectively,are essential for controlling masticatory functions.Despite extensive transcriptomic studies on various somatosensory neurons,there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation.Here,we employed high-depth single-cell RNA sequencing(scRNA-seq)in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons.Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment,some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth.Furthermore,we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles.Additionally,DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels,receptors,neuropeptides,and mechanoreceptors.Together,our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
基金This work was financially supported by the National Natural Science Foundation of China(No.31770005,32070003)the National Science and Technology Fundamental Resources Investigation Program of China(No.2017FY100302,2019FY100700).
文摘As a group,the halophilic archaea(class Halobacteria)are the most salt-requiring and salt-resistant microorganisms within the domain Archaea.Halophilic archaea flourish in thalassohaline and athalassohaline environments and require over 100–150 g/L NaCl for growth and structural stability.Natural hypersaline environments vary in salt concentration,chemical composition and pH,and occur in climates ranging from tropical to polar and even under-sea.Accordingly,their resident haloarchaeal species vary enormously,as do their individual population compositions and community structures.These diverse halophilic archaeal strains are precious resources for theoretical and applied research but assessing their taxonomic and metabolic novelty and diversity in natural environments has been technically difficult up until recently.Environmental DNA-based high-throughput sequencing technology has now matured sufficiently to allow inexpensive recovery of massive amounts of sequence data,revealing the distribution and community composition of halophilic archaea in different hypersaline environments.While cultivation of haloarchaea is slow and tedious,and only recovers a fraction of the natural diversity,it is the conventional means of describing new species,and provides strains for detailed study.As of the end of May 2020,the class Halobacteria contains 71 genera and 275 species,49.8%of which were first isolated from the marine salt environment and 50.2%from the inland salt environment,indicating that both thalassohaline and athalassohaline environments contain diverse halophilic archaea.However,there remain taxa that have not yet been isolated in pure culture,such as the nanohaloarchaea,which are widespread in the salt environment and may be one of the hot spots in the field of halophilic archaea research in the future.In this review,we focus on the cultivation strategies that have been used to isolate extremely halophilic archaea and point out some of the pitfalls and challenges.
基金supported by the National Natural Science Foundation of China (No.31772574)the Program of National Beef Cattle and Yak Industrial Technology System (CARS-37)the scholarship from the China Scholarship Council (CSC),China。
文摘Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes
文摘Background:A novel data-driven Boolean model,namely,the fundamental Boolean model(FBM),has been proposed to draw genetic regulatory insights into gene activation,inhibition,and protein decay,published in 2018.This novel Boolean model facilitates the analysis of the activation and inhibition pathways.However,the novel model does not handle the situation well,where genetic regulation might require more time steps to complete.Methods:Here,we propose extending the fundamental Boolean modelling to address the issue that some gene regulations might require more time steps to complete than others.We denoted this extension model as the temporal fundamental Boolean model(TFBM)and related networks as the temporal fundamental Boolean networks(TFBNs).The leukaemia microarray datasets downloaded from the National Centre for Biotechnology Information have been adopted to demonstrate the utility of the proposed TFBM and TFBNs.Results:We developed the TFBNs that contain 285 components and 2775 Boolean rules based on TFBM on the leukaemia microarray datasets,which are in the form of short-time series.The data contain gene expression measurements for 13 GC-sensitive children under therapy for acute lymphoblastic leukaemia,and each sample has three time points:0 hour(before GC treatment),6/8 hours(after GC treatment)and 24 hours(after GC treatment).Conclusion:We conclude that the proposed TFBM unlocks their predecessor’s limitation,Le.,FBM,that could help pharmaceutical agents identify any side effects on clinic-related data.New hypotheses could be identified by analysing the extracted fundamental Boolean networks and analysing their up-regulatory and down-regulatory pathways.
基金supported by the Strategic Priority Research Program (Grant No. XDB13040100)Key Research Program of Frontier Sciences (Grant No. QYZDJ-SSWSYS009) of the Chinese Academy of Sciences+5 种基金the National Natural Science Foundation (Grant Nos. 91731303,31771388, and 31711530221)the National Science Fund for Distinguished Young Scholars (Grant No. 31525014)the Program of Shanghai Academic Research Leader (Grant No. 16XD1404700)the National Key R&D Program (Grant No. 2016YFC0906403)the Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01), Chinathe support of the ‘‘Ten-Thousand Talents” Program for Young Top-notch Talents, China
文摘Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program,AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry.AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.
基金supported by the National High Technology Research and Development Program of China(2015AA020108)the National Key Research and Development Program of China(2016YFC0902100)+2 种基金the China Human Proteome Project(2014DFB30010,2014DFB30030)the National Science Foundation of China(31671377,31401133,31771460,91629103)the Program of Introducing Talents of Discipline to Universities of China(B14019)
文摘RNA sequencing(RNA-seq) has greatly facilitated the exploring of transcriptome landscape for diverse organisms.However,transcriptome reconstruction is still challenging due to various limitations of current tools and sequencing technologies.Here,we introduce an efficient tool,QuaPra(Quadratic Programming combined with Apriori),for accurate transcriptome assembly and quantification.QuaPra could detect at least 26.5% more low abundance(0.1–1 FPKM) transcripts with over 2.7% increase of sensitivity and precision on simulated data compared to other currently popular tools.Moreover,around one-quarter more known transcripts were correctly assembled by QuaPra than other assemblers on real sequencing data.QuaPra is freely available at http://www.megabionet.org/QuaPra/.
基金supported by the Deutsche Forschungsgemeinschaft(DFG)C.F.is thankful for funding by the DFG(FR-1325/17–1,SFB958(project Z03)+1 种基金TRR186(projects A05,A11))M.A.-B.is thankful for funding from the Freie Universität Berlin Forschungskommision.
文摘Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like protein HLA-DM(DM)catalyzes the exchange and loading of peptides onto MHCⅡmolecules,thereby shaping MHCⅡimmunopeptidomes.Natural variations of DM in both chains of the protein(DMA and DMB)have been hypothesized to impact peptide presentation,but no evidence for altered function has been reported.Here we define the presence of DM allotypes in human populations covered by the 1000 Genomes Project and probe their activity.The functional properties of several allotypes are investigated and show strong enhancement of peptide-induced T cell activation for a particular combination of DMA and DMB.Biochemical evidence suggests a broader pH activity profile for the new variant relative to that of the most commonly expressed DM allotype.Immunopeptidome analysis indicates that the compartmental activity of the new DM heterodimer extends beyond the late endosome and suggests that the natural variation of DM has profound effects on adaptive immunity when antigens bypass the canonical processing pathway.
基金The work was financially supported by the Swiss SystemsX.ch IPhD program,by the FP7 of the EU through the MTN ISOLATE,Contract Number 289995the Ambizione Grant 142440 of the Swiss National Science Foundation for Olivier Frey.
文摘Growth rate is a widely studied parameter for various cell-based biological studies.Growth rates of cell populations can be monitored in chemostats and micro-chemostats,where nutrients are continuously replenished.Here,we present an integrated microfluidic platform that enables long-term culturing of non-adherent cells as well as parallel and mutually independent continuous monitoring of(i)growth rates of cells by means of impedance measurements and of(ii)specific other cellular events by means of high-resolution optical or fluorescence microscopy.Yeast colonies were grown in a monolayer under culturing pads,which enabled high-resolution microscopy,as all cells were in the same focal plane.Upon cell growth and division,cells leaving the culturing area passed over a pair of electrodes and were counted through impedance measurements.The impedance data could then be used to directly determine the growth rates of the cells in the culturing area.The integration of multiple culturing chambers with sensing electrodes enabled multiplexed long-term monitoring of growth rates of different yeast strains in parallel.As a demonstration,we modulated the growth rates of engineered yeast strains using calcium.The results indicated that impedance measurements provide a label-free readout method to continuously monitor the changes in the growth rates of the cells without compromising high-resolution optical imaging of single cells.
基金supported by Templeton World Charity Foundation Independent Research Fellowship to CHR(TWCF0241&TWCF0503).
文摘The human body is populated by a large number of microbial colonies,with an estimated 10-100 trillion microbes.The total genome size of human microbial colonies by far overwhelms the size of the host’s genome.This heterogenous group of microbial colonies(primarily bacteria,but also archaea,eukaryotes and viruses)is referred to with the term microbiota,and although most of them populate the gut,microbes are also detectable in many other organs of the body,especially in the distal tracts of the genitourinary system and the skin.Over the last years,an increasing amount of evidence has been accumulated on how the microbiota exerts a significant influence on the development and physiology of the human body.
