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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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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul madley-Dowd Harriet Forbes Jessica Rast Caichen Zhong Renee m Gardner Christina Dalman kristen Lyal cRAIG Newschaffer Torbjorn Tomson michael Lundberg Daniel Berglind Neil m Davies Brian K Lee Cecilia magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community medicine Region StockholmStockholmSweden K.G Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,pmore pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,pm mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

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SWEET as Sugar： New Sucrose Effluxers in Plants

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molecular Plant 2012年第4期5卷 766-768页

作者： R. Frank Baker kristen A. Leach David m. Braun Division of Biological Sciences Interdisciplinary Plant Group Missouri Maize Center University of Missouri 110 Tucker Hall Columbia MO 65211

Photosynthesis leads to the fixation of carbon in leaves and to the accumulation of carbohydrates （e.g., sucrose, starch）. This assimilated carbon must be transported from the leaves （source tissues） to non-photosynthetic organs （sink tissues）, such as roots and seeds. Despite the essentiality of this process in plants, a complete understanding of the actors involved in sucrose export from leaves is lacking. SWEET proteins are a newly identified class of sugar transporters that facilitate dif- fusion of sugars across cell membranes down a concentration gradient. In this perspective, we highlight the recent publica- tion of Chen et al. （2012）, which reports that SWEET proteins transport sucrose across cell membranes, are expressed in a subset of phloem parenchyma cells,

关键词： Candy foliage sugar protein sweeteners plants Fueling actor Carbon Fixation Saccharose snow goose

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Geochemistry of the volcanic rocks from Bioko Island(“Cameroon Hot Line”)： Evidence for plume-lithosphere interaction

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Geoscience Frontiers 2016年第5期7卷 743-757页

作者： Fadimatou Ngounouno Yamgouot Bernard Déruelle Isaac Bertrand Gbambié mbowou Ismaila Ngounouno Daniel demaiffe Departement des Sciences de la Terre Faculte des Sciences Universite de Ngaoundere B.P. 454 Ngaoundere Cameroon Laboratoire de magmatologie et Ceochimie lnorganique et Experimentale (mAGIE) Institut de Physique du Globe de Paris UMR 7154 Universite Pierre et Marie Curie 4 place Jussieu 75252 Paris cedex 05 France Departement des mines et de la Geologie Ecole de Geologie et d'Exploitation Miniere (EGEM) Universite de Ngaoundere B.R 115 Meiganga Cameroon Laboratoire de Geochimie lsotopique et Geodynamique Chimique DSTE (CP 160/02) Universite Libre de Bruxelles 50 av. Roosevelt 1050 BruxellesBelgium

Bioko Island（3008 m a.s.l） is located in the presently more active volcanic zone of the Cameroon Line and composed essentially of alkaline basalts and hawaiites, and lesser mugearites. The rocks show microlitic porphyritic texture with phenocrysts of olivine（83% 〈 Fo 〈 87%） and clinopyroxene in a matrix of plagioclase, clinopyroxene and oxides. Hawaiites and mugearites also include phenocrysts of plagioclase（An62-67Ab35-32Or3-1）. major element variation diagrams show an increase in Si O2, Al2O3, Na2 O and K2 O with increasing mg O for the studied rock groups. The rocks are characterized by low（^86Sr/^87Sr）i ratios（0.70320e0.70406）, high 3Nd（t） values（2.56e4.33） and high（^206Pb/^204Pb）i ratios（20.032e20.035） *** are enriched in LILE and LREE, and have（Hf/Sm）N= 0.57e1.16. These geochemical signatures are similar to those of the mount Cameroon rocks, and might be attributed to low degrees of partial melting from a garnet-amphibole-bearing mantle source. The trace elements and isotopic compositions suggest that the parental magma source might have involved HImU- and Em1-components.

关键词： Geochemistry HImU-Em1 Volcanic rocks Bioko Cameroon Hot Line

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Kidney disease in patients with chronic liver disease:Does sex matter?

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World Journal of Clinical Cases 2023年第17期11卷 3980-3992页

作者： Katherine m Cooper Alessandro Colletta kristen moulton Kenneth m Ralto Deepika Devuni Department of medicine UMass Chan Medical SchoolWorcesterMA 01665United States Department of medicine Division of GastroenterologyUMass Chan Medical SchoolWorcesterMA 01665United States Department of medicine Division of Renal MedicineUMass Chan Medical SchoolWorcesterMA 01665United States

Kidney disease in patients with liver disease is serious and increases *** to 50%of patients hospitalized experience an episode of acute kidney *** general,men with liver disease are thought to be at increased risk of kidney ***,this association should be considered with caution because most studies use creatinine-based inclusion criteria,which is negatively biased against *** this review,we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.

关键词： Sex differences Renal disease Gender disparity Hepatorenal syndrome Renal replacement therapy

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Sucrose transporter2 contributes to maize growth,development,and crop yield

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Journal of Integrative Plant Biology 2017年第6期59卷 390-408页

作者： kristen A.Leach Thu m.Tran Thomas L.Slewinski Robert B.meeley David m.Braun Division of Biological Sciences Interdisciplinary Plant Group Missouri Maize Center University of Missouri Columbia MO 65211 USA Department of Biology Pennsylvania State University University Park PA 16802 USA DuPont Pioneer Research & Development Johnston Iowa 50131 USA

During daylight, plants produce excess photo- synthates, including sucrose, which is temporarily stored in the vacuole. At night, plants remobilize sucrose to sustain metabolism and growth. Based on homology to other sucrose transporter （SUT） proteins, we hypothesized the maize （Zea mays） SUCROSE TRANSPORTER2 （ZmSUT2） protein functions as a sucrose/H^＋ symporter on the vacuolar membrane to export transiently stored sucrose. To understand the biological role of ZmSut2, we examined its spatial and temporal gene expression, determined the protein subcellular localization, and characterized loss-of- function mutations. ZmSut2 mRNA was ubiquitously expressed and exhibited diurnal cycling in transcript abundance. Expressing a translational fusion of ZmSUT2 fused to a red fluorescent protein in maize mesophyll cell protoplasts revealed that the protein localized to the tonoplast. Under field conditions, zmsut2 mutant plants grew slower, possessed smaller tassels and ears, and produced fewer kernels when compared to wild-type siblings, zmsut2 mutants also accumulated two-fold more sucrose, glucose, and fructose as well as starch in source leaves compared to wild type. These findings suggest （i） ZmSUT2 functions to remobilize sucrose out of the vacuole for subsequent use in growing tissues; and （ii） its function provides an important contribution to maize development and agronomic yield.

关键词： William J. Lucas, University of California, Davis, USAReceived Dec. 30, 2016 Accepted Feb. 10, 20171 Online on Feb. 16,2017

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microbiological cultures and antimicrobial prophylaxis in patients undergoing total pancreatectomy with islet cell autotransplantation

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Hepatobiliary & Pancreatic Diseases International 2023年第4期22卷 426-429页

作者： kristen R Szempruch Anne m Lachiewicz Brittney m Williams Aman Kumar Xavier Baldwin Chirag S Desai Pharmacy Department University of North Carolina Medical CenterChapel HillNCUSA Division of Infectious Disease University of North Carolina Medical CenterChapel HillNCUSA Department of Surgery TransplantUniversity of North Carolina Medical CenterChapel HillNCUSA

To the Editor:Total pancreatectomy with islet cell autotransplantation(TPIAT)is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic *** procedure involves surgical removal of the entire pancreas,isolation of islet cells and reinfusion of these cells into the liver via portal vein[1,2].The risk of contamination to the final islet cell product can occur at several stages of the isolation procedure[3].In order to ensure the sterility of the islet cell product,multiple samples from the preservation and cannulation solution,and the final islet cell product are sent for bacterial *** studies have found variable clinical consequences of these cultures on infectious com-plications or graft function[3-9].Herein we aimed to determine the incidence of infection in 60 days post-TPIAT and its association with the culture data.

关键词： islet patients viable

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The unfolded protein response signaling and retinal müller cell metabolism

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Neural Regeneration Research 2018年第11期13卷 1861-1870页

作者： kristen Kelly Joshua J.Wang Sarah X.Zhang Department of Ophthalmology and Neuroscience Program Ross Eye InstituteUniversity at BuffaloState University of New York SUNY Eye Institute State University of New YorkBuffaloNYUSA

The retina is one of the most energy demanding tissues in the body. Like most neurons in the central nervous system, retinal neurons consume high amounts of adenosine-5′-triphosphate（ATP） to generate visual signal and transmit the information to the brain. Disruptions in retinal metabolism can cause neuronal dysfunction and degeneration resulting in severe visual impairment and even blindness. The homeostasis of retinal metabolism is tightly controlled by multiple signaling pathways, such as the unfolded protein response（UPR）, and the close interactions between retinal neurons and other retinal cell types including vascular cells and müller glia. The UPR is a highly conserved adaptive cellular response and can be triggered by many physiological stressors and pathophysiological conditions. Activation of the UPR leads to changes in glycolytic rate, ATP production, de novo serine synthesis, and the hexosamine biosynthetic pathway, which are considered critical components of müller glia metabolism and provide metabolic support to surrounding neurons. When these pathways are disrupted, neurodegeneration occurs rapidly. In this review, we summarize recent advance in studies of the UPR in müller glia and highlight the potential role of the UPR in retinal degeneration through regulation of müller glia metabolism.

关键词： unfolded protein response retina müller glia metabolism neurodegeneration X-box binding protein 1 glycolysis glucose transporter

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Enhanced disinfection of Escherichia coli and bacteriophage mS2 in water using a copper and silver loaded titanium dioxide nanowire membrane

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Frontiers of Environmental Science & Engineering 2016年第4期10卷 71-79页

作者： Guiying RAO kristen S. BRASTAD Qianyi ZHANG Rebecca ROBINSON Zhen HE Ying LI Department of mechanical Engineering Texas A&M University College Station TX 77843 USA Department of mechanical Engineering University of Wisconsin-Milwaukee Milwaukee WI 53211 USA A.O. Smith Corporate Technology Center Milwaukee WI 53224 USA Department of Civil and Environmental Engineering Virginia Polytechnic Institute and State University Blacksburg VA 24061 USA

Titanium dioxide （TiO2） is a widely used photocatalyst that has been demonstrated for microorganism disinfection in drinking water. In this study, a new material with a novel structure, silver and copper loaded TiO2 nanowire membrane （Cu-Ag-TiO2） was prepared and evaluated for its efficiency to inactivate E. coli and bacteriophage mS2. Enhanced photo-activated bactericidal and virucidal activities were obtained by the Cu-Ag-TiO2 membrane than by the TiO2, Ag-TiO2 and Cu-TiO2 membranes under both dark and UV light illumination. The better performance was attributed to the synergies of enhanced membrane photoacfivity by loading silver and copper on the membrane and the synergistic effect between the free silver and copper ions in water. At the end of a 30 min test of dead- end filtration under 254 nm UV irradiation, the Cu-Ag-TiO2 membrane was able to obtain an E. coli removal of 7.68 log and bacteriophage ms2 removal of 4.02 log, which have met the US EPA standard. The free metal ions coming offthe membrane have concentrations of less than 10 ppb in the water effluent, far below the US EPA maximum contaminant level for silver and copper ions in drinking water. Therefore, the photo-activated disinfection by the Cu-Ag-Ti02 membrane is a viable technique for meeting drinking water treatment standards of microbiological water purifiers.

关键词： Photo-activated disinfection Titanium dioxide Nanowire membrane Silver Copper

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Immediate and long-term effects of invasive plant species on soil characteristics

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Soil Ecology Letters 2022年第3期4卷 276-288页

作者： Irene m.Unger Robert J.Kremer kristen S.Veum Keith W.Goyne Department of Biology and Chemistry Baker UniversityP.O.Box 65Baldwin CityKS 66006USA School of Natural Resources University of missouri 302 ABNR Bldg.ColumbiaMO 65211USA USDA-ARS Cropping Systems and Water Quality UnitUniversity of Missouri302 ABNR Bldg.ColumbiaMO 65211USA Department of Forest Resources and Environmental Conservation Virginia Tech324 Cheatham HallBlacksburgVA 24061USA

Invasive plant species may alter soil characteristics or interact with the soil microbial community resulting in a competitive *** objectives were to determine:i)if invasive plant species alter soil properties;and ii)the long-term effects of invasive plant species on soil properties and subsequent implications on ecological restoration *** focused on Lespedeza cuneata,a plant that may be *** samples were collected from four locations in Central missouri,USA:an old-field with abundant ***,two reconstructed sites,and a remnant prairie that has never been *** health indictors were used to characterize soil properties at these *** every soil property differed significantly between the unplowed prairie reference site and the other three *** reconstructed sites,however,generally did not differ from the invaded *** results indicate that the reconstructed prairies are not fully *** above-ground traits,such as the plant community structure,appear similar to the prairie,the soil microbial community structure still resembles that of an invaded old-field *** results indicate that more time may be needed before soil microbial populations fully recover after invasive plant removal.

关键词： Sericea lespedeza Legacy effects Soil microorganisms

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