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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

Dairy cows inoculated with highly pathogenic avian influenza virus H5N1

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四川生理科学杂志 2024年第10期46卷 2275-2275页

作者： amy l Baker Virus and Prion Research Unit National Animal Disease Center Agricultural Research Service United States Department of Agriculture Ames Iowa USA National Veterinary Services laboratories Animal and Plant Health Inspection Service United States Department of Agriculture Ames Iowa USA Veterinary Diagnostic and Production Animal Medicine Iowa State University Ames Iowa USA

Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.***.4.4b was detected in the United States in *** HPAI viruses caused mortality events in poultry,wild birds,and wild *** March 25,2024,HPAI H5N1 clade 2.***.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 *** case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium.A single transmission event,likely from birds,was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.***.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating *** were inoculated by aerosol respiratory route and cows by intramammary *** disease was mild in heifers,but infection was confirmed by virus detection,lesions,and *** disease in lactating cows included decreased rumen motility,changes to milk appearance,and production *** was confirmed by high levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and *** study provides the foundation to investigate additional routes of infection,pathogenesis,transmission,and intervention strategies.

关键词： H5N1 cows fir

Perioperative use of immunosuppressive medications in patients with Crohn’s disease in the new"biological era"

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Gastroenterology Report 2017年第3期5卷 165-177,I0001页

作者： amy l.lightner Bo Shen Division of Colon and Rectal Surgery Mayo ClinicRochesterMinnesotaMNUSA Center for Inflammatory Bowel Diseases Digestive Disease and Surgery Institutethe Cleveland Clinic FoundationClevelandOHUSA

Crohn’s disease(CD)is characterized by transmural inflammation of the gastrointestinal tract leading to inflammatory,stricturing and/or and fistulizing *** a patient develops medically refractory disease,mechanical obstruction,fistulizing disease or perforation,surgery is ***,surgery is not curative in most cases,underscoring the importance of bowel preservation and adequate perioperative medical *** many of the medications used to treat CD are immunosuppressive,the concern for postoperative infectious complications and anastomotic healing are particularly concerning;these concerns have to be balanced with preventing and treating residual or recurrent *** herein review the available literature and make recommendations regarding the preoperative,perioperative and postoperative administration of immunosuppressive medications in the current era of biological therapy for *** algorithms for perioperative medical management would greatly assist future research for optimizing surgical outcomes and preventing disease recurrence in the future.

关键词： Crohn’s disease biological therapy perioperative period medical management

The ascent of immune checkpoint inhibitors： is the understudy ready for a leading role？

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Cancer Biology & Medicine 2017年第4期14卷 341-347页

作者： amy l. Cummings Edward B. Garon Department of Hematology and Oncology David Geffen School of Medicine at the University of California Los Angeles 90095 USA

The recent approval of pembrolizumab as second-line treatment for any solid tumor with high-level microsatellite instability or mismatch repair deficiency agnostic of tissue and origin1 has shattered a glass ceiling for immune checkpoint *** longer bound to a specific cancer diagnosis but rather a biomarker,pembrolizumab has heightened a burgeoning optimism towards the drug *** how these agents should carve out additional

关键词： PD The ascent of immune checkpoint inhibitors:is the understudy ready for a leading role PFS OS ORR IHC

Variation in floral form of CRISPR knock-outs of the poplar homologs of lEAFY and AGAMOUS after FT heat-induced early flowering

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Horticulture Research 2023年第8期10卷 183-193页

作者： amy l.Klocko Estefania Elorriaga Cathleen Ma Steven H.Strauss Department of Biology University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Forest Ecosystems and Society Oregon State UniversityCorvallisOR 97331USA

Plant migration and gene flow from genetically modified or exotic trees to nearby lands or by crossing with wild relatives is a major public and regulatory *** genetic strategies exist to mitigate potential gene flow;however,the long delay in onset of flow-ering is a severe constraint to research *** used heat-induced FT overexpression to speed assessment of the expected floral phenotypes after CRISPR knockout of poplar homologs of the key floral genes,lEAFY and *** selected events with previously characterized CRISPR-Cas9 induced biallelic changes then re-transformed them with the Arabidopsis thaliana FlOWERING lOCUS T(AtFT)gene under control of either a strong constitutive promoter or a heat-inducible *** successfully obtained flowering in both a male and female clone of poplar,observing a wide range of inflorescence and floral forms among flowers,ramets,and insertion ***,flowers obtained from the selected lFY and AG targeted events were consistent with what would be predicted for loss-of-function of these ***-targeted events showed small catkins with leaf-like organs,AG-targeted events had nested floral organs consistent with reduction in floral determinacy and absence of well-formed carpels or *** findings demonstrate the great developmental plasticity of Populus flowers during genetically accelerated flowering,which may be of horticultural *** also provide an informative early view of floral phenotypes and apparent sterility from knockouts of both these gene targets.

关键词： AGAMOUS flowers organs

Visual classification of feral cat Felis silvestris catus vocalizations

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Current Zoology 2017年第3期63卷 331-339页

作者： Jessica l. OWENS Mariana OlSEN amy FONTAINE Christopher KlOTH Arik KERSHENBAUM Sara WAllER Cooperative Predator Vocalization Consortium South Daytona FL 32119 Department of Philosophy Montana State University Bozeman MT 59717 Department of Wildlife Humboldt State University Arcata CA 95521 Department of Philosophy University of Nevada Reno NV 89503 USA Department of Zoology University of Cambridge Cambridge CB2 3E J UK

Cat vocal behavior, in particular, the vocal and social behavior of feral cats, is poorly understood, as are the differences between feral and fully domestic cats. The relationship between feral cat social and vocal behavior is important because of the markedly different ecology of feral and domestic cats, and enhanced comprehension of the repertoire and potential information content of feral cat calls can provide both better understanding of the domestication and socialization process, and improved welfare for feral cats undergoing adoption. Previous studies have used conflicting classi- fication schemes for cat vocalizations, often relying on onomatopoeic or popular descriptions of call types （e.g., ＂miow＇）. We studied the vocalizations of 13 unaltered domestic cats that complied with our behavioral definition used to distinguish feral cats from domestic. A total of 71 acoustic units were extracted and visually analyzed for the construction of a hierarchical classification of vocal sounds, based on acoustic properties. We identified 3 major categories （tonal, pulse, and broadband） that further breakdown into 8 subcategories, and show a high degree of reliability when sounds are classified blindly by independent observers （Fleiss＇ Kappa K= 0.863）. Due to the limited behavioral contexts in this study, additional subcategories of cat vocalizations may be identified in the future, but our hierarchical classification system allows for the addition of new categories and new subcategories as they are described. This study shows that cat vocalizations are diverse and complex, and provides an objective and reliable classification system that can be used in future studies.

关键词： bioacoustics communication socialization spectrograms.

Structural analysis of flagellar axonemes from inner arm dynein knockdown strains of Trypanosoma brucei

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BIOCEll 2012年第3期36卷 133-141页

作者： RANDI ZUKAS AlEX J.CHANG MARIAN RICE amy l.SPRINGER Department of Biology Amherst CollegeAmherstMAUSA Department of Biological Sciences Mount Holyoke CollegeSouth HadleyMAUSA

Trypanosoma brucei is a protozoan flagellate that causes African sleeping *** function in this organism is critical for life cycle progression and pathogenesis,however the regulation of flagellar motility is not well *** flagellar axoneme produces a complex beat through the pre-cisely coordinated firing of many proteins,including multiple dynein *** motors are found in the inner arm and outer arm *** are studying one of the inner arm dynein motors in the *** flagellum:*** knockdown of genes for two components of dynein-f:DNAH10,theαheavy chain,and IC138,an intermediate chain,cause severe motility defects including *** determine if motility defects result from structural disruption of the axoneme,we used two different flagellar preparations to carefully examine axoneme structure in these strains using transmission electron microscopy(TEM).Our analysis showed that inner arm dynein size,axoneme structural integrity and fixed central pair orientation are not significantly different in either knockdown culture when compared to control *** results support the idea that immotility in knockdowns affecting DNAH10 or IC138 results from loss of dynein-f function rather than from obvious structural defects in the axoneme.

关键词： Flagellar motility transmission electron microscopy central pair

Coal energy and environmental impacts:Introduction

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Energy Geoscience 2021年第2期2卷 87-89页

作者： luis F.O.Silva amy l.Wolfe Department of Civil and Environmental.Universidad de la Costa CUCCalle 58#55e66BarranquillaAtlanticoColombia Kentucky Geological Survey University of Kentucky216 Mining and Mineral Resources Building504 Rose StreetLexingtonKY40506-0107USA

Within the last decade,the importance of integrating the envi-ronment,people,and climate has transitioned from being an aca-demic concern(e.g..WEF,2011)into a broadly societal concern asthe forecasted realities of environmental deterioration and globalclimate change come to pass,creating urgent public and environ-mental health issues.

关键词： has integrating environ

Twenty years of drought-mediated change in snag populations in mixed-conifer and ponderosa pine forests in Northern Arizona

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Forest Ecosystems 2021年第2期8卷 265-277页

作者： Joseph l.Ganey Jose M.Iniguez Scott C.Vojta amy R.Iniguez US Forest Service Rocky Mountain Research Station2500 S.Pine KnollAZ 86001 FlagstaffUSA

Background:Snags(standing dead trees)are important biological legacies in forest systems,providing numerous resources as well as a record of recent tree *** 1997 to 2017,we monitored snag populations in drought-influenced mixed-conifer and ponderosa pine(Pinus ponderosa)forests in northern ***:Snag density increased significantly in both forest *** increase was driven largely by a pulse in snag recruitment that occurred between 2002 and 2007,fol owing an extreme drought year in 2002,with snag recruitment returning to pre-pulse levels in subsequent time *** later years during the study also were warmer and/or drier than average,but these years were not as extreme as 2002 and did not trigger the same level of snag *** recruitment was not equal across tree species and size classes,resulting in significant changes in species composition and size-class distributions of snag populations in both forest *** trees were far more abundant than snags in these forests,the effect of this mortality pulse on tree populations was far smal er than its effect on snag *** loss rates increased over time during the study,even though many snags were newly *** may reflect the increasing prevalence of white fir snags and/or snags in the smal er size classes,which general y decay faster than snags of other species or larger ***,although total numbers of snags increased,many of the newly recruited snags may not persist long enough to be valuable as nesting substrates for native ***:Increases in snag abundance appeared to be due to a short-term tree mortality"event"rather than a longerterm pattern of elevated tree *** mortality event fol owed a dry and extremely warm year(2002)embedded within a longer-term *** models suggest that years like 2002 may occur with increasing frequency in the southwestern *** years may result in additional mortality pulses,wh

关键词： Climate change Drought Monitoring Snag abundance Snag creation Snag dynamics Species composition Tree mortality