Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic a...Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic architecture underlying CT biosynthesis in wheat grain remains unclear.Here,we studied the deposition and genetic regulation of CT in wheat grains,and found that CT deposited specifically in the testa layer of red-grained wheat as catechin-and epicatechin-formed polymers.Genome-wide association study identified 22 genetic loci affecting CT content,one of which,TaTAN,a single dominant gene controlling CT presence,was mapped to chromosome 3A in a segregation population.Further pan-genome analysis,transcriptome profiling and ethyl methanesulfonate induced mutants sequencing revealed a R2R3-MYB transcription factor,TaMYB10-3A,as the causal gene.Three loss-of-function alleles in TaMYB10-3A caused by large fragment inversion-deletion and insertion were identified which abolish both CT deposition and red pigmentation,demonstrating the pleiotropic effect of TaMYB10-3A on CT presence and grain color.TaMYB10-3A directly trans-activates core flavonoid genes such as chalcone synthase and dihydroflavonol 4-reductase to initiate CT biosynthesis.Our investigation provides a comprehensive understanding of CT presence in wheat grains and lays a solid foundation for manipulating CT metabolites to improve wheat grain end-use quality and nutrition values in wheat.展开更多
The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferou...The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.展开更多
The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients wi...The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia.We used prepulse inhibition(PPI)and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls.Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions.Concurrently,we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in firstepisode treatment-naı¨ve schizophrenic patients(n=117)and in age-and sex-matched healthy controls(n=86).We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia.Significant correlations between gray matter volumes(GMVs)in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice.Furthermore,these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients.The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients.Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation,providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia.展开更多
Apple replant disease(ARD)is a major limitation to the establishment of economically viable orchards on replant sites due to the buildup and long-term survival of pathogen inoculum.Several soilborne necrotrophic fungi...Apple replant disease(ARD)is a major limitation to the establishment of economically viable orchards on replant sites due to the buildup and long-term survival of pathogen inoculum.Several soilborne necrotrophic fungi and oomycetes are primarily responsible for ARD,and symptoms range from serious inhibition of growth to the death of young trees.Chemical fumigation has been the primary method used for control of ARD,and manipulating soil microbial ecology to reduce pathogen density and aggressiveness is being investigated.To date,innate resistance of apple rootstocks as a means to control this disease has not been carefully explored,partly due to the complex etiology and the difficulty in phenotyping the disease resistance.Molecular defense responses of plant roots to soilborne necrotrophic pathogens are largely elusive,although considerable progress has been achieved using foliar disease systems.Plant defense responses to necrotrophic pathogens consist of several interacting modules and operate as a network.Upon pathogen detection by plants,cellular signals such as the oscillation of Ca^(2+)concentration,reactive oxygen species(ROS)burst and protein kinase activity,lead to plant hormone biosynthesis and signaling.Jasmonic acid(JA)and ethylene(ET)are known to be fundamental to the induction and regulation of defense mechanisms toward invading necrotrophic pathogens.Complicated hormone crosstalk modulates the fine-tuning of transcriptional reprogramming and metabolic redirection,resulting in production of antimicrobial metabolites,enzyme inhibitors and cell wall refortification to restrict further pathogenesis.Transcriptome profiling of apple roots in response to inoculation with Pythium ultimum demonstrated that there is a high degree of conservation regarding the molecular framework of defense responses compared with those observed with foliar tissues.It is conceivable that the timing and intensity of genotype-specific defense responses may lead to different outcomes between rootstocks in response to invasion by necrotrophic pathogens.Elucidation of host defense mechanisms is critical in developing molecular tools for genomics-assisted breeding of resistant apple rootstocks.Due to their perennial nature,use of resistant rootstocks as a component for disease management might offer a durable and cost-effective benefit to tree performance than the standard practice of soil fumigation for control of ARD.展开更多
Although seed oil production and composition are genetically controlled, changes of oil level and oil composition across genotypes and environments such as drought and temperature were observed. The mechanisms of how ...Although seed oil production and composition are genetically controlled, changes of oil level and oil composition across genotypes and environments such as drought and temperature were observed. The mechanisms of how genotypes interact with environment, affecting oil production and composition, are still not well understood. The objective of this research was to investigate the effect of drought/water stress and temperature on soybean genotypes. Two soybean genotypes of maturity group (MG) II (PI 597411 B and PI 597408) and two of MG VI (Arksoy and PI 437726) were used. A repeated greenhouse experiment to study the effect of water stress and a repeated growth chamber experiment to study the effect of temperature were conducted. The results showed that both water stress and high temperature altered seed oil composition by increasing oleic acid and decreasing linoleic and linolenic acid concentrations. Severe water stress (soil water potential between -150 to -200 kPa) or high temperature (40/33℃, day/night) resulted in higher palmitic acid and lower stearic acid. Genotypes differed in their responses to water stress or temperature. Analyses of seed carbohydrates (glucose, fructose, sucrose, raffinose, and stachyose) showed a significant decline of glucose, fructose, and sucrose and a significant increase of stachyose concentration by water stress and high temperature. Analyses of natural abundance of δ15N and δ13C isotopes showed changes in sources of nitrogen and carbon fixation, possibly affecting nitrogen and carbon metabolism pathways. The research demonstrated that both water stress and high temperature altered oil production and composition, and this could be partially related to limited availability and movement of carbohydrates from leaves to seed. Further research to investigate the enzymes controlling fatty acids conversion and nitrogen and carbon metabolism is needed.展开更多
The Dormancy-associated MADS-box(DAM)gene cluster in peach serves as a key regulatory hub on which the seasonal temperatures act and orchestrate dormancy onset and exit,chilling response and floral bud developmental p...The Dormancy-associated MADS-box(DAM)gene cluster in peach serves as a key regulatory hub on which the seasonal temperatures act and orchestrate dormancy onset and exit,chilling response and floral bud developmental pace.Yet,how different temperature regimes interact with and regulate the six linked DAM genes remains unclear.Here,we demonstrate that chilling downregulates DAM1 and DAM3–6 in dormant floral buds with distinct patterns and identify DAM4 as the most abundantly expressed one.We reveal multiple epigenetic events,with tri-methyl histone H3 lysine 27(H3K27me3)induced by chilling specifically in DAM1 and DAM5,a 21-nt sRNA in DAM3 and a ncRNA induced in DAM4.Such induction is inversely correlated with downregulation of their cognate DAMs.We also show that the six DAMs were hypermethylated,associating with the production of 24-nt sRNAs.Hence,the chilling-responsive dynamic of the different epigenetic elements and their interactions likely define distinct expression abundance and downregulation pattern of each DAM.We further show that the expression of the five DAMs remains steadily unchanged or continuously downregulated at the ensuing warm temperature after chilling,and this state of regulation correlates with robust increase of sRNA expression,H3K27me3 and CHH methylation,which is particularly pronounced in DAM4.Such robust increase of repressive epigenetic marks may irreversibly reinforce the chillingimposed repression of DAMs to ensure flower-developmental programming free from any residual DAM inhibition.Taken together,we reveal novel information about genetic and epigenetic regulation of the DAM cluster in peach,which will be of fundamental significance in understanding of the regulatory mechanisms underlying chilling requirement and dormancy release,and of practical application for improvement of plasticity of flower time and bud break in fruit trees to adapt changing climates.展开更多
Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS h...Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN.This systematic overview aims to critically evaluate the latest data reported within the scientific literature.The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors.PubMed,Google Scholar,and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years,reporting studies on the main queries addressed in this work.This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers,clarifying and updating the role of genetic factors in SCCHN onset and development.The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN.展开更多
AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients.METHODS A case study of histologically confirmed ulcerative coli...AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients.METHODS A case study of histologically confirmed ulcerative colitis(UC)or Crohn's disease(CD)patients with≥1 year disease duration,who were compared to unrelated,gender-matched,healthy individuals as controls,was conducted at four major centers in Sri Lanka.Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants:IL12 B:rs1045431,IL23 R:rs11805303,ARPC2:rs12612347,IRGM:rs13361189,IL26/IL22:rs1558744,CDH1:rs1728785,IL10:rs3024505,FCGR2 A:rs3737240,PTGER4:rs4613763,IL17 REL/PIM3:rs5771069,HNF4 a:rs6017342,STAT3:rs744166,SMURF1:rs7809799,LAMB1:rs886774,HLA-DRB5,DQA1,DRB1,DRA:rs9268853,MST1,UBA7,and APEH:rs9822268.The genotypes of all variants were in Hardy-Weinberg Equilibrium(P>10^(-3)).To account for multiple hypothesis testing,P-values<0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited.Out of the single nucleotide polymorphisms(SNPs)tested,the majority were not associated with IBD in Sri Lankans.Significant positive associations were noted between rs886774(LAMB1-gene)and UC(odds ratio(OR)=1.42,P=0.001).UC patients with rs886774 had mild disease(OR=1.66,P<0.001)and remained in remission(OR=1.48,P<0.001).A positive association was noted between rs10045431(IL 12 B gene)and upper gastrointestinal involvement in CD(OR=4.76,P=0.002).CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians.Most SNPs and disease associations reported here have not been described in South Asians.展开更多
It is well know that the nuclei of spermatogenic cells experience one of the most extremely marked chromatin changes known in cells. At the end of spermatogenesis, the histones are removed in many species and the DNA ...It is well know that the nuclei of spermatogenic cells experience one of the most extremely marked chromatin changes known in cells. At the end of spermatogenesis, the histones are removed in many species and the DNA is condensed by the highly positively charged protamines forming highly compact nucleoprotamine complexes.展开更多
Genotoxic effects of industrial effluents werescreened on directly and indirectly exposedpopulations.The exposure is usually chronic tosubtoxic doses of mixed chemicals,forming workplace hazard.Variants of serum prote...Genotoxic effects of industrial effluents werescreened on directly and indirectly exposedpopulations.The exposure is usually chronic tosubtoxic doses of mixed chemicals,forming workplace hazard.Variants of serum proteins andenzymes,used as genetic markers,were展开更多
Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear...Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear divisions and one cytokinesis）. In the majority of known cases the proper segregation of the parental genome into gametes is accom- panied and facilitated by meiotic crossover formation, which contributes to physical association between homologous chromosomes and results in the generation of new combina- tions of alleles in the progeny. This is necessarily a complex and highly regulated process with multiple steps in a tight sequence, including exit from mitosis, DNA double strand break （DSB） formation, homology search, recombinational repair of DSBs and regulation of cohesion between homolo- gous chromosomes. The process of meiosis is astonishingly effective, even in mammals and flowering plants with extremely large genomes, in which this entails the manipula- tion of approximately twelve metres or even more of the replicated diploid DNA, on the order of 10^10 base pairs, with close to base pair accuracy. In plants, meiosis does not pro- duce gametes directly, but progenitors of haploid multicellular structures called gametophytes, which contain haploid cells that differentiate into gametes.展开更多
Since Type 1 diabetes(T1DM)occurs whenβ-cells mass is reduced to less than 20%of the normal level due to autoimmune destruction of cells resulting in the inability to secrete insulin,preservation or replenishment of ...Since Type 1 diabetes(T1DM)occurs whenβ-cells mass is reduced to less than 20%of the normal level due to autoimmune destruction of cells resulting in the inability to secrete insulin,preservation or replenishment of the functionalβ-cells mass has become a major therapeutic focus for this diabetic type treatment.Thus,this 4-week work plan was designed to determine which mesenchymal stem cells(MSCs)type is more appropriate to alleviate pancreatic hazards resulting from diabetes induction;via tracking a comparative study between MSCs derived from adipose tissue(AD-MSCs)and from bone marrow(BM-MSCs)in management of T1DM considering their immunomodulatory,anti-apoptotic and antioxidative roles.Rats were divided randomly into 4 groups;control,STZdiabetic(D),D+AD-MSCs,and D+BM-MSCs groups.Both stem cells types in this study were allogenic.Herein,both oxidative stress and antioxidant markers were evaluated using colorimetric analysis,while inflammatory,immune and apoptotic markers were assessed through flow cytometric analysis.Results showed that diabetic rats treated with either AD-MSCs or BM-MSCs exhibited marked pancreatic antioxidant and anti-inflammatory activities that were able to initiate pancreatic immunomodulation and reducingβ-cells apoptotic death,thus,help to restore their normal insulin secretion and hypoglycemic abilities.However,AD-MSCs injection was shown to be superior as a pancreatic regenerative tool in overcoming diabetes;owing to their marked antioxidant,anti-inflammatory,immunomodulatory,and anti-apoptotic characteristics over BM-MSCs treatment.展开更多
Wheat resistance to Fusarium head blight(FHB)has often been associated with some undesirable agronomic traits.To study the relationship between wheat FHB resistance and agronomic traits,we constructed a linkage map of...Wheat resistance to Fusarium head blight(FHB)has often been associated with some undesirable agronomic traits.To study the relationship between wheat FHB resistance and agronomic traits,we constructed a linkage map of single nucleotide polymorphisms(SNPs)using an F6:8 population from G97252WG97380A.The two hard winter wheat parents showed contrasts in FHB resistance,plant height(HT),heading date(HD),spike length(SL),spike compactness(SC),kernel number per spike(KNS),spikelet number per spike(SNS),thousand-grain weight(TGW)and grain size(length and width).Quantitative trait locus(QTL)mapping identified one major QTL(QFhb.hwwg-2DS)on chromosome arm 2DS for the percentage of symptomatic spikelets(PSS)in the spike,deoxynivalenol(DON)content and Fusarium damaged kernel(FDK).This QTL explained up to 71.8%of the phenotypic variation for the three FHB-related traits and overlapped with the major QTL for HT,HD,SL,KNS,SNS,TGW,and grain size.QTL on chromosome arms 2AL,2DS,3AL and 4BS were significant for the spike and grain traits measured.G97252W contributed FHB resistance and high SNS alleles at QFhb.hwwg-2DS,high KNS alleles at the QTL on 2AL and 2DS,and high TGW and grain size alleles at QTL on 3AL;whereas G97380A contributed high TGW and grain size alleles at the QTL on 2AL and 2DS,respectively,and the high KNS allele at the 4BS QTL.Combining QFhb.hwwg-2DS with positive alleles for spike and grain traits from other chromosomes may simultaneously improve FHB resistance and grain yield in new cultivars.展开更多
Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rarl ...Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rarl （Required for Mla12-specified resistance1）, and Roml （Restoration of Mla-specified resistancel）. The HSP90-SGT1-RAR1 complex appears to function as chaperone in MLA-specified resistance, however, much remains to be discovered regarding the precise signaling underlying plant immunity. Genetic analyses of fast-neutron mutants derived from CI 16151 （Mla6） uncovered a novel locus, designated Rar3 （R_equired for Mla6-specified resitance3）. Rar3 segregates independent of Mla6 and Rarl, and rar3 mutants are susceptible to Blumeria graminis f. sp. hordei （Bgh） isolate 5874 （A VRar）, whereas, wild-type progenitor plants are resistant. Comparative expression analyses of the rar3 mutant vs. its wild-type progenitor were conducted via Barleyl GeneChip and GAIIx paired-end RNA-Seq. Whereas Rarl affects transcription of relatively few genes; Rar3 appears to influence thousands, notably in genes controlling ATP binding, catalytic activity, transcription, and phosphorylation; possibly membrane bound or in the nucleus, eQTL analysis of a segregating doubled haploid population identified over two-thousand genes as being regulated by Mla （q value/FDR=0.00001）, a subset of which are significant in Rar3 interactions. The intersection of datasets derived from mla-loss-of-function mutants, Mla-associated eQTL, and rar3-mediated transcriptome reprogramming are narrowing the focus on essential genes required for Mla-specified immunity.展开更多
There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a...There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.展开更多
Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese exp...Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.展开更多
Characterization of genetically modified organisms through determination of zygosity and transgene integration concerning both copy number and genome site is important for breeding a transgenic line and the use ...Characterization of genetically modified organisms through determination of zygosity and transgene integration concerning both copy number and genome site is important for breeding a transgenic line and the use of these organisms in the purpose for which it was obtained.Southern blot,fluorescence in situ hybridization or mating are demanding and time-consuming techniques traditionally used in the characterization of transgenic organisms and,with the exception of mating,give ambiguous results.With the emergence of the real-time quantitative PCR technology,different applications have been described for the analysis of transgenic organisms by determination of several parameters to transgenic analysis.However,the accuracy in quantitation by this method can be influenced in all steps of analysis.This review focuses on the aspects that influence pre-analytical steps(DNA extraction and DNA quantification methods),quantification strategies and data analysis in quantification of copy number and zygosity in transgenic animals.展开更多
Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper...Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.展开更多
Gallbladder cancer(GBC)is a lethal biliary tract malignancy,which is infrequent in most developed countries,but common in many developing countries in specific geographical regions of the world.Non-specific symptoms l...Gallbladder cancer(GBC)is a lethal biliary tract malignancy,which is infrequent in most developed countries,but common in many developing countries in specific geographical regions of the world.Non-specific symptoms leading to late diagnosis is one of the primary factors contributing to poor prognosis in GBC.An understanding of the complex relationship between molecular genetics and epidemiological variances in the incidence rates of GBC is thus of utmost importance.Present review summarizes recent updates on population-specific dysregulated genetic expressions in the genesis of GBC,highlighting the pattern of ethno-geographic variations and on advances in targeted therapies conducted till date;points out the lacunae that deserve further attention and suggest possible new directions for future clinical trials in GBC.The review calls for the need of genetic screening of each GBC patients and for more extensive clinical trials on targeted therapies to move towards the goal of personalized medicine,bringing about more favourable survival outcomes.展开更多
基金supported by the Key R&D Program of Shandong Province (2024LZGC007, 2024CXPT072, 2022LZGC001)Shandong Provincial Natural Science Foundation (ZR2024YQ069)+1 种基金the National Natural Science Foundation of China (32201863,32272181)the Taishan Scholars Program
文摘Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic architecture underlying CT biosynthesis in wheat grain remains unclear.Here,we studied the deposition and genetic regulation of CT in wheat grains,and found that CT deposited specifically in the testa layer of red-grained wheat as catechin-and epicatechin-formed polymers.Genome-wide association study identified 22 genetic loci affecting CT content,one of which,TaTAN,a single dominant gene controlling CT presence,was mapped to chromosome 3A in a segregation population.Further pan-genome analysis,transcriptome profiling and ethyl methanesulfonate induced mutants sequencing revealed a R2R3-MYB transcription factor,TaMYB10-3A,as the causal gene.Three loss-of-function alleles in TaMYB10-3A caused by large fragment inversion-deletion and insertion were identified which abolish both CT deposition and red pigmentation,demonstrating the pleiotropic effect of TaMYB10-3A on CT presence and grain color.TaMYB10-3A directly trans-activates core flavonoid genes such as chalcone synthase and dihydroflavonol 4-reductase to initiate CT biosynthesis.Our investigation provides a comprehensive understanding of CT presence in wheat grains and lays a solid foundation for manipulating CT metabolites to improve wheat grain end-use quality and nutrition values in wheat.
基金This work was supported by the National Basic Research Program （Nos. 2013CB947900, 2013CB945502 and 2014CB943101） of China （973）, by grants from National Natural Science Foundation of China （No. 31371519） and the Knowledge Innovation Program of the Chinese Academy of Sciences （No. KSCX2-EW-R-07）.
文摘The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.
基金supported by the National Natural Science Foundation of China(81630030,81130024,and 81528008)the National Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme(81461168029)+2 种基金the National Basic Research Development Program of China(2016YFC0904300)the Science and Technology Project of the Health Planning Committee of Sichuan(19PJ090)the National Natural Science Foundation of China for Distinguished Young Scholars(81501159).
文摘The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia.We used prepulse inhibition(PPI)and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls.Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions.Concurrently,we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in firstepisode treatment-naı¨ve schizophrenic patients(n=117)and in age-and sex-matched healthy controls(n=86).We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia.Significant correlations between gray matter volumes(GMVs)in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice.Furthermore,these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients.The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients.Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation,providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia.
文摘Apple replant disease(ARD)is a major limitation to the establishment of economically viable orchards on replant sites due to the buildup and long-term survival of pathogen inoculum.Several soilborne necrotrophic fungi and oomycetes are primarily responsible for ARD,and symptoms range from serious inhibition of growth to the death of young trees.Chemical fumigation has been the primary method used for control of ARD,and manipulating soil microbial ecology to reduce pathogen density and aggressiveness is being investigated.To date,innate resistance of apple rootstocks as a means to control this disease has not been carefully explored,partly due to the complex etiology and the difficulty in phenotyping the disease resistance.Molecular defense responses of plant roots to soilborne necrotrophic pathogens are largely elusive,although considerable progress has been achieved using foliar disease systems.Plant defense responses to necrotrophic pathogens consist of several interacting modules and operate as a network.Upon pathogen detection by plants,cellular signals such as the oscillation of Ca^(2+)concentration,reactive oxygen species(ROS)burst and protein kinase activity,lead to plant hormone biosynthesis and signaling.Jasmonic acid(JA)and ethylene(ET)are known to be fundamental to the induction and regulation of defense mechanisms toward invading necrotrophic pathogens.Complicated hormone crosstalk modulates the fine-tuning of transcriptional reprogramming and metabolic redirection,resulting in production of antimicrobial metabolites,enzyme inhibitors and cell wall refortification to restrict further pathogenesis.Transcriptome profiling of apple roots in response to inoculation with Pythium ultimum demonstrated that there is a high degree of conservation regarding the molecular framework of defense responses compared with those observed with foliar tissues.It is conceivable that the timing and intensity of genotype-specific defense responses may lead to different outcomes between rootstocks in response to invasion by necrotrophic pathogens.Elucidation of host defense mechanisms is critical in developing molecular tools for genomics-assisted breeding of resistant apple rootstocks.Due to their perennial nature,use of resistant rootstocks as a component for disease management might offer a durable and cost-effective benefit to tree performance than the standard practice of soil fumigation for control of ARD.
文摘Although seed oil production and composition are genetically controlled, changes of oil level and oil composition across genotypes and environments such as drought and temperature were observed. The mechanisms of how genotypes interact with environment, affecting oil production and composition, are still not well understood. The objective of this research was to investigate the effect of drought/water stress and temperature on soybean genotypes. Two soybean genotypes of maturity group (MG) II (PI 597411 B and PI 597408) and two of MG VI (Arksoy and PI 437726) were used. A repeated greenhouse experiment to study the effect of water stress and a repeated growth chamber experiment to study the effect of temperature were conducted. The results showed that both water stress and high temperature altered seed oil composition by increasing oleic acid and decreasing linoleic and linolenic acid concentrations. Severe water stress (soil water potential between -150 to -200 kPa) or high temperature (40/33℃, day/night) resulted in higher palmitic acid and lower stearic acid. Genotypes differed in their responses to water stress or temperature. Analyses of seed carbohydrates (glucose, fructose, sucrose, raffinose, and stachyose) showed a significant decline of glucose, fructose, and sucrose and a significant increase of stachyose concentration by water stress and high temperature. Analyses of natural abundance of δ15N and δ13C isotopes showed changes in sources of nitrogen and carbon fixation, possibly affecting nitrogen and carbon metabolism pathways. The research demonstrated that both water stress and high temperature altered oil production and composition, and this could be partially related to limited availability and movement of carbohydrates from leaves to seed. Further research to investigate the enzymes controlling fatty acids conversion and nitrogen and carbon metabolism is needed.
基金funded by the ARS-INHouse fund,USDA-NIFA grant(3200000379-16-182)the National Natural Science Foundation of China(31772371)and AoE grant(AoE/M-403/16).
文摘The Dormancy-associated MADS-box(DAM)gene cluster in peach serves as a key regulatory hub on which the seasonal temperatures act and orchestrate dormancy onset and exit,chilling response and floral bud developmental pace.Yet,how different temperature regimes interact with and regulate the six linked DAM genes remains unclear.Here,we demonstrate that chilling downregulates DAM1 and DAM3–6 in dormant floral buds with distinct patterns and identify DAM4 as the most abundantly expressed one.We reveal multiple epigenetic events,with tri-methyl histone H3 lysine 27(H3K27me3)induced by chilling specifically in DAM1 and DAM5,a 21-nt sRNA in DAM3 and a ncRNA induced in DAM4.Such induction is inversely correlated with downregulation of their cognate DAMs.We also show that the six DAMs were hypermethylated,associating with the production of 24-nt sRNAs.Hence,the chilling-responsive dynamic of the different epigenetic elements and their interactions likely define distinct expression abundance and downregulation pattern of each DAM.We further show that the expression of the five DAMs remains steadily unchanged or continuously downregulated at the ensuing warm temperature after chilling,and this state of regulation correlates with robust increase of sRNA expression,H3K27me3 and CHH methylation,which is particularly pronounced in DAM4.Such robust increase of repressive epigenetic marks may irreversibly reinforce the chillingimposed repression of DAMs to ensure flower-developmental programming free from any residual DAM inhibition.Taken together,we reveal novel information about genetic and epigenetic regulation of the DAM cluster in peach,which will be of fundamental significance in understanding of the regulatory mechanisms underlying chilling requirement and dormancy release,and of practical application for improvement of plasticity of flower time and bud break in fruit trees to adapt changing climates.
文摘Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN.This systematic overview aims to critically evaluate the latest data reported within the scientific literature.The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors.PubMed,Google Scholar,and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years,reporting studies on the main queries addressed in this work.This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers,clarifying and updating the role of genetic factors in SCCHN onset and development.The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN.
基金Supported by National Research Council,Sri Lanka,Grant No.NRC 13-108
文摘AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients.METHODS A case study of histologically confirmed ulcerative colitis(UC)or Crohn's disease(CD)patients with≥1 year disease duration,who were compared to unrelated,gender-matched,healthy individuals as controls,was conducted at four major centers in Sri Lanka.Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants:IL12 B:rs1045431,IL23 R:rs11805303,ARPC2:rs12612347,IRGM:rs13361189,IL26/IL22:rs1558744,CDH1:rs1728785,IL10:rs3024505,FCGR2 A:rs3737240,PTGER4:rs4613763,IL17 REL/PIM3:rs5771069,HNF4 a:rs6017342,STAT3:rs744166,SMURF1:rs7809799,LAMB1:rs886774,HLA-DRB5,DQA1,DRB1,DRA:rs9268853,MST1,UBA7,and APEH:rs9822268.The genotypes of all variants were in Hardy-Weinberg Equilibrium(P>10^(-3)).To account for multiple hypothesis testing,P-values<0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited.Out of the single nucleotide polymorphisms(SNPs)tested,the majority were not associated with IBD in Sri Lankans.Significant positive associations were noted between rs886774(LAMB1-gene)and UC(odds ratio(OR)=1.42,P=0.001).UC patients with rs886774 had mild disease(OR=1.66,P<0.001)and remained in remission(OR=1.48,P<0.001).A positive association was noted between rs10045431(IL 12 B gene)and upper gastrointestinal involvement in CD(OR=4.76,P=0.002).CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians.Most SNPs and disease associations reported here have not been described in South Asians.
文摘It is well know that the nuclei of spermatogenic cells experience one of the most extremely marked chromatin changes known in cells. At the end of spermatogenesis, the histones are removed in many species and the DNA is condensed by the highly positively charged protamines forming highly compact nucleoprotamine complexes.
文摘Genotoxic effects of industrial effluents werescreened on directly and indirectly exposedpopulations.The exposure is usually chronic tosubtoxic doses of mixed chemicals,forming workplace hazard.Variants of serum proteins andenzymes,used as genetic markers,were
文摘Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear divisions and one cytokinesis）. In the majority of known cases the proper segregation of the parental genome into gametes is accom- panied and facilitated by meiotic crossover formation, which contributes to physical association between homologous chromosomes and results in the generation of new combina- tions of alleles in the progeny. This is necessarily a complex and highly regulated process with multiple steps in a tight sequence, including exit from mitosis, DNA double strand break （DSB） formation, homology search, recombinational repair of DSBs and regulation of cohesion between homolo- gous chromosomes. The process of meiosis is astonishingly effective, even in mammals and flowering plants with extremely large genomes, in which this entails the manipula- tion of approximately twelve metres or even more of the replicated diploid DNA, on the order of 10^10 base pairs, with close to base pair accuracy. In plants, meiosis does not pro- duce gametes directly, but progenitors of haploid multicellular structures called gametophytes, which contain haploid cells that differentiate into gametes.
基金This study was funded by Taif University Researchers Supporting Project No.TURSP-2020/222,Taif University,Taif,Saudi Arabia.
文摘Since Type 1 diabetes(T1DM)occurs whenβ-cells mass is reduced to less than 20%of the normal level due to autoimmune destruction of cells resulting in the inability to secrete insulin,preservation or replenishment of the functionalβ-cells mass has become a major therapeutic focus for this diabetic type treatment.Thus,this 4-week work plan was designed to determine which mesenchymal stem cells(MSCs)type is more appropriate to alleviate pancreatic hazards resulting from diabetes induction;via tracking a comparative study between MSCs derived from adipose tissue(AD-MSCs)and from bone marrow(BM-MSCs)in management of T1DM considering their immunomodulatory,anti-apoptotic and antioxidative roles.Rats were divided randomly into 4 groups;control,STZdiabetic(D),D+AD-MSCs,and D+BM-MSCs groups.Both stem cells types in this study were allogenic.Herein,both oxidative stress and antioxidant markers were evaluated using colorimetric analysis,while inflammatory,immune and apoptotic markers were assessed through flow cytometric analysis.Results showed that diabetic rats treated with either AD-MSCs or BM-MSCs exhibited marked pancreatic antioxidant and anti-inflammatory activities that were able to initiate pancreatic immunomodulation and reducingβ-cells apoptotic death,thus,help to restore their normal insulin secretion and hypoglycemic abilities.However,AD-MSCs injection was shown to be superior as a pancreatic regenerative tool in overcoming diabetes;owing to their marked antioxidant,anti-inflammatory,immunomodulatory,and anti-apoptotic characteristics over BM-MSCs treatment.
基金the U.S.Wheat and Barley Scab Initiative and the National Research Initiative Competitive Grants(2022-68013-36439)from the National Institute of Food and Agriculture,U.S.Department of Agriculture(USDA).
文摘Wheat resistance to Fusarium head blight(FHB)has often been associated with some undesirable agronomic traits.To study the relationship between wheat FHB resistance and agronomic traits,we constructed a linkage map of single nucleotide polymorphisms(SNPs)using an F6:8 population from G97252WG97380A.The two hard winter wheat parents showed contrasts in FHB resistance,plant height(HT),heading date(HD),spike length(SL),spike compactness(SC),kernel number per spike(KNS),spikelet number per spike(SNS),thousand-grain weight(TGW)and grain size(length and width).Quantitative trait locus(QTL)mapping identified one major QTL(QFhb.hwwg-2DS)on chromosome arm 2DS for the percentage of symptomatic spikelets(PSS)in the spike,deoxynivalenol(DON)content and Fusarium damaged kernel(FDK).This QTL explained up to 71.8%of the phenotypic variation for the three FHB-related traits and overlapped with the major QTL for HT,HD,SL,KNS,SNS,TGW,and grain size.QTL on chromosome arms 2AL,2DS,3AL and 4BS were significant for the spike and grain traits measured.G97252W contributed FHB resistance and high SNS alleles at QFhb.hwwg-2DS,high KNS alleles at the QTL on 2AL and 2DS,and high TGW and grain size alleles at QTL on 3AL;whereas G97380A contributed high TGW and grain size alleles at the QTL on 2AL and 2DS,respectively,and the high KNS allele at the 4BS QTL.Combining QFhb.hwwg-2DS with positive alleles for spike and grain traits from other chromosomes may simultaneously improve FHB resistance and grain yield in new cultivars.
基金Research supported in part by USA National Science Foundation-Plant Genome Program grant(0922746)
文摘Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rarl （Required for Mla12-specified resistance1）, and Roml （Restoration of Mla-specified resistancel）. The HSP90-SGT1-RAR1 complex appears to function as chaperone in MLA-specified resistance, however, much remains to be discovered regarding the precise signaling underlying plant immunity. Genetic analyses of fast-neutron mutants derived from CI 16151 （Mla6） uncovered a novel locus, designated Rar3 （R_equired for Mla6-specified resitance3）. Rar3 segregates independent of Mla6 and Rarl, and rar3 mutants are susceptible to Blumeria graminis f. sp. hordei （Bgh） isolate 5874 （A VRar）, whereas, wild-type progenitor plants are resistant. Comparative expression analyses of the rar3 mutant vs. its wild-type progenitor were conducted via Barleyl GeneChip and GAIIx paired-end RNA-Seq. Whereas Rarl affects transcription of relatively few genes; Rar3 appears to influence thousands, notably in genes controlling ATP binding, catalytic activity, transcription, and phosphorylation; possibly membrane bound or in the nucleus, eQTL analysis of a segregating doubled haploid population identified over two-thousand genes as being regulated by Mla （q value/FDR=0.00001）, a subset of which are significant in Rar3 interactions. The intersection of datasets derived from mla-loss-of-function mutants, Mla-associated eQTL, and rar3-mediated transcriptome reprogramming are narrowing the focus on essential genes required for Mla-specified immunity.
文摘There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
文摘Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
文摘Characterization of genetically modified organisms through determination of zygosity and transgene integration concerning both copy number and genome site is important for breeding a transgenic line and the use of these organisms in the purpose for which it was obtained.Southern blot,fluorescence in situ hybridization or mating are demanding and time-consuming techniques traditionally used in the characterization of transgenic organisms and,with the exception of mating,give ambiguous results.With the emergence of the real-time quantitative PCR technology,different applications have been described for the analysis of transgenic organisms by determination of several parameters to transgenic analysis.However,the accuracy in quantitation by this method can be influenced in all steps of analysis.This review focuses on the aspects that influence pre-analytical steps(DNA extraction and DNA quantification methods),quantification strategies and data analysis in quantification of copy number and zygosity in transgenic animals.
基金Supported by Department of Biotechnology,Government of India,No.RLS/BT/Re-entry/05/2012.
文摘Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.
文摘Gallbladder cancer(GBC)is a lethal biliary tract malignancy,which is infrequent in most developed countries,but common in many developing countries in specific geographical regions of the world.Non-specific symptoms leading to late diagnosis is one of the primary factors contributing to poor prognosis in GBC.An understanding of the complex relationship between molecular genetics and epidemiological variances in the incidence rates of GBC is thus of utmost importance.Present review summarizes recent updates on population-specific dysregulated genetic expressions in the genesis of GBC,highlighting the pattern of ethno-geographic variations and on advances in targeted therapies conducted till date;points out the lacunae that deserve further attention and suggest possible new directions for future clinical trials in GBC.The review calls for the need of genetic screening of each GBC patients and for more extensive clinical trials on targeted therapies to move towards the goal of personalized medicine,bringing about more favourable survival outcomes.
