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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang amy L.Strong Yuxiao Sun Lei Guo Conan juan Alec C.Bancroft ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard juhoon Lee Sowmya Ramesh Aaron W.james David Hudson Kevin N.Dalby Lin Xu Robert j.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Effects of L-arginine,guanidinoacetic acid and L-citrulline supplementation in reduced-protein diets on bone morphology and mineralization of laying hens

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Animal Nutrition 2023年第3期14卷 225-234页

作者： Hiep Thi Dao amy F.Moss Emma j.Bradbury Robert A.Swick School of Environmental and Rural Science Faculty of ScienceAgricultureBusiness and LawUniversity of New EnglandArmidaleNew South Wales2351Australia Faculty of Animal Science Vietnam National University of AgricultureTrau Quy TownGia Lam DistrictHanoi100000Vietnam Baiada Poultry Pty Limited Pendle HillNew South Wales2145Australia

The alterations in feed ingredients and the nutrient matrix to produce reduced-protein diets may affect bone morphology and mineralization in laying *** study was implemented to determine the effects of L-arginine(Arg),guanidinoacetic acid(GAA),and L-citrulline(Cit)supplementation to Argdeficient reduced-protein diets on bone morphology,strength,and mineralization status of laying *** housed Hy-Line Brown laying hens were evenly distributed to five dietary treatments with 25 replicates per treatment from 20 to 40 wk of *** consisted of a standard protein diet(17%crude protein,SP),a reduced-protein diet deficient in Arg(13%crude protein,RP),and RP supplemented with Arg(0.35%Arg,RP-Arg),GAA(0.46%GAA equivalent to 0.35%Arg,RP-GAA),or Cit(0.35%Cit equivalent to 0.35%Arg,RP-Cit)to reach the Arg level of SP *** fed the SP diet had similar bone weight,ash,length,width,Seedor index,breaking strength,and serum mineral concentration,but higher toe B level(P<0.001)compared to those fed the RP diet at wk *** fed the SP diet consumed more but also excreted more K and B compared to those fed the RP diet(P<0.01).Birds fed the SP diet had lower Cu digestibility(P=0.01)and higher B retention(P<0.01)compared to those offered the RP *** of Arg,GAA,and Cit to the RP diet increased relative femur weight and length(P<0.001).Citrulline supplementation also increased relative tibia and femur ash,and Zn digestibility(P<0.05).Supplementation of GAA to the RP diet decreased serum Ca,P,and Mg levels,decreased tibia Fe and Mg levels and toe Mg level,but increased Al,Fe,Zn,and Mn digestibility(P<0.05).The current findings demonstrated the capacity of laying hens to adapt to low mineral intake by increasing mineral ***,bone morphology and breaking strength,and serum mineral level in laying hens were not influenced by dietary CP *** Arg,GAA,or Cit supplementation were effective in improving bone morphology and

关键词： Ash Breaking strength Femur Low protein Minerals Digestibility

Characterization of Rsg2.a3:A new greenbug resistance allele at the Rsg2 locus from wild barley(Hordeum vulgare ***)

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The Crop journal 2022年第6期10卷 1727-1732页

作者： Xiangyang Xu Dolores Mornhinweg amy Bernardo Genqiao Li Ruolin Bian Brian j.Steffenson Guihua Bai USDA-ARS Wheat Peanutand Other Field Crop Research UnitStillwaterOK 74075USA USDA-ARS Hard Winter Wheat Genetics Research Unit ManhattanKS 66506USA Department of Plant Pathology Kansas State UniversityManhattanKS 66506USA Department of Plant Pathology University of MinnesotaSt.PaulMN 55108USA

Greenbug(Schizaphis graminum Rondani)is a destructive insect pest that not only damages plants,but also serves as a vector for many *** plant resistance is the preferred strategy for managing *** greenbug resistance genes,Rsg1 and Rsg2,have been reported in *** breed cultivars with effective resistance against various greenbug biotypes,additional resistance genes are urgently needed to sustain barley *** barley accession WBDC053(PI 681777)was previously found to be resistant to several greenbug *** this study,a recombinant inbred line(RIL)population derived from Weskan×WBDC053 was evaluated for response to two greenbug biotypes(E and TX1)and genotyped using genotyping by sequencing(GBS).A set of 3347 high quality GBS-derived single nucleotide polymorphisms(SNPs)were then used to map the greenbug resistance gene in this wild barley *** analysis placed the greenbug resistance gene in a 2.35 Mb interval(0-2,354,645 bp)in the terminal region of the short arm of chromosome *** interval harbors 15 genes with leucine-rich-repeat(LRR)protein *** allelism test indicated that the greenbug resistance gene in WBDC053,designated Rsg2.a3,is likely allelic or closely linked to ***-SNPs 2H_1318811and 2H_1839499 co-segregating with Rsg2.a3 in the RIL population were converted to Kompetitive allele specific PCR(KASP)markers KASP-Rsg2.a3-1 and KASP-Rsg2.a3-2,*** two KASP markers can be used to select Rsg2.a3 and have the potential to tag Rsg2 in barley improvement programs.

关键词： Barley Greenbug resistance gene KASP markers Genotyping by sequencing Linkage mapping

Protease supplementation reduced the heat increment of feed and improved energy and nitrogen partitioning in broilers fed maize-based diets with supplemental phytase and xylanase

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Animal Nutrition 2022年第3期10卷 19-25页

作者： Klint W.McCafferty Mingan Choct Sosthene Musigwa Natalie K.Morgan Aaron j.Cowieson amy F.Moss USDA-ARS Poultry Research Unit School of Environmental and Rural SciencesMississippi State39762United States University of New England ArmidaleNSW2351Australia DSM Nutritional Products Kaiseraugst4303Switzerland

An experiment was conducted to explore the effects of digestible amino acid(dAA)concentrations and supplemental protease on live performance and energy partitioning in *** 308 male broilers(n?288)were distributed into 24 floor pens and offered 1 of 4 dietary treatments with 6 replicates from 1 to 35 d of *** treatments consisted of a 2×2 factorial arrangement with dAA concentrations(standard and reduced[34 g/kg below standard])and supplemental protease(without or with)as the main *** 1,15,28,and 35 d of age,feed and broilerswereweighed to determine live ***20 to 23 d of age,a total of 32 birds(2 birds/chamber,4 replicates)were placed in closed-calorimeter chambers to determine respiratory exchange(heat production,HP),apparent metabolisable energy(AME),retained energy(RE),and net energy(NE).From 29 to 35 d of age,supplemental protease in the reduced-dAA diet decreased broiler feed conversion ratio(FCR)by 5.6 points,whereas protease supplementation in the standard-dAA diet increased FCR by 5.8 *** indirect calorimetry assay revealed that supplemental protease decreased(Pj/***,from 20 to 23 d of age,broilers offered the reduced-dAA diet with supplemental protease had a higher daily body weight gain(BWG)(t10.4%),N intake(t7.1%),and N retention(t8.2%)than those offered the standard-dAA with supplemental *** offered the reduced-dAA without supplemental protease exhibited a 3.6%higher AME-to-crude protein(CP)ratio than those offered other *** supplementation in the standard-and reduced-dAA diets resulted in 2.7%and 5.6%lower AME intake-to-N retention ratios,respectively,compared with the unsupplemented ***-dAA increased(P<0.05)AME intake(t4.8%),RE(t9.8%),NE intake(t5.8%),NE intake-to-CP ratio(t3.0%),and RE fat-to-RE ratio(t8.6%).Protease supplementation increased(P<0.05)respiratory quotient(t1.2%)and N retention-to-N intake ratio(t2.2%),

关键词： Exogenous enzyme Mono-component protease Net energy Amino acid

Genomic location of Gb1, a unique gene conferring wheat resistance to greenbug biotype F

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作物学报:英文版 2023年第5期11卷 1595-1599页

作者： Xiangyang Xu Genqiao Li Guihua Bai Brett FCarver Ruolin Bian amy Bernardo jScott Armstrong USDA-ARS Wheat Peanutand Other Field Crop Research UnitStillwaterOK 74075USA USDA-ARS Hard Winter Wheat Genetics Research Unit ManhattanKS 66506USA Department of Agronomy Kansas State UniversityManhattanKS 66506USA Department of Plant and Soil Sciences Oklahoma State UniversityStillwaterOK 74078USA

Greenbug(Schizaphis graminum, Rondani) is a serious insect pest in many wheat growing regions and has been infesting cereal crops in the USA for over a century. Continuous occurrence of new greenbug biotypes makes it essential to explore all greenbug resistant sources available to manage this pest. Gb1, a recessive greenbug resistance gene in DS28A, confers resistance to several economically important greenbug biotypes and is the only gene found to be resistant to greenbug biotype F. A set of 174 F_(2:3)lines from the cross DS28A × Custer was evaluated for resistance to greenbug biotype F in 2020 and 2022. Selective genotyping of the corresponding F_(2) population using single nucleotide polymorphism(SNP) markers generated by genotyping-by-sequencing(GBS) led to the identification of a candidate genomic region for Gb1. Thus, SSR markers previously mapped in this region were used to genotype the entire F2population,and kompetitive allele specific PCR(KASP) markers were also developed from SNPs in the target ***1 was placed in the terminal region of the short arm of chromosome 1A, and its location was confirmed in a second population derived from the cross DS28A × PI 697274. The combined data analysis from the two mapping populations delimited Gb1 to a < 1 Mb interval between 13,328,200 and 14,241,426 bp on1AS.

关键词： Wheat Greenbug resistance gene Gb1 KASP markers Linkage analysis Genotyping-by-sequencing

Stochastic SIS metapopulation models for the spread of disease among species in a fragmented landscape

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International journal of Biomathematics 2016年第4期9卷 97-119页

作者： amy j. Ekanayake Department of Mathematics Western Illinois University 1 University Circle Maeomb Illinois 61455 USA

Two stochastic models are derived for a susceptible–infectious–susceptible epidemic spreading through a metapopulation: a continuous time Markov chain (CTMC) model and an Itô stochastic differential equation (SDE) model. The stochastic models are numerically compared. Close agreement suggests that computationally intense CTMC simulations can be approximated by simpler SDE simulations. Differential equations for the moments of the SDE probability distribution are also derived, the steady states are solved numerically using a moment closure technique, and these results are compared to simulations. The moment closure technique only coarsely approximates simulation results. The effect of model parameters on stability of the disease-free equilibrium is also numerically investigated.

关键词：随机微分方程种群模型疾病传播 SIS 连续时间马尔可夫链近似模拟异质景观

Negative consequences of reduced protein diets supplemented with synthetic amino acids for performance,intestinal barrier function,and caecal microbiota composition of broiler chickens

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Animal Nutrition 2023年第2期13卷 216-228页

作者： Reza Barekatain Peter V.Chrystal Tanya Nowland amy F.Moss Gordon S.Howarth Thi Thu Hao Van Robert j.Moore South Australian Research and Development Institute Roseworthy CampusRoseworthySAAustralia School of Animal and Veterinary Sciences Roseworthy CampusUniversity of AdelaideRoseworthySAAustralia School of Science RMIT UniversityBundoora West CampusBundooraVICAustralia School of Environmental and Rural Science University of New EnglandArmidaleNSWAustralia School of Envi1ronmental and Rural Science University of New EnglandArmidaleNSWAustralia

The consequences of feeding broiler chickens with reduced protein(RP)diets for gut health and barrier function are not well *** study was performed to elucidate the effect of reducing dietary protein and source of protein on gut health and performance *** experimental diets included 2 control diets with standard protein levels either containing meat and bone meal(CMBM)or an all-vegetable diet(CVEG),a medium RP diet(17.5%in growers and 16.5%in finisher),and a severe RP diet(15.6%in grower and 14.6%in finisher).Off-sex Ross 308 birds were assigned to each of the 4 diets and performance measurements were taken from d 7 to 42 *** diet was replicated 8 times(10 birds per replicate).A challenge study was conducted on additional 96 broilers(24 birds per diet)from d 13 to *** of the birds in each dietary treatment were challenged by dexamethasone(DEX)to induce a leaky *** birds with RP diets decreased weight gain(Pjected ***-bacteria was the main phylum driving the differences in birds fed 15.6%*** the family level,Bifidobacteriaceae,Unclassified Bifidobacteriales,Enterococcaceae,Enterobacteriaceae,and Lachnospir-aceae were the main taxa in birds fed 15.6%*** supplementation of synthetic amino acids,severe reduction of dietary pro

关键词： Gut health Microbiota Tight junction protein Inflammation Broiler

A sting in the tail： the N-terminal domain of the androgen receptor as a drug target

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Asian journal of Andrology 2016年第5期18卷 687-694页

作者： amy E Monaghan Iain j McEwan School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB25 2ZD United Kingdom.

The role of androgen receptor （AR） in the initiation and progression of prostate cancer （PCa） is well established. Competitive inhibition of the AR ligand-binding domain （LBD） has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain （NTD） of the AR has been shown to be critical for AR function. Its modular activation function （AF-1） is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-O01 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in PCa progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in PCa.

关键词： androgen receptor inhibitor intrinsically disordered structure N-terminal domain prostate cancer small molecules

Biosurfactant-assisted phytoremediation of potentially toxic elements in soil:Green technology for meeting the United Nations Sustainable Development Goals

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Pedosphere 2022年第1期32卷 198-210页

作者： Songita SONOWAL amy R.NAVA Sanket j.jOSHI Siddhartha Narayan BORAH Nazim F.ISLAM Soumya PANDIT Ram PRASAD Hemen SARMA Department of Botany School of Life SciencesMahatma Gandhi Central UniversityMotihari 845401India Department of Molecular&Cellular Physiology Stanford UniversityStanfordCA 94305SA Oil&Gas Research Center Central Analytical and Applied Research UnitSultan Qaboos UniversityMuscat 123Oman Centre for the Environment Indian Institute of Technology GuwahatiGuwahati 781039India Institutional Biotech Hub(IBT Hub) Department of BotanyNanda Nath Saikia CollegeTitabar 785630India Department of Life Sciences School of Basic Sciences and ResearchSharda UniversityGreater Noida 201306India

Biosurfactants are biomolecules produced by microorganisms, low in toxicity, biodegradable, and relatively easy to synthesize using renewable waste substrates. Biosurfactants are of great importance with a wide and versatile range of applications, including the bioremediation of contaminated sites. Plants may accumulate soil potentially toxic elements(PTEs), and the accumulation efficacy may be further enhanced by the biosurfactants produced by rhizospheric microorganisms. Occasionally, the growth of bacteria slows down in adverse conditions, such as highly contaminated soils with PTEs. In this context,the plant's phytoextraction capacity could be improved by the addition of metal-tolerant bacteria that produce biosurfactants. Several sources, categories,and bioavailability of PTEs in soil are reported in this article, with the focus on the cost-effective and sustainable soil remediation technologies, where biosurfactants are used as a remediation method. How rhizobacterial biosurfactants can improve PTE recovery capabilities of plants is discussed, and the molecular mechanisms in bacterial genomes that support the production of important biosurfactants are listed. The status and cost of commercial biosurfactant production in the international market are also presented.

关键词： bacterial genome metal-tolerant bacteria phytoextraction technology plant growth-promoting rhizobacteria rhizospheric microorganism