Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complem...Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.展开更多
The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epid...As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.展开更多
Canopy photosynthesis,rather than leaf photosynthesis,is highly related to plant biomass and yield formation.Studying canopy photosynthesis and identifying the parameters that control it can help optimize agricultural...Canopy photosynthesis,rather than leaf photosynthesis,is highly related to plant biomass and yield formation.Studying canopy photosynthesis and identifying the parameters that control it can help optimize agricultural management and achieve crop yield potential.Compared with traditional parameters,canopy occupation volume(COV)offers an integrative parameter on canopy architecture related to canopy photosynthetic rates.In this study,we developed a high-throughput method to derive COV for different rice varieties.We first used multi-perspective two-dimensional imaging to reconstruct three-dimensional point clouds of rice plants and developed a suite of pipelines to calculate plant height,leaf number,tiller number,and biomass,with R^(2) values of 91.8%,95.9%,82.3%,and 94.3%,respectively.We further employed point cloud data to reconstruct the surfaces of rice plants and construct a virtual canopy model of the rice population.Light distribution was simulated using a ray-tracing algorithm and canopy photosynthetic rates were simulated via photosynthetic rate-incident light intensity curve fitting.Furthermore,we systematically explored the relationships between canopy phenotypes and photosynthetic rates,and found that COV was the most effective predictor of canopy photosynthesis,achieving an R^(2) value of 92.1%.Adjustment in atmospheric transmittance showed that COV strongly correlated with canopy photosynthesis under different light conditions,with higher accuracy observed under diffuse light.Variations in planting density confirmed that this correlation remained strong at the community level.In summary,this study demonstrates that COV is closely linked to simulated canopy photosynthesis and the developed pipeline can support future agronomic and breeding research.展开更多
Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue...Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.展开更多
Bio-upcycling is an emerging end-of-life strategy for the polymer waste treatment that uses the power of mi-croorganisms to biocatalyticaly convert the pre-treated polymer waste monomers into high-added materials.Poly...Bio-upcycling is an emerging end-of-life strategy for the polymer waste treatment that uses the power of mi-croorganisms to biocatalyticaly convert the pre-treated polymer waste monomers into high-added materials.Poly(ethylene terephthalate)(PET),one of the leading synthetic polyesters in the global polymer market,produced from petrol based feedstock,still has no completely green alternative to meet global demand.Therefore,putting the PET based waste into a circular loop has become one of the major challenges of plastic waste management.In that context,the present study addressed the conversion of PET containing hydrolysates collected after the thermal pretreatment into bacterial nanocellulose(BNC),nowadays one of the most promising biopolymers produced in a sustainable manner.After the optimization of the BNC production cultivated under different conditions in PET hydrolysates,in a static way,the optimal conditions(yield of 3.0 mg/ml)was applied for scaling up.To further open the applicative potential of the BNC produced from PET containing plastic waste,platinum nanoparticles were deposited onto BNC developing new catalyst active in the methanol oxidation re-action.In order to enhance BNC ability to support Pt nanoparticles,it was blended with poly(vinyl alcohol),PVA,producing new PVA/BNC composites,recognized as an improved solid support,rich in hydroxyl groups that serve as an anchor points to Pt deposition.Due to the enrichment of BNC by PVA,it was possible to prepare highly active Pt-based catalyst with only 3 wt% of loaded Pt,which significantly reduce the cost of catalyst production.The cost-effective catalyst was prepared using sodium boron hydride as a reducing agent associated with film casting and fully characterized using FTIR,TGA,XRD,XPS,TEM,SEM-EDX analysis and its potential was confirmed in methanol oxidation reaction.This study explored the circular pathway from PET plastic waste to BNC and further to its potential application in direct methanol fuel cell(DMFC).展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Soybean(Glycine max[L.]Merr.)is an important crop that provides protein and vegetable oil for human consumption.As soybean is a photoperiod-sensitive crop,its cultivation and yield are limited by the photoperiodic con...Soybean(Glycine max[L.]Merr.)is an important crop that provides protein and vegetable oil for human consumption.As soybean is a photoperiod-sensitive crop,its cultivation and yield are limited by the photoperiodic conditions in the field.In contrast to other major crops,soybean has a special plant architecture and a special symbiotic nitrogen fixation system,representing two unique breeding directions.Thus,flowering time,plant architecture,and symbiotic nitrogen fixation are three critical or unique yielddetermining factors.This review summarizes the progress made in our understanding of these three critical yield-determining factors in soybean.Meanwhile,we propose potential research directions to increase soybean production,discuss the application of genomics and genomic-assisted breeding,and explore research directions to address future challenges,particularly those posed by global climate changes.展开更多
Global warming threatens food security.Rice(Oryza sativa L.),a vital food crop,is vulnerable to heat stress,especially at the reproductive stage.Here we summarize putative mechanisms of high-temperature perception(via...Global warming threatens food security.Rice(Oryza sativa L.),a vital food crop,is vulnerable to heat stress,especially at the reproductive stage.Here we summarize putative mechanisms of high-temperature perception(via RNA secondary structure,the phyB gene,and phase separation)and response(membrane fluidity,heat shock factors,heat shock proteins,and ROS(reactive oxygen species)scavenging)in plants.We describe how rice responds to heat stress at different cell-component levels(membrane,endoplasmic reticulum,chloroplasts,and mitochondria)and functional levels(denatured protein elimination,ROS scavenging,stabilization of DNA and RNA,translation,and metabolic flux changes).We list temperature-sensitive genetic male sterility loci available for use in rice hybrid breeding and explain the regulatory mechanisms associated with some of them.Breeding thermotolerant rice species without yield penalties via natural alleles mining and transgenic editing should be the focus of future work.展开更多
Spermatogenesis involves extremely marked cellular, genetic and chromatin changes resulting in the generation of the highly specialized sperm cell. Proteomics allows the identification of the proteins that compose the...Spermatogenesis involves extremely marked cellular, genetic and chromatin changes resulting in the generation of the highly specialized sperm cell. Proteomics allows the identification of the proteins that compose the spermatogenic cells and the study of their function. The recent developments in mass spectrometry （MS） have markedly increased the throughput to identify and to study the sperm proteins. Catalogs of thousands of testis and spermatozoan proteins in human and different model species are becoming available, setting up the basis for subsequent research, diagnostic applications and possibly the future development of specific treatments. The present review intends to summarize the key genetic and chromatin changes at the different stages of spermatogenesis and in the mature sperm cell and to comment on the presently available proteomic studies.展开更多
Composite colorectal carcinomas are rare. There are amodest number of cases in the medical literature,with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There areto our k...Composite colorectal carcinomas are rare. There are amodest number of cases in the medical literature,with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There areto our knowledge no reports of composite carcinomamolecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau-casian male to investigate the presence and prognos-tic significance of molecular alterations in rare coloniccarcinoma subtypes. Formalin-fixed paraffin-embedded(FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol,and immuno-stained with cytokeratin(CK) 7,CK20,CDX2,AE1/AE3,chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performed according to lab-developed methods,followed by capil-lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squamous cells. Positive nuclear CDX2 expression confirme dintestinal derivation. CK7 and CK20 were negative.Neuroendocrine cells stained positively for synaptophysin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar immunohistochemical profile. Molecular analysis revealeda G13D KRAS mutation. BRAF mutational testing wasnegative and microsatellite instability was not detected.The patient had rapid disease progression on chemotherapy and died 60 d after presentation. Although theG13D KRAS mutation normally predicts an intermed iateoutcome,the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.展开更多
AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC ...AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor.展开更多
Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of adv...Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.展开更多
AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypo...AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypolactasia and filled in a structured questionnaire concerning milk consumption and gastrointestinal problems. RESULTS: The C/C-13910 genotype of adult-type hypolactasia was present in 18% of the study population. The prevalence of the C/C-13910 genotype was higher among subjects who were undergoing investigations because of abdominal symptoms (24%, P < 0.05). Those with the C/C-13910 genotype drank less milk than subjects with either the C/T-13910 or the T/T-13910 genotype of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C-13910 genotype had experienced more gastrointestinal symptoms (84%) during the preceding three-month period than those with the C/T-13910 (79%, P < 0.05) or the T/T-13910 genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with the C/C-13910 genotype consumed milk and reported no symptoms from it.CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C-13910 genotype of adult-type hypolactasia than in those with genotypes of lactase persistence.展开更多
The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and...The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.展开更多
The timing of the onset and release of dormancy impacts the survival,productivity and spatial distribution of temperate horticultural and forestry perennials and is mediated by at least three main regulatory programs ...The timing of the onset and release of dormancy impacts the survival,productivity and spatial distribution of temperate horticultural and forestry perennials and is mediated by at least three main regulatory programs involving signal perception and processing by phytochromes(PHYs)and PHY-interacting transcription factors(PIFs).PIF4 functions as a key regulator of plant growth in response to both external and internal signals.In poplar,the expression of PIF4 and PIF3-LIKE1 is upregulated in response to short days,while PHYA and PHYB are not regulated at the transcriptional level.Integration of light and environmental signals is achieved by gating the expression and transcriptional activity of PIF4.During this annual cycle,auxin promotes the degradation of Aux/IAA transcriptional repressors through the SKP–Cullin-F–boxTIR1 complex,relieving the repression of auxin-responsive genes by allowing auxin response factors(ARFs)to activate the transcription of auxin-responsive genes involved in growth responses.Analyses of transcriptome changes during dormancy transitions have identified MADS-box transcription factors associated with endodormancy induction.Previous studies show that poplar dormancy-associated MADS-box(DAM)genes PtMADS7 and PtMADS21 are differentially regulated during the growth-dormancy cycle.Endodormancy may be regulated by internal factors,which are specifically localized in buds.PtMADS7/PtMADS21 may function as an internal regulator in poplar.The control of flowering time shares certain regulatory hierarchies with control of the dormancy/growth cycle.However,the particularities of different stages of the dormancy/growth cycle warrant comprehensive approaches to identify the causative genes for the entire cycle.A growing body of knowledge also indicates epigenetic regulation plays a role in these processes in perennial horticultural and forestry plants.The increased knowledge contributes to better understanding of the dormancy process and consequently to precise manipulation of dormancy-related horticultural traits,such as flowering time.展开更多
The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better...The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better understand the etiology of psychiatric disorders.One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation.While some epigenetic modifications(such as DNA methylation)are well known and studied,the roles of others have been investigated much less.DNA hydroxymethylation is a rarely studied epigenetic modification,which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity.In contrast to DNA methylation,DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression.Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders,the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment,which both influence the development of psychiatric disorders,and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.展开更多
The common carp (Cyprinus carpio) has a large variety of strains. The more popular are the koi (Japanese ornamental carp), which are still bred today to generate creative colors and patterns, giving rise to multiple p...The common carp (Cyprinus carpio) has a large variety of strains. The more popular are the koi (Japanese ornamental carp), which are still bred today to generate creative colors and patterns, giving rise to multiple phenotypes. Since koi are in great demand, there is a challenge to determine the genetics defining their quality. Two methods: 1) direct sequencing of five candidate gene regions, i.e., mitochondrial (cytochrome b, 12S gene and the D-loop) and nuclear (red sensitive opsin and Rag-1) loci, to detect single nucleotide polymorphisms (SNP)s and 2) random amplification of polymorphic DNA (RAPD), were used to differentiate among four koi strains (Kohaku, Sanke, Ghost and Ohgon) and the common carp. Novel SNPs, distinguishing between koi and the common carp, were revealed in cytochrome b, the D-loop and in the red sensitive opsin;one was a missense mutation in cytochrome b at position 15860, in which threonine in the common carp became alanine in all koi strains examined. The Kohaku strain was found to have two alleles in the mitochondrial fragments, forming two different haplotypes (subpo-pulations). These novel SNPs distinguished between koi strains and the common carp, and the RAPD method enabled further differentiation among the four koi strains.展开更多
Trees convert and store the majority of their photosynthetic products in wood which is an essential renewable resource much in demand by human society.Formation of wood follows a process of consecutive cell developmen...Trees convert and store the majority of their photosynthetic products in wood which is an essential renewable resource much in demand by human society.Formation of wood follows a process of consecutive cell developmental stages,from vascular cambium proliferation,cell expansion and differentiation,secondary cell wall deposition to programmed cell death,which is controlled by the functionality of complex molecular networks.What are the molecular networks involved in wood formation?How do the molecular networks act in a way to generate wood tissue during tree growth?What are the regulatory modules that lead to the formation of various wood characteristics?The answers to these questions are fundamental to understanding how trees grow,as well as how we can genetically engineer trees with desired properties of wood for human needs.In recent years,a great deal of interest has been invested in the elucidation of wood formation at the molecular level.This review summarizes the current state of understanding of the molecular process that guides wood formation in trees.展开更多
AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ per...AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.展开更多
基金Supported by Slovenian Research and Innovation Agency Program,No.P1-0390 and No.N3-0349Slovenian Research and Innovation Agency Program,Young Researcher Grant(toŠmon J).
文摘Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
基金supported by grants from the Applied Basic Research Foundation of Yunnan Province(202301AT070095)the Candidate Talents Training Fund of Yunnan Province(H-2024069)。
文摘As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.
基金supported by the National Natural Science Foundation of China(Grant Nos.32201654 and U22A20464)National Key Research and Development Program from the Ministry of Science and Technology of China(Grant No.2020YFA0907600)the 2115 Talent Development Program of China Agricultural University.
文摘Canopy photosynthesis,rather than leaf photosynthesis,is highly related to plant biomass and yield formation.Studying canopy photosynthesis and identifying the parameters that control it can help optimize agricultural management and achieve crop yield potential.Compared with traditional parameters,canopy occupation volume(COV)offers an integrative parameter on canopy architecture related to canopy photosynthetic rates.In this study,we developed a high-throughput method to derive COV for different rice varieties.We first used multi-perspective two-dimensional imaging to reconstruct three-dimensional point clouds of rice plants and developed a suite of pipelines to calculate plant height,leaf number,tiller number,and biomass,with R^(2) values of 91.8%,95.9%,82.3%,and 94.3%,respectively.We further employed point cloud data to reconstruct the surfaces of rice plants and construct a virtual canopy model of the rice population.Light distribution was simulated using a ray-tracing algorithm and canopy photosynthetic rates were simulated via photosynthetic rate-incident light intensity curve fitting.Furthermore,we systematically explored the relationships between canopy phenotypes and photosynthetic rates,and found that COV was the most effective predictor of canopy photosynthesis,achieving an R^(2) value of 92.1%.Adjustment in atmospheric transmittance showed that COV strongly correlated with canopy photosynthesis under different light conditions,with higher accuracy observed under diffuse light.Variations in planting density confirmed that this correlation remained strong at the community level.In summary,this study demonstrates that COV is closely linked to simulated canopy photosynthesis and the developed pipeline can support future agronomic and breeding research.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)[(2024)648]the Program of China National Tobacco Corporation(110202101032(JY-09),110202201003(JY-03))+2 种基金the Program of Guizhou Branch of China National Tobacco Corporation(2023XM02,2022XM05 and 2024XM01)the Qiankehe Platform Project(ZSYS[2025]028)the Program of China National Tobacco Corporation(110202102034).
文摘Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.
基金financially supported from the European Union’s Horizon Europe EIC Pathfinder programme under agreement No 101046758(EcoPlastiC)by the Ministry of Science,Innovation and Technological Development of the Republic of Serbia(Agreement No.451-03-66/2024-03/200042 and No.451-03-66/2024-03/2000026)by the Science Fund of the Republic of Serbia under the grant No 7739802.
文摘Bio-upcycling is an emerging end-of-life strategy for the polymer waste treatment that uses the power of mi-croorganisms to biocatalyticaly convert the pre-treated polymer waste monomers into high-added materials.Poly(ethylene terephthalate)(PET),one of the leading synthetic polyesters in the global polymer market,produced from petrol based feedstock,still has no completely green alternative to meet global demand.Therefore,putting the PET based waste into a circular loop has become one of the major challenges of plastic waste management.In that context,the present study addressed the conversion of PET containing hydrolysates collected after the thermal pretreatment into bacterial nanocellulose(BNC),nowadays one of the most promising biopolymers produced in a sustainable manner.After the optimization of the BNC production cultivated under different conditions in PET hydrolysates,in a static way,the optimal conditions(yield of 3.0 mg/ml)was applied for scaling up.To further open the applicative potential of the BNC produced from PET containing plastic waste,platinum nanoparticles were deposited onto BNC developing new catalyst active in the methanol oxidation re-action.In order to enhance BNC ability to support Pt nanoparticles,it was blended with poly(vinyl alcohol),PVA,producing new PVA/BNC composites,recognized as an improved solid support,rich in hydroxyl groups that serve as an anchor points to Pt deposition.Due to the enrichment of BNC by PVA,it was possible to prepare highly active Pt-based catalyst with only 3 wt% of loaded Pt,which significantly reduce the cost of catalyst production.The cost-effective catalyst was prepared using sodium boron hydride as a reducing agent associated with film casting and fully characterized using FTIR,TGA,XRD,XPS,TEM,SEM-EDX analysis and its potential was confirmed in methanol oxidation reaction.This study explored the circular pathway from PET plastic waste to BNC and further to its potential application in direct methanol fuel cell(DMFC).
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金supported by the National Natural Science Foundation of China(32090064 and 32001503)the National Key Research and Development Program of China(2022YFD1201400)。
文摘Soybean(Glycine max[L.]Merr.)is an important crop that provides protein and vegetable oil for human consumption.As soybean is a photoperiod-sensitive crop,its cultivation and yield are limited by the photoperiodic conditions in the field.In contrast to other major crops,soybean has a special plant architecture and a special symbiotic nitrogen fixation system,representing two unique breeding directions.Thus,flowering time,plant architecture,and symbiotic nitrogen fixation are three critical or unique yielddetermining factors.This review summarizes the progress made in our understanding of these three critical yield-determining factors in soybean.Meanwhile,we propose potential research directions to increase soybean production,discuss the application of genomics and genomic-assisted breeding,and explore research directions to address future challenges,particularly those posed by global climate changes.
基金supported by the National Natural Science Foundation of China(31630052,31788103)Chinese Academy of Sciences(XDB27010104,QYZDYSSW-SMC023,159231KYSB20200008)+1 种基金the National Key Research and Development Program of China(2016YFD0100604)the Shanghai Science and Technology Development(18JC1415000)。
文摘Global warming threatens food security.Rice(Oryza sativa L.),a vital food crop,is vulnerable to heat stress,especially at the reproductive stage.Here we summarize putative mechanisms of high-temperature perception(via RNA secondary structure,the phyB gene,and phase separation)and response(membrane fluidity,heat shock factors,heat shock proteins,and ROS(reactive oxygen species)scavenging)in plants.We describe how rice responds to heat stress at different cell-component levels(membrane,endoplasmic reticulum,chloroplasts,and mitochondria)and functional levels(denatured protein elimination,ROS scavenging,stabilization of DNA and RNA,translation,and metabolic flux changes).We list temperature-sensitive genetic male sterility loci available for use in rice hybrid breeding and explain the regulatory mechanisms associated with some of them.Breeding thermotolerant rice species without yield penalties via natural alleles mining and transgenic editing should be the focus of future work.
文摘Spermatogenesis involves extremely marked cellular, genetic and chromatin changes resulting in the generation of the highly specialized sperm cell. Proteomics allows the identification of the proteins that compose the spermatogenic cells and the study of their function. The recent developments in mass spectrometry （MS） have markedly increased the throughput to identify and to study the sperm proteins. Catalogs of thousands of testis and spermatozoan proteins in human and different model species are becoming available, setting up the basis for subsequent research, diagnostic applications and possibly the future development of specific treatments. The present review intends to summarize the key genetic and chromatin changes at the different stages of spermatogenesis and in the mature sperm cell and to comment on the presently available proteomic studies.
基金Supported by Intradepartmental funds through Vanderbilt University Medical Center Department of Pathology for residentcareer development
文摘Composite colorectal carcinomas are rare. There are amodest number of cases in the medical literature,with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There areto our knowledge no reports of composite carcinomamolecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau-casian male to investigate the presence and prognos-tic significance of molecular alterations in rare coloniccarcinoma subtypes. Formalin-fixed paraffin-embedded(FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol,and immuno-stained with cytokeratin(CK) 7,CK20,CDX2,AE1/AE3,chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performed according to lab-developed methods,followed by capil-lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squamous cells. Positive nuclear CDX2 expression confirme dintestinal derivation. CK7 and CK20 were negative.Neuroendocrine cells stained positively for synaptophysin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar immunohistochemical profile. Molecular analysis revealeda G13D KRAS mutation. BRAF mutational testing wasnegative and microsatellite instability was not detected.The patient had rapid disease progression on chemotherapy and died 60 d after presentation. Although theG13D KRAS mutation normally predicts an intermed iateoutcome,the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.
基金Supported by The Instituto de Salud Carlos Ⅲ, Ministerio de Sanidad y Consumo (FIS01-04, project P047-04)
文摘AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor.
基金Supported by IU Simon Comprehensive Cancer Center grant,No.5P30CA082709-24.
文摘Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.
基金the Sigrid Jusélius Foundation, Helsinki, Finlandthe Foundation for Nutrition Research, Helsinki, Finland+3 种基金the Research Foundation of Alfred Kordelin, Helsinki, FinlandHelsinki University Hospital Research Funding, Helsinki, Finlandthe Foundation for Promoting Occupational Medicine in Finland,Helsinki,Finlandthe Academy of Finland
文摘AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypolactasia and filled in a structured questionnaire concerning milk consumption and gastrointestinal problems. RESULTS: The C/C-13910 genotype of adult-type hypolactasia was present in 18% of the study population. The prevalence of the C/C-13910 genotype was higher among subjects who were undergoing investigations because of abdominal symptoms (24%, P < 0.05). Those with the C/C-13910 genotype drank less milk than subjects with either the C/T-13910 or the T/T-13910 genotype of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C-13910 genotype had experienced more gastrointestinal symptoms (84%) during the preceding three-month period than those with the C/T-13910 (79%, P < 0.05) or the T/T-13910 genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with the C/C-13910 genotype consumed milk and reported no symptoms from it.CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C-13910 genotype of adult-type hypolactasia than in those with genotypes of lactase persistence.
文摘The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.
文摘The timing of the onset and release of dormancy impacts the survival,productivity and spatial distribution of temperate horticultural and forestry perennials and is mediated by at least three main regulatory programs involving signal perception and processing by phytochromes(PHYs)and PHY-interacting transcription factors(PIFs).PIF4 functions as a key regulator of plant growth in response to both external and internal signals.In poplar,the expression of PIF4 and PIF3-LIKE1 is upregulated in response to short days,while PHYA and PHYB are not regulated at the transcriptional level.Integration of light and environmental signals is achieved by gating the expression and transcriptional activity of PIF4.During this annual cycle,auxin promotes the degradation of Aux/IAA transcriptional repressors through the SKP–Cullin-F–boxTIR1 complex,relieving the repression of auxin-responsive genes by allowing auxin response factors(ARFs)to activate the transcription of auxin-responsive genes involved in growth responses.Analyses of transcriptome changes during dormancy transitions have identified MADS-box transcription factors associated with endodormancy induction.Previous studies show that poplar dormancy-associated MADS-box(DAM)genes PtMADS7 and PtMADS21 are differentially regulated during the growth-dormancy cycle.Endodormancy may be regulated by internal factors,which are specifically localized in buds.PtMADS7/PtMADS21 may function as an internal regulator in poplar.The control of flowering time shares certain regulatory hierarchies with control of the dormancy/growth cycle.However,the particularities of different stages of the dormancy/growth cycle warrant comprehensive approaches to identify the causative genes for the entire cycle.A growing body of knowledge also indicates epigenetic regulation plays a role in these processes in perennial horticultural and forestry plants.The increased knowledge contributes to better understanding of the dormancy process and consequently to precise manipulation of dormancy-related horticultural traits,such as flowering time.
基金Supported by Slovenian Research Agency,Young Researcher Grant toŠalamon Arčan I,No.P1-0390,J3-4533,Z3-2653.
文摘The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better understand the etiology of psychiatric disorders.One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation.While some epigenetic modifications(such as DNA methylation)are well known and studied,the roles of others have been investigated much less.DNA hydroxymethylation is a rarely studied epigenetic modification,which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity.In contrast to DNA methylation,DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression.Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders,the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment,which both influence the development of psychiatric disorders,and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.
文摘The common carp (Cyprinus carpio) has a large variety of strains. The more popular are the koi (Japanese ornamental carp), which are still bred today to generate creative colors and patterns, giving rise to multiple phenotypes. Since koi are in great demand, there is a challenge to determine the genetics defining their quality. Two methods: 1) direct sequencing of five candidate gene regions, i.e., mitochondrial (cytochrome b, 12S gene and the D-loop) and nuclear (red sensitive opsin and Rag-1) loci, to detect single nucleotide polymorphisms (SNP)s and 2) random amplification of polymorphic DNA (RAPD), were used to differentiate among four koi strains (Kohaku, Sanke, Ghost and Ohgon) and the common carp. Novel SNPs, distinguishing between koi and the common carp, were revealed in cytochrome b, the D-loop and in the red sensitive opsin;one was a missense mutation in cytochrome b at position 15860, in which threonine in the common carp became alanine in all koi strains examined. The Kohaku strain was found to have two alleles in the mitochondrial fragments, forming two different haplotypes (subpo-pulations). These novel SNPs distinguished between koi strains and the common carp, and the RAPD method enabled further differentiation among the four koi strains.
基金supported by the National Nature Science Foundation of China(32130072,31630014)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB27020104).
文摘Trees convert and store the majority of their photosynthetic products in wood which is an essential renewable resource much in demand by human society.Formation of wood follows a process of consecutive cell developmental stages,from vascular cambium proliferation,cell expansion and differentiation,secondary cell wall deposition to programmed cell death,which is controlled by the functionality of complex molecular networks.What are the molecular networks involved in wood formation?How do the molecular networks act in a way to generate wood tissue during tree growth?What are the regulatory modules that lead to the formation of various wood characteristics?The answers to these questions are fundamental to understanding how trees grow,as well as how we can genetically engineer trees with desired properties of wood for human needs.In recent years,a great deal of interest has been invested in the elucidation of wood formation at the molecular level.This review summarizes the current state of understanding of the molecular process that guides wood formation in trees.
基金Supported by The Sigrid Juselius Foundation, Helsinki, Finland The Helsinki University Hospital Research Funding, Helsinki, Finland The Helsinki University Science Foundation, Helsinki, Finland and The Foundation of Nutrition Research, Helsinki, Finland
文摘AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.
