Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Metho...Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.展开更多
The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining ro...The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.展开更多
Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult hom...Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.展开更多
Flexible-shelled eggs of the lizards Phrynocephalus przewalskii and P. versicolor were incubated under different thermal and hydric conditions to elicit the effects of incubation environment on hatching success, embry...Flexible-shelled eggs of the lizards Phrynocephalus przewalskii and P. versicolor were incubated under different thermal and hydric conditions to elicit the effects of incubation environment on hatching success, embryonic development and duration as well as hatchling phenotypes. Embryogenesis of the two species was not sensitive to changes in the hydric environment except P. przewalskii incubated in 30°C group. Temperature significantly altered the duration of embryogenesis, with cooler temperatures leading to a longer incubation period. Hatching success was greater at 26 and 30°C than at 34°C. The hatchlings incubated at 26 and 30°C had longer snout-vent length, larger body mass, and better locomotor performance than those incubated at 34°C. Compared to P. przewalskii, P. versicolor had a shorter incubation period and yielded smaller hatchlings, which then had a higher survival rate in cooler and drier habitats. We conclude that an incubation temperature of 30°C would produce the best balance among developmental rate, hatching success, and post-hatching performance. We speculate that the upper temperature limit for incubation of P. versicolor eggs may be slightly higher than 34°C.展开更多
Objective To study the association between the rs7566605 variant of INSIG2 and obesity-related phenotypes in Chinese children and adolescents. Methods The study sample consisted of two independent cohorts of Chinese c...Objective To study the association between the rs7566605 variant of INSIG2 and obesity-related phenotypes in Chinese children and adolescents. Methods The study sample consisted of two independent cohorts of Chinese children and adolescents. Anthropometric indices, lipids, blood pressure, fasting glucose, insulin and percentage of fat mass were determined. PCR with restriction fragment length polymorphism analysis was performed for genotyping the rs7566605 variant. Results In each of the two independent cohorts, no significant association was observed between rs7566605 and obesity under additive, dominant or recessive model. We also did not detect any difference in the genotype frequency between all the obese children and controls. Furthermore, we did not find evidence of an association between body composition indices and metabolic phenotypes in all children. However, the triglyceride level of CC homozygotes was significantly higher than that of GG＋GC genotypes in obese children （P=0.022）. Additionally, we observed a non-significant trend of severe obesity in a post-hoc test. Conclusion INSIG2 rs7566605 variant is not associated Chinese childhood obesity in two independent cohorts. Further study is needed to verify the effect of rs7566605 on triglyceride in obese children.展开更多
Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their r...Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected throuqh Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long- term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies,and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.展开更多
The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Da...The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Daly, 2005; Altshuler et al., 2008）. Together with advanced high-throughput technologies for genotyping and sequencing, GWAS have discovered thousands of susceptibility loci for various traits （Welter et al., 2014）.展开更多
While our understanding of male reproductive strategies is informed by extensive investigations into endocrine mechanisms, the proximate mechanisms by which females compete for mates and adjust reproduction to social ...While our understanding of male reproductive strategies is informed by extensive investigations into endocrine mechanisms, the proximate mechanisms by which females compete for mates and adjust reproduction to social environment remains enigmatic. We set out to uncover endocrine correlates of mate choice, social environment, and reproductive investment in female red-backed fairy-wrens Malurus melanocephalus. In this socially monogamous, yet highly sexually promiscuous species, females experience discrete variation in the phenotype of their mates, which vary in both plumage signals and level of paternal care, and in the composition of their breeding groups, which consist of either the pair alone or with an additional cooperative auxiliary; fe- male investment varies according to these social parameters. We found that androgen, estrogen, and glucorticoid levels varied with reproductive stage, with highest androgen and estrogen concentrations during nest construction and highest corticosterone concentrations during the pre-breeding stage. These stage-dependent patterns did not vary with male phenotype or auxiliary presence, though androgen levels during pre-breeding mate selection were lower in females obtaining red/black mates than those obtaining brown mates. We found no evidence that androgen, estrogen, or corticosterone levels during the fertile period were re- lated to extra-pair young （EPY） frequency. This study demonstrates clear changes in steroid levels with reproductive stage, though it found little support for variation with social environment. We suggest hormonal responsiveness to social factors may be physiologically constrained in ways that are bypassed through exogenous hormone manipulations.展开更多
Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single n...Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms（SNPs） which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies（GWAS） dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.展开更多
Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion ce...Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion cells.Stem cells have been proposed as a potential source of cells for neuronal transplantation.展开更多
Objectives: to evaluate and compare serum adiponectin levels in different phenotypes of polycystic ovary syndrome (PCOS) and to investigate their correlation with endocrine and metabolic parameters. Material and metho...Objectives: to evaluate and compare serum adiponectin levels in different phenotypes of polycystic ovary syndrome (PCOS) and to investigate their correlation with endocrine and metabolic parameters. Material and methods: we studied 5 groups of patients: A (n = 20): H (hyperandrogenism) + O (oligoanovulation) + P (polycystic ovary) [classic phenotype];B (n = 17): H + O [classic phenotype but normal ovaries];C (n = 15): H + P [Ovulatory phenotype];D (n = 17): O + P [Normoandrogenic phenotype];and E (n = 16) control group. Body mass index, waist circumference, waist/hip ratio, blood pressure and hirsutism were evaluated. Serum concentrations of adiponectin, insulin, Creactive protein, SHBG, androgens and lipids were measured. Oral glucose tolerance test was performed. Results: there were no differences between the groups in terms of age and BMI. Total cholesterol, LDL-C and triglyceride levels were higher in phenotype A than in C (P P = 0.03). HOMA-IR, insulin and glucose/insulin ratio were significantly higher in phenotypes A and D vs C and E (P P P < 0.05). Conclusions: adiponectin serum concentrations vary according to the phenotypic expression of PCOS. Our results suggest that adiponectin could be used as a biochemical marker to identify phenotypes at increased metabolic risk.展开更多
BACKGROUND Type 1 diabetes(T1D)incidence varies substantially between countries/territories,with most studies indicating increasing incidence.In Western Pacific region(WPR),reported rates are much lower than European-...BACKGROUND Type 1 diabetes(T1D)incidence varies substantially between countries/territories,with most studies indicating increasing incidence.In Western Pacific region(WPR),reported rates are much lower than European-origin populations.In contrast,there are reports of substantial numbers of young people with type 2 diabetes(T2D).A deeper understanding of T1D and T2D in the WPR may illuminate factors important in pathogenesis of these conditions.Furthermore,with varying resources and funding for diabetes treatment in this region,there is a need to more clearly determine the current burden of disease and also any gaps in knowledge.AIM To compile and summarise published epidemiologic and phenotypic data on childhood diabetes in non-European populations in and from WPR.METHODS Research articles were systematically searched from PubMed(MEDLINE),Embase,Cochrane library,and gray literature.Primary outcome measures were incidence and prevalence,with secondary measures including phenotypic descriptions of diabetes,including diabetes type categorization,presence of diabetic ketoacidosis(DKA)at onset,autoantibody positivity,Cpeptide levels,and human leucocyte antigen phenotype.Extracted data were collected using a customized template.Three hundred and thirty relevant records were identified from 16 countries/territories,with analysis conducted on 265(80.3%)records published from the year 2000.RESULTS T1D incidence ranged from<1-7.3/100000 individuals/year,rates were highest in emigrant/mixed populations and lowest in South-East Asia,with most countries/territories(71.4%)having no data since 1999.Incidence was increasing in all six countries/territories with data(annual increases 0.5%-14.2%,highest in China).Peak age-of-onset was 10-14 years,with a female case excess.Rate of DKA at onset varied from 19.3%-70%.Pancreatic autoantibodies at diagnosis were similar to European-origin populations,with glutamic acid decarboxylase-65 autoantibody frequency of 44.1%-64.5%,insulinoma-associated 2 autoantibody 43.5%-70.7%,and zinc transporter-8 autoantibody frequency 54.3%(one study).Fulminant T1D also occurs.T2D was not uncommon,with incidence in Japan and one Chinese study exceeding T1D rates.Monogenic forms also occurred in a number of countries.CONCLUSION T1D is less common,but generally has a classic phenotype.Some countries/territories have rapidly increasing incidence.T2D is relatively common.Registries and studies are needed to fill many information gaps.展开更多
OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD pati...OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.展开更多
Soybean yield has traditionally been increased through high planting density,but investigating plant height and petiole traits to select for compact architecture,lodging resistance,and high yield varieties is an under...Soybean yield has traditionally been increased through high planting density,but investigating plant height and petiole traits to select for compact architecture,lodging resistance,and high yield varieties is an underexplored option for further improving yield.We compared the relationships between yield-related traits,lodging resistance,and petioleassociated phenotypes in the short petiole germplasm M657 with three control accessions during 2017–2018 in four locations in the Huang–Huai region,China.The results showed that M657 exhibited stable and high tolerance to high planting density and resistance to lodging,especially at the highest density(8×105 plants ha–1).The regression analysis indicated that a shorter petiole length was significantly associated with increased lodging resistance.The yield analysis showed that M657 achieved higher yields under higher densities,especially in the northern part of the Huang–Huai region.Among the varieties,there were markedly different responses to intra-and inter-row spacing designs with respect to both lodging and yield that were related to location and density.Lodging was positively correlated with planting density,plant height,petiole length,and number of effective branches,but negatively correlated with stem diameter,seed number per plant,and seed weight per plant.The yield of soybean was increased by appropriately increasing the planting density on the basis of the current soybean varieties in the Huang–Huai region.This study provides a valuable new germplasm resource for the introgression of compact architecture traits that are amenable to providing a high yield in high density planting systems,and it establishes a high-yield model of soybean in the Huang–Huai region.展开更多
Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,a...Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a展开更多
Adenocarcinoma of the esophagogastric junction （AEG） was proposed as a distinct disease for its rapidly increasing incidence. However, most studies of AEG were based primarily on the results of western patients and ...Adenocarcinoma of the esophagogastric junction （AEG） was proposed as a distinct disease for its rapidly increasing incidence. However, most studies of AEG were based primarily on the results of western patients and the studies on Chinese patients were deficient. Recently, some retrospective studies on AEG patients from our hospital show distinct clinical and pathological features compared with American patients （1-3）. In this editorial, we will focus on the unique phenotypes of Chinese AEG patients based on our studies and other reports.展开更多
Background and Objectives: Asthma is a heterogeneous disease where patient severity can be classified according to various models based on numerous variables. Large collections of well-phenotyped subjects are needed t...Background and Objectives: Asthma is a heterogeneous disease where patient severity can be classified according to various models based on numerous variables. Large collections of well-phenotyped subjects are needed to find distinct clusters of patients for personalized medicine and future genetic studies. The objective of this study is to describe the collection of the Quebec City Case-Control Asthma Cohort and to identify homogeneous subgroups of asthma patients based on clinical characteristics. Methods: This cohort is part of an ongoing project initiated in 2007 to elucidate the genetic basis of asthma. All subjects are randomly recruited at the same site following advertisements. Subjects are unrelated French Canadian white adults 18 years of age or older. Each participant underwent a spirometry, methacholine challenge, and allergy skin-prick tests. Blood was collected for DNA, cell counts and total serum IgE measurements. So far, 982 subjects have been recruited and classified as cases (n = 566) or controls (n = 416). We performed factor and cluster analyses on collected phenotypes from this set to identify subgroups of phenotypically similar asthmatic patients. Results: Factor analysis with 13 variables led to the selection of five factors: lung function, numbers of allergens, blood eosinophil percentage, smoking status and age. K-means cluster analysis on the reduced dataset produced four significantly different groups with the following characteristics: smoking history, low atopy and low lung function, high atopy, and young non-smoking with average atopy. Conclusions: The Quebec City Case-Control Asthma Cohort is a new resource for local and collaborative clinical and genetic research on asthma. This new collection reveals distinct multivariate phenotypes of adult asthma that are likely to be important for future genetic studies and targeted therapies.展开更多
By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of ...By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.展开更多
Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, ...Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81730107 and 81973883)the National Science&Technology Basic Research Project(No.2015FY111700)the Shanghai Pudong New District New Area Project(No.PW2022A-78(WQZ)).
文摘Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.
基金supported by NIH grant AR053293the Van Andel Research Institutesupported by the Van Andel Institute Graduate School
文摘The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.
文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.
基金funded by the National Natural Science Foundation of China(NSFC 31071918)
文摘Flexible-shelled eggs of the lizards Phrynocephalus przewalskii and P. versicolor were incubated under different thermal and hydric conditions to elicit the effects of incubation environment on hatching success, embryonic development and duration as well as hatchling phenotypes. Embryogenesis of the two species was not sensitive to changes in the hydric environment except P. przewalskii incubated in 30°C group. Temperature significantly altered the duration of embryogenesis, with cooler temperatures leading to a longer incubation period. Hatching success was greater at 26 and 30°C than at 34°C. The hatchlings incubated at 26 and 30°C had longer snout-vent length, larger body mass, and better locomotor performance than those incubated at 34°C. Compared to P. przewalskii, P. versicolor had a shorter incubation period and yielded smaller hatchlings, which then had a higher survival rate in cooler and drier habitats. We conclude that an incubation temperature of 30°C would produce the best balance among developmental rate, hatching success, and post-hatching performance. We speculate that the upper temperature limit for incubation of P. versicolor eggs may be slightly higher than 34°C.
基金supported by the grant from National Natural Science Foundation of China (30700668)Specialized Research Fund for the Doctoral Program of Higher Education (20070001811)the Major State Basic Research and Development Program of China (973 program) (2006CB503900).
文摘Objective To study the association between the rs7566605 variant of INSIG2 and obesity-related phenotypes in Chinese children and adolescents. Methods The study sample consisted of two independent cohorts of Chinese children and adolescents. Anthropometric indices, lipids, blood pressure, fasting glucose, insulin and percentage of fat mass were determined. PCR with restriction fragment length polymorphism analysis was performed for genotyping the rs7566605 variant. Results In each of the two independent cohorts, no significant association was observed between rs7566605 and obesity under additive, dominant or recessive model. We also did not detect any difference in the genotype frequency between all the obese children and controls. Furthermore, we did not find evidence of an association between body composition indices and metabolic phenotypes in all children. However, the triglyceride level of CC homozygotes was significantly higher than that of GG＋GC genotypes in obese children （P=0.022）. Additionally, we observed a non-significant trend of severe obesity in a post-hoc test. Conclusion INSIG2 rs7566605 variant is not associated Chinese childhood obesity in two independent cohorts. Further study is needed to verify the effect of rs7566605 on triglyceride in obese children.
文摘Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected throuqh Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long- term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies,and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.
基金supported by the Fundamental Research Funds for the Central Universities (BLX2013026)the National Natural Science Foundation of China (No. 31470675)+2 种基金the National Institutes of Health (K01AA023321)supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University (Contract No. N01-HC-25195)Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278
文摘The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Daly, 2005; Altshuler et al., 2008）. Together with advanced high-throughput technologies for genotyping and sequencing, GWAS have discovered thousands of susceptibility loci for various traits （Welter et al., 2014）.
基金Acknowledgement We sincerely appreciate the commendable field efforts of a large number of field technicians who assisted with data collection during the course of this study, as well as logistical support provided by B. Congdon, T. Daniel, J. Lindsay and D. Westcott. We also thank members of the Schwabl and Webster labs for their valuable input throughout. Thanks also to Becca Sail＇an and Maren Vitousek for the invitation to contribute to this volume. This research was conducted with appropriate permits and permissions from the governments of Queensland and Australia, and material is based upon work supported by the National Science Foundation （USA） through grants to MSW and HS and a graduate traineeship to DGB.
文摘While our understanding of male reproductive strategies is informed by extensive investigations into endocrine mechanisms, the proximate mechanisms by which females compete for mates and adjust reproduction to social environment remains enigmatic. We set out to uncover endocrine correlates of mate choice, social environment, and reproductive investment in female red-backed fairy-wrens Malurus melanocephalus. In this socially monogamous, yet highly sexually promiscuous species, females experience discrete variation in the phenotype of their mates, which vary in both plumage signals and level of paternal care, and in the composition of their breeding groups, which consist of either the pair alone or with an additional cooperative auxiliary; fe- male investment varies according to these social parameters. We found that androgen, estrogen, and glucorticoid levels varied with reproductive stage, with highest androgen and estrogen concentrations during nest construction and highest corticosterone concentrations during the pre-breeding stage. These stage-dependent patterns did not vary with male phenotype or auxiliary presence, though androgen levels during pre-breeding mate selection were lower in females obtaining red/black mates than those obtaining brown mates. We found no evidence that androgen, estrogen, or corticosterone levels during the fertile period were re- lated to extra-pair young （EPY） frequency. This study demonstrates clear changes in steroid levels with reproductive stage, though it found little support for variation with social environment. We suggest hormonal responsiveness to social factors may be physiologically constrained in ways that are bypassed through exogenous hormone manipulations.
基金supported by the National Natural Science Foundation of China (No.81470457 and No.81700297)
文摘Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms（SNPs） which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies（GWAS） dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.
基金supported by grants from the Spanish Ministerio de Cienciay Tecnología(BFU2007-67540)the Junta de Extremadura(PRI06A195,GR10152)
文摘Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion cells.Stem cells have been proposed as a potential source of cells for neuronal transplantation.
文摘Objectives: to evaluate and compare serum adiponectin levels in different phenotypes of polycystic ovary syndrome (PCOS) and to investigate their correlation with endocrine and metabolic parameters. Material and methods: we studied 5 groups of patients: A (n = 20): H (hyperandrogenism) + O (oligoanovulation) + P (polycystic ovary) [classic phenotype];B (n = 17): H + O [classic phenotype but normal ovaries];C (n = 15): H + P [Ovulatory phenotype];D (n = 17): O + P [Normoandrogenic phenotype];and E (n = 16) control group. Body mass index, waist circumference, waist/hip ratio, blood pressure and hirsutism were evaluated. Serum concentrations of adiponectin, insulin, Creactive protein, SHBG, androgens and lipids were measured. Oral glucose tolerance test was performed. Results: there were no differences between the groups in terms of age and BMI. Total cholesterol, LDL-C and triglyceride levels were higher in phenotype A than in C (P P = 0.03). HOMA-IR, insulin and glucose/insulin ratio were significantly higher in phenotypes A and D vs C and E (P P P < 0.05). Conclusions: adiponectin serum concentrations vary according to the phenotypic expression of PCOS. Our results suggest that adiponectin could be used as a biochemical marker to identify phenotypes at increased metabolic risk.
文摘BACKGROUND Type 1 diabetes(T1D)incidence varies substantially between countries/territories,with most studies indicating increasing incidence.In Western Pacific region(WPR),reported rates are much lower than European-origin populations.In contrast,there are reports of substantial numbers of young people with type 2 diabetes(T2D).A deeper understanding of T1D and T2D in the WPR may illuminate factors important in pathogenesis of these conditions.Furthermore,with varying resources and funding for diabetes treatment in this region,there is a need to more clearly determine the current burden of disease and also any gaps in knowledge.AIM To compile and summarise published epidemiologic and phenotypic data on childhood diabetes in non-European populations in and from WPR.METHODS Research articles were systematically searched from PubMed(MEDLINE),Embase,Cochrane library,and gray literature.Primary outcome measures were incidence and prevalence,with secondary measures including phenotypic descriptions of diabetes,including diabetes type categorization,presence of diabetic ketoacidosis(DKA)at onset,autoantibody positivity,Cpeptide levels,and human leucocyte antigen phenotype.Extracted data were collected using a customized template.Three hundred and thirty relevant records were identified from 16 countries/territories,with analysis conducted on 265(80.3%)records published from the year 2000.RESULTS T1D incidence ranged from<1-7.3/100000 individuals/year,rates were highest in emigrant/mixed populations and lowest in South-East Asia,with most countries/territories(71.4%)having no data since 1999.Incidence was increasing in all six countries/territories with data(annual increases 0.5%-14.2%,highest in China).Peak age-of-onset was 10-14 years,with a female case excess.Rate of DKA at onset varied from 19.3%-70%.Pancreatic autoantibodies at diagnosis were similar to European-origin populations,with glutamic acid decarboxylase-65 autoantibody frequency of 44.1%-64.5%,insulinoma-associated 2 autoantibody 43.5%-70.7%,and zinc transporter-8 autoantibody frequency 54.3%(one study).Fulminant T1D also occurs.T2D was not uncommon,with incidence in Japan and one Chinese study exceeding T1D rates.Monogenic forms also occurred in a number of countries.CONCLUSION T1D is less common,but generally has a classic phenotype.Some countries/territories have rapidly increasing incidence.T2D is relatively common.Registries and studies are needed to fill many information gaps.
基金Science and Technology Development Fund of Shanghai Pudong New District (PKJ2017-Y37)Shanghai Natural Science Foundation(18ZR1417900).
文摘OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.
基金funded by the National Natural Science Foundation of China (31271753)the Central Publicinterest Scientific Institution Basal Research Fund, China (S2021ZD02)the Agricultural Science and Technology Innovation Program (ASTIP) of the Chinese Academy of Agricultural Sciences (CAAS-ZDRW202003-1)。
文摘Soybean yield has traditionally been increased through high planting density,but investigating plant height and petiole traits to select for compact architecture,lodging resistance,and high yield varieties is an underexplored option for further improving yield.We compared the relationships between yield-related traits,lodging resistance,and petioleassociated phenotypes in the short petiole germplasm M657 with three control accessions during 2017–2018 in four locations in the Huang–Huai region,China.The results showed that M657 exhibited stable and high tolerance to high planting density and resistance to lodging,especially at the highest density(8×105 plants ha–1).The regression analysis indicated that a shorter petiole length was significantly associated with increased lodging resistance.The yield analysis showed that M657 achieved higher yields under higher densities,especially in the northern part of the Huang–Huai region.Among the varieties,there were markedly different responses to intra-and inter-row spacing designs with respect to both lodging and yield that were related to location and density.Lodging was positively correlated with planting density,plant height,petiole length,and number of effective branches,but negatively correlated with stem diameter,seed number per plant,and seed weight per plant.The yield of soybean was increased by appropriately increasing the planting density on the basis of the current soybean varieties in the Huang–Huai region.This study provides a valuable new germplasm resource for the introgression of compact architecture traits that are amenable to providing a high yield in high density planting systems,and it establishes a high-yield model of soybean in the Huang–Huai region.
基金support from National Heart Lung and Blood Institute Grants P50-HL56985 and R01-HL61794
文摘Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a
文摘Adenocarcinoma of the esophagogastric junction （AEG） was proposed as a distinct disease for its rapidly increasing incidence. However, most studies of AEG were based primarily on the results of western patients and the studies on Chinese patients were deficient. Recently, some retrospective studies on AEG patients from our hospital show distinct clinical and pathological features compared with American patients （1-3）. In this editorial, we will focus on the unique phenotypes of Chinese AEG patients based on our studies and other reports.
文摘Background and Objectives: Asthma is a heterogeneous disease where patient severity can be classified according to various models based on numerous variables. Large collections of well-phenotyped subjects are needed to find distinct clusters of patients for personalized medicine and future genetic studies. The objective of this study is to describe the collection of the Quebec City Case-Control Asthma Cohort and to identify homogeneous subgroups of asthma patients based on clinical characteristics. Methods: This cohort is part of an ongoing project initiated in 2007 to elucidate the genetic basis of asthma. All subjects are randomly recruited at the same site following advertisements. Subjects are unrelated French Canadian white adults 18 years of age or older. Each participant underwent a spirometry, methacholine challenge, and allergy skin-prick tests. Blood was collected for DNA, cell counts and total serum IgE measurements. So far, 982 subjects have been recruited and classified as cases (n = 566) or controls (n = 416). We performed factor and cluster analyses on collected phenotypes from this set to identify subgroups of phenotypically similar asthmatic patients. Results: Factor analysis with 13 variables led to the selection of five factors: lung function, numbers of allergens, blood eosinophil percentage, smoking status and age. K-means cluster analysis on the reduced dataset produced four significantly different groups with the following characteristics: smoking history, low atopy and low lung function, high atopy, and young non-smoking with average atopy. Conclusions: The Quebec City Case-Control Asthma Cohort is a new resource for local and collaborative clinical and genetic research on asthma. This new collection reveals distinct multivariate phenotypes of adult asthma that are likely to be important for future genetic studies and targeted therapies.
文摘By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.
文摘Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.
