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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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An Intelligent MCGDM Model in Green Suppliers Selection Using Interactional Aggregation Operators for Interval-Valued Pythagorean Fuzzy Soft Sets

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1829-1862页

作者： Rana Muhammad Zulqarnain Wen-Xiu Ma Imran Siddique Hijaz Ahmad Sameh Askar School of Mathematical Sciences Zhejiang Normal UniversityJinhua321004China Department of Mathematics and Statistics University of South FloridaTampaFL 33620-5700USA School of Mathematical and statistical Sciences North-West UniversityMafikeng CampusMmabatho2735South Africa Department of Mathematics University of SargodhaSargodha40100Pakistan section of Mathematics International Telematic University UninettunoCorso Vittorio Emanuele IIRoma00186Italy Near East University Operational Research Center in HealthcareNicosia/Mersin99138Turkey Department of Statistics and Operations Research College of ScienceKing Saud UniversityRiyadh11451Saudi Arabia

Green supplier selection is an important debate in green supply chain management(GSCM),attracting global attention from scholars,especially companies and *** frequently search for new ideas and strategies to assist them in realizing sustainable *** of the speculative character of human opinions,supplier selection frequently includes unreliable data,and the interval-valued Pythagorean fuzzy soft set(IVPFSS)provides an exceptional capacity to cope with excessive fuzziness,inconsistency,and inexactness through the decision-making *** main goal of this study is to come up with new operational laws for interval-valued Pythagorean fuzzy soft numbers(IVPFSNs)and create two interaction operators-the intervalvalued Pythagorean fuzzy soft interaction weighted average(IVPFSIWA)and the interval-valued Pythagorean fuzzy soft interaction weighted geometric(IVPFSIWG)operators,and analyze their *** operators are highly advantageous in addressing uncertain problems by considering membership and non-membership values within intervals,providing a superior solution to other ***,specialist judgments were calculated by the MCGDM technique,supporting the use of interaction AOs to regulate the interdependence and fundamental partiality of green supplier assessment ***,a statistical clarification of the planned method for green supplier selection is presented.

关键词： Interval-valued Pythagorean fuzzy soft set IVPFSIWA operator IVPFSIWG operator MCGDM SCM

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Genome-wide association study identifies 12 new genetic loci associated with growth traits in pigs

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Journal of Integrative Agriculture 2024年第1期23卷 217-227页

作者： Mu Zeng Binhu Wang Lei Liu Yalan Yang Zhonglin Tang Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding/Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes School of Life Science and EngineeringFoshan UniversityFoshan 528231China Kunpeng Institute of Modern Agriculture at Foshan Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesFoshan 528200China Shenzhen Branch Guangdong Laboratory of Lingnan Modern Agriculture/Key Laboratory of Livestock and Poultry Multi-omics of Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China

Growth traits are among the most important economic traits in pigs and are regulated by polygenes with complex regulatory *** the major indicators of growth performance,the backfat thickness(BFT),loin eye area(LEA),and days to 100 kg(D100)traits are commonly used to the genetics improvement in ***,the available genetic markers for these traits are *** uncover novel loci and candidate genes associated with growth performance,we collected the phenotypic information of BFT,LEA,and D100 in 1,186 pigs and genotyped all these individuals using the Neogen GGP porcine 80K *** performed a genome-wide association study(GWAS)using 4 statistical models,including mixed linear models(MLM),fixed and random model circulating probability unification(FarmCPU),settlement of MLM under progressively exclusive relationships(SUPER),Bayesian-information and linkage-disequilibrium Iteratively nested keyway(Blink),and identified 5,3,and 6 high-confidence single nucleotide polymorphisms(SNPs)associated with BFT,LEA,and D100,*** annotation and quantitative trait locus(QTL)mapping analysis suggested that6 genes(SKAP2,SATB1,PDE7B,PPP1R16B,WNT3,and WNT9B)were potentially associated with growth performance in *** analysis suggested that the expression of Src Kinase Associated Phosphoprotein 2(SKAP2)was higher in prenatal muscles than in postnatal muscles,and the expression of Phosphodiesterase 7B(PDE7B)continuously increased during the prenatal stages and gradually decreased after birth,implying their potential roles in prenatal skeletal muscle ***,this study provides new candidate loci and genes for the genetic improvement of pigs.

关键词： GWAS pig growth trait QTL mapping skeletal muscle

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Advances on methods for mapping QTL in plant

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Science Bulletin 2006年第23期51卷 2809-2818页

作者： ZHANG Yuan-Ming section on statistical genomics, State Key Laboratory of Crop Genetics and Germplasm Enhancement/National Center for Soybean Improvement, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China section on statistical genomics State Key Laboratory of Crop Genetics and Germplasm Enhancement/National Center for Soybean Improvement College of Agriculture Nanjing Agricultural University Nanjing China

Advances on methods for mapping quantitative trait loci (QTL) are firstly summarized. Then, some new methods, including mapping multiple QTL, fine mapping of QTL, and mapping QTL for dynamic traits, are mainly described. Finally, some future prospects are proposed, including how to dig novel genes in the germplasm resource, map expression QTL (eQTL) by the use of all markers, phenotypes and micro-array data, identify QTL using genetic mating designs and detect viability loci. The purpose is to direct plant geneticists to choose a suitable method in the inheritance analysis of quantitative trait and in search of novel genes in germplasm resource so that more potential genetic information can be uncovered.

关键词： quantitative trait locus parameter estimation effect maximum likelihood method Bayesian method.

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Pressure Measurements from Five Different Nosebands at Rest, and During Riding at Walk, a Collected Gait, Backing up and a Full Stop

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Open Journal of Veterinary Medicine 2024年第6期14卷 137-154页

作者： Adrian Harrison Dept for Veterinary and Animal Sciences (IVH) Faculty of Health & Medical Sciences University of Copenhagen PAS Section for Physiology Frederiksberg Denmark

Background: Scientific procedures for addressing noseband fit and tightness, eliminating the risk of excessive and painful tightening, as well as quantitative measurements of pressures under the noseband while riding are either scarce or lacking. Purpose/Aim: To assess simple means of measuring pressure under different nosebands with a view to their adoption as scientific methodology. Method: Horses (n = 7) were fitted with five different bridles (A-E). Pressure distribution and intensity were measured using colour sensitive film (Fujifilm LLLW), assessing the level of pressure and distribution across the surface of the nosebands, as assessed and ranked by independent assessors. A CURO system was also used to measure pressure in real-time under nosebands whilst riding. Results: The colour-sensitive film for D & B were ranked 1st and 2nd, respectively. Regularity of pressure overall showed a statistical difference between nosebands (A & B significantly more unregular than the others). Pressure measurements revealed significantly different means (all P Conclusions: Pressures under nosebands can reach levels that appear capable of inflicting tissue damage, hence bridles and nosebands should be assessed using scientific methodology and not based on arbitrary and subjective criteria, as is currently the case.

关键词： Noseband Welfare Pain Bridle Fit Riding Tölt FEI

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Genome-wide mapping of QTL associated with heterosis in the RIL-based NCIII design

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Chinese Science Bulletin 2012年第21期57卷 2655-2665页

作者： HE XiaoHong HU ZhongLi ZHANG Yuan-Ming section on statistical genomics State Key Laboratory of Crop Genetics and Germplasm Enhancement&Chinese National Center for Soybean ImprovementCollege of AgricultnreNanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Hybrid Rice College of Life SciencesWuhan UniversityWuhan 430072China

Heterosis represents one of the most revolutionary advancements in crop *** the genetic dissection of heterosis,NCIII design is one of the most powerful and widely used mating ***,the methodologies for quantitative trait loci (QTL) detection in the design were mostly based on composite interval ***,in this study,our purpose was to develop a statistical method for mapping epistatic QTL associated with heterosis in the RIL-based NCIII ***,we derivated the expectations of two classical linear transformations,Z 1 and Z 2,while a quantitative trait was controlled by two QTL with digenic epistasis and arbitrary linkage under the F ∞ and F 2 metric ***,we constructed an epistatic genetic model that includes all markers on the whole genome simultaneously,and estimated all the parameters in the model by the empirical Bayes ***,a series of Monte Carlo simulation experiments was carried out to confirm the proposed *** results show that:(1) all the augmented genetic parameters for main-effect QTL could be rightly identified with satisfactory statistical power and precision;(2) the statistical powers in the detection of augmented epistatic effects were substantively affected by the signs of pure epistatic effects;(3) it is more difficult to detect epistatic QTL than to detect main-effect QTL;(4) statistical power is higher in the RIL-based NCIII design than in the F 2-based NCIII design,especially in the detection of the augmented epistatic effect that consists of two pure epistatic effects in opposite directions.

关键词：数量性状位点全基因组杂种优势设计测绘上位性效应统计方法复合区间作图

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Emerging role of microRNAs in lipid metabolism

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Acta Pharmaceutica Sinica B 2015年第2期5卷 145-150页

作者： Zhihong Yang Tyler Cappello Li Wang Department of Physiology and Neurobiology and the Institute for Systems Genomics University of Connecticut Veterans Affairs Connecticut Healthcare System Department of Internal Medicine Section of Digestive Diseases Yale University

micro RNAs(mi RNAs or mi Rs) are small non-coding RNAs that are involved in posttranscriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that mi RNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of mi RNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of mi RNAs expression. We emphasized on several representative mi RNAs that are functionally involved into lipid metabolism, including mi R-33/33 n, mi R122, mi R27a/b, mi R378/378 n, mi R-34 a and mi *** the function of mi RNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.

关键词： Lipid metabolism microRNAs Nuclear receptors

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Gilbert's syndrome: High frequency of the (TA)_7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene

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World Journal of Gastroenterology 2006年第14期12卷 2269-2275页

作者： Shabana Farheen Sanghamitra Sengupta Amal Santra Suparna Pal Gopal Krishna Dhali Meenakshi Chakravorty Partha P Majumder Abhijit Chowdhury Human Genetics Unit Indian statistical Institute KolkataIndia Department of Gastroenterology Institute of Postgraduate Medical Education & Research KolkataIndia Human Genetics & genomics Division Indian Institute of Chemical Biology KolkataIndia

AIM： To identify the variants in U rase 1 （UGT1A1） gene in Gilbert＇s syndrome （GS） and to estimate the association between homozygosity for TA insertion and GS in India, as well as the frequency of TA insertion and its impact among normal controls in India. METHODS： Ninety-five GS cases and 95 normal controls were selected. Liver function and other tests were done. The promoter and all 5 exons of UGT1A1 gene were resequenced. Functional assessment of a novel trinucleotide insertion was done by in silico analysis and by estimating UGT1A1 promoter activity carried out by ludferase reporter assay of appropriate constructs in Hep G2 cell line. RESULTS： Among the GS patients, 80% were homozygous for the TA insertion, which was several-fold higher than reports from other ethnic groups. The mean UCB level was elevated among individuals with only one copy of this insertion, which was not significantly different from those with two copies. Many new DNA variants in UGT1A1 gene were discovered, including a trinucleotide （CAT） insertion in the promoter found in a subset （10%） of GS patients, but not among normal controls. In-silico analysis showed marked changes in the DNA-folding of the promoter and functional analysis showed a 20-fold reduction in transcription efficiency of UGT1A1 gene resulting from this insertion, thereby significantly elevating the UCB level. CONCLUSION： The genetic epidemiology of GS is variable across ethnic interactions among UGT1A1 groups and the epistatic promoter variants modulate bilirubin glucuronidation.

关键词： Unconjugated hyperbilirubinemia UGT1A1 gene DNA resequencing Luciferase reporter assay

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Genomic Mosaicism of the Brain:Origin,Impact,and Utility

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Neuroscience Bulletin 2024年第6期40卷 759-776页

作者： Jared H.Graham Johannes C.M.Schlachetzki Xiaoxu Yang Martin W.Breuss Department of Pediatrics Section of Clinical Genetics and MetabolismUniversity of Colorado School of MedicineAurora80045-2581COUSA Department of Cellular and Molecular Medicine University of California San DiegoLa Jolla92093-0021San DiegoCAUSA Department of Neurosciences University of California San DiegoLa Jolla92093-0021San DiegoCAUSA Rady Children’s Institute for Genomic Medicine San Diego92123CAUSA

Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic ***,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth *** recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental ***,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and *** the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our *** will provide current definitions and an overview of contemporary detection approaches for genomic ***,we will discuss the impact and utility of genomic mosaicism.

关键词： genomics Brain development Brain homeostasis Genomic mosaicism

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AluScanCNV2:An R package for copy number variation calling and cancer risk prediction with next-generation sequencing data

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Genes & Diseases 2019年第1期6卷 43-46页

作者： Taobo Hu Si Chen Ata Ullah Hong Xue Division of Life Science Applied Genomics Centre and Centre for Statistical ScienceHong Kong University of Science and TechnologyClear Water BayHong Kong School of Basic Medicine and Clinical Pharmacy China Pharmaceutical UniversityNanjingChina

The usage of next-generation sequencing(NGS)to detect copy number variation(CNV)is widely accepted in cancer *** on an AluScanCNV software developed by us previously,an AluScanCNV2 software has been developed in the present study as an R package that performs CNV detection from NGS data obtained through AluScan,wholegenome sequencing or other targeted NGS *** applications would include the expedited usage of somatic CNVs for cancer subtyping,and usage of recurrent germline CNVs to perform machine learning-assisted prediction of a test subject’s susceptibility to cancer.

关键词： AluScan Bioinformatics Cancer subtyping Cancer predisposition Machine learning

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