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Population-standardized genetic risk score： the SNP-based method of choice for inherited risk assessment of prostate cancer

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Asian Journal of Andrology 2016年第4期18卷 520-524页

作者： Carly A Conran Rong Na Haitao Chen Deke Jiang Xiaoling Lin S Lilly Zheng charles b brendler Jianfeng Xu NorthShore University HealthSystem Program for Personalized Cancer Care 1001 University Place Evanston IL 60201 USA Fudan Institute of Urology Huashan Hospital Fudan University 12 Mid-Wulumuqi Road Shanghai 200040 P.R. China Center for Genomic Translational Medicine and Prevention School of Public Health Fudan University 138 Yixueyuan Road Shanghai 200032 RR. China.

Several different approaches are available to clinicians for determining prostate cancer （PCa） risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms （SNPs） has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men （n = 1654） enrolled in a prospective study of PCa development. Genotypes of 59 PCa risk-associated SNPs were available in this cohort. Three methods of calculating SNP-based genetic risk scores （GRSs） were used for the evaluation of individual disease risk such as risk allele count （GRS-RAC）, weighted risk allele count （GRS-wRAC）, and population-standardized genetic risk score （GRS-PS）. Mean GRSs were calculated, and performances were compared using area under the receiver operating characteristic curve （AUC） and positive predictive value （PPV）. All SNP-based methods were found to be independently associated with PCa （all P 〈 0.05; hence their clinical validity）. The mean GRSs in men with or without PCa using GRS-RAC were 55.15 and 53.46, respectively, using GRS-wRAC were 7.42 and 6.97, respectively, and using GRS-PS were 1.12 and 0.84, respectively （all P 〈 0.05 for differences between patients with or without PCa）. All three SNP-based methods performed similarly in discriminating PCa from non-PCa based on AUC and in predicting PCa risk based on PPV （all P 〉 0.05 for comparisons between the three methods）, and all three SNP-based methods had a significantly higher AUC than family history （all P 〈 0.05）. Results from this study suggest that while the three most commonly used SNP-based methods performed similarly in discriminating PCa from non-PCa at the population level, GRS-PS is the method of choice for risk assessment at the individual level because its value （where 1.0 represents average population risk） can be easily interpreted regardless of

关键词： genetic risk score prostate cancer single nucleotide polymorphisms

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： charles H.Nelson Udai b.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases

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Asian Journal of Andrology 2016年第4期18卷 525-529页

作者： Rong Na Dingwei Ye Jun Qi Fang Liu Xiaoling Lin brian T Helfand charles b brendler Carly Conran Jian Gong Yishuo Wu Xu Gao Yaqing Chen S Lilly Zheng Zengnan Mo Qiang Ding Yinghao Sun Jianfeng Xu Department of Urology Huashan Hospital Fudan University Shanghai China Fudan Institute of Urology Huashan Hospital Fudan University Shanghai China Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA Health Communication Institute School of Public Health Fudan University Shanghai China Department of Urology Shanghai Cancer Center Fudan University Shanghai China Department of Urology Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Division of Urology NorthShore University HealthSystem Evanston Illinois USA Department of Urology Shanghai Changhai Hospital The Second Military Medical University Shanghai China Department of Medical Ultrasonic Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Center for Genomic and Personalized Medicine Guangxi Medical University Nanning China

Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.

关键词： Chinese genetic risk score genome-wide association study prostate cancer single nucleotide polymorphism

Long-term monitoring of cycles in Clethrionomys rutilus in the Yukon boreal forest

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Integrative Zoology 2024年第1期19卷 27-36页

作者： charles J.KREbS Alice J.KENNEY b.Scott GILbERT Rudy bOONSTRA Department of Zoology University of British ColumbiaVancouverBritish ColumbiaCanada Renewable Resources Management Program Yukon UniversityWhitehorseYukonCanada Department of biological Sciences University of Toronto ScarboroughTorontoOntarioCanada

baseline studies of small rodent populations in undisturbed ecosystems are *** report here 50 years of mon-itoring and experimentation in Yukon of a dominant rodent species in the North American boreal forest,the red-backed vole Clethrionomys *** voles breed in summer,weigh 20–25 g,and reach a maximum density of 20 to 25 per *** populations have shown consistent 3–4-year cycles for the last 50 years with the only change being that peak densities averaged 8/ha until 2000 and 18/ha since that *** the last 25 years,we have measured food resources,predator numbers,and winter weather,and for 1-year social interactions,to estimate their contribution to changes in the rate of summer increase and the rate of overwinter *** these potential limiting factors could contribute to changes in density,and we measured their relative contributions statistically with multiple *** rate of winter decline in density was related to both food supply and winter *** rate of summer increase was related to summer berry crops and white spruce cone *** measure of predator numbers was related to winter or summer changes in vole *** was a large signal of climate change effects in these *** is no density dependence in summer population growth and only a weak one in winter population *** of our results provide a clear understanding of what generates 3–4-year cycles in these voles,and the major missing piece may be an understanding of social interactions at high density.

关键词： boreal forest climate change density dependence population cycles predation winter severity

Synchronization and firing mode transition of two neurons in a bilateral auditory system driven by a high–low frequency signal

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Chinese Physics b 2024年第5期33卷 722-735页

作者： charles Omotomide Apata 唐浥瑞周祎凡蒋龙裴启明 School of Physics and Optoelectronic Engineering Yangtze UniversityJingzhou 434023China

The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron *** piezoelectric sensing neurons are coupled by a parallel circuit consisting of a Josephson junction and a linear resistor,and a binaural auditory system is *** the non-singleness of external sound sources,the high–low frequency signal is used as the input signal to study the firing mode transition and synchronization of this *** is found that the angular frequency of the high–low frequency signal is a key factor in determining whether the dynamic behaviors of two coupled neurons are *** they are in synchronization at a specific angular frequency,the changes in physical parameters of the input signal and the coupling strength between them will not destroy their *** addition,the firing mode of two coupled auditory neurons in synchronization is affected by the characteristic parameters of the high–low frequency signal rather than the coupling *** asynchronous dynamic behavior and variations in firing modes will harm the auditory *** findings could help determine the causes of hearing loss and devise functional assistive devices for patients.

关键词： piezoelectric ceramic Josephson junction auditory neuron synchronization

bulk geochemistry,Rb-Sr,Sm-Nd,and stable O-H isotope systematics of the Metzimevin high-grade iron ore deposit,Mbalam iron ore district,southern Cameroon

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Acta Geochimica 2024年第4期43卷 677-706页

作者： Samndong Cyril Tufoin Cheo Emmanuel Suh Tabod charles Tabod George Lemewihbwen Ngiamte Department of Geology Mining and Environmental ScienceThe University of BamendaB.P.39BambiliNorth West RegionCameroon Economic Geology Unit Department of GeologyUniversity of BueaP.O.63BueaSouth West RegionCameroon Department of Physics Faculty of ScienceThe University of BamendaB.P.39BambiliNorth West RegionCameroon Department of Geology Pan-African University Life and Earth Sciences Institute(PAULESI)University of IbadanIbadanNigeria

bulk geochemistry,Sr,Nd,and O-H isotope systematics are reported for the first time on banded iron formation(bIF)-hosted high-grade iron ore at the northwestern segment of Congo Craton(CC).Located in Mbalam iron ore district,Southern Cameroon,Metzimevin iron ore deposit is a hematite-magnetite bIF system,dominated by SiO_(2)+Fe_(2)O_(3)(97.1 to 99.84 wt%),with low concentrations of clastic elements e.g.,Al_(2)O_(3),TiO_(2),and HFSE,depicting a nearly pure chemical *** REE+Y signature of the iron deposit displays strong positive Eu anomaly,strong negative Ce anomaly,and chondritic to superchondritic Y/Ho ratios,suggestive of formation by mixed seawater-high temperature hydrothermal fluids in oxidising ***^(87)Sr/^(86)Sr ratios of the bIF are higher than the maximum^(87)Sr/^(86)Sr evolution curves for all Archean reservoirs(bulk silicate earth,Archean crust and Archean seawater),indicating involvement of continentally-derived components during bIF formation and ***Ɛ_(Nd)(t)(+2.26 to+3.77)and Nd model age indicate that chemical constituents for the bIF were derived from undifferentiated crustal source,between 3.002 and 2.88 *** variable and diverse O and H isotope data(−1.9‰to 17.3‰and−57‰to 136‰respectively)indicate that the Metzimevin iron ore formed initially from magmatic plumes and later enriched by magmatic-metamorphic-modified meteoric *** balance calculations indicate mineralisation by combined leaching and precipitation,with an average iron enrichment factor of>2.67 and SiO_(2)depletion factor of>*** is associated with an overall volume reduction of 28.27%,reflecting net leaching and volume collapse of the bIF protholith.

关键词： bulk geochemistry Rb-Sr Sm-Nd Mitzimevin High-grade iron ore

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina bottermann Jana brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Simultaneous determination of typical toxic aldehydes formed during food frying and digestion using isotope dilution UHPLC-QqQ-MS/MS

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Grain & Oil Science and Technology 2024年第1期7卷 42-49页

作者： Feng Wang Yun Cui Dongjie Liu charles brennan Soottawat benjakul Weiwei Cheng Gengsheng Xiao Lukai Ma Key Laboratory of Green Processing and Intelligent Manufacturing of Lingnan Specialty Food of Ministry and Rural Affairs College of Light Industry and FoodZhongkai University of Agriculture and EngineeringGuangzhou 510225China School of Science Royal Melbourne Institute of Technology UniversityMelbourneAustralia International Center of Excellence in Seafood Science and Innovation Faculty of Agro-IndustryPrince of Songkla UniversitySongkhla 90110Thailand College of Food Science and Technology Zhejiang University of TechnologyHangzhou 310014China

An isotope dilution ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed to simultaneously detect two typical kinds ofα,β-unsaturated aldehydes,namely 4-hydroxy-2-hexenal(4-HHE)and 4-hydroxy-2-nonenal(4-HNE),in *** proposed method exhibited a linear range of 10-1000 ng/mL with a limit of detection of 0.1-2.0 ng/g and a limit of quantification of 0.3-5.0 ng/*** recovery rates of these typical toxic aldehydes(i.e.,4-HHE,4-HNE)and their d3-labeled analogues were 91.54%-105.12%with a low matrix ***,this proposed method was successfully applied to a real frying system and a simulated digestion system,wherein the contents of 4-HHE and 4-HNE were determined for ***,the obtained results provide strong support for further research into the production of 4-HHE and 4-HNE resulting from foods during oil digestion and frying.

关键词： UHPLC-QqQ-MS/MS 4-Hydroxy-2-hexenal 4-Hydroxy-2-nonenal Frying Simulated digestion

Aging impairs the osteocytic regulation of collagen integrity and bone quality

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bone Research 2024年第1期12卷 78-94页

作者： charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna bons Christina D.King Jordan b.burton birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC berkeley/UCSF Graduate Program in bioengineering San FranciscoCA 94143USA buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity