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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

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

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World Journal of Transplantation 2024年第2期14卷 119-125页

作者： Eden m Gallegos Tanner Reed Paige Deville Blake Platt Claudia Leonardi Lillian Bellfi Jessica Dufrene Saad Chaudhary John Hunt Lance Stuke Patrick Greiffenstein Jonathan Schoen Alan marr Anil Paramesh alison A Smith Department of Physiology Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70124United States Department of medicine Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Surgery Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Trauma Surgery Tacoma General HospitalTacoma 98405United States Department of Public Health Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Donation Services Louisiana Organ Procurement AgencyCovingtonLA 70433United States Department of Surgery Tulane Transplant InstituteTulane University School of MedicineNew OrleansLA 70112United States

BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per *** management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management *** studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant *** To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma *** A retrospective review of adult BPODs from a single level 1 trauma center over ten years was *** criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital *** and steroid administration,the number of organs donated,the types of organs donated,and demographic information were *** analyses were performed with Pmet inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient *** to this study include

关键词： Organ donation Trauma Brain death Levothyroxine Hormone replacement therapy Steroids Organ donor Retrospective

Competitive metabolism of L-arginine:arginase as a therapeutic target in asthma

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The Journal of Biomedical Research 2011年第5期25卷 299-308页

作者： Jennifer m.bratt Amir A.Zeki Jerold A.Last Nicholas J.Kenyon Department of Internal medicine Division of Pulmonary and Critical Care and Sleep MedicineUniversity of California

Exhaled breath nitric oxide （NO） is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase （NOS） and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential tox- icity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics.

关键词： nitric oxide L-arginine arginase nor-NOHA nitrosation nitric oxide synthase

Flexible synthesis of high-purity plasmonic assemblies

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Nano Research 2021年第3期14卷 635-645页

作者： Laurent Lermusiaux Anum Nisar alison m.Funston ARC Centre of Excellence in Exciton Science and School of Chemistry Monash UniversityClaytonVIC3800Australia

The self-assembly of nanoparticles has attracted a vast amount of attention due to the ability of the nanostructure to control light at the sub-wavelength scale,along with consequent strong electromagnetic field ***,most approaches developed for the formation of discrete assemblies are limited to a single and homogeneous system,and incorporation of larger or asymmetrical nanoparticles into assemblies with high purity remains a key ***,a simple and versatile approach to assemble nanoparticles of different sizes,shapes,and materials into various discrete homo-or hetero-structures using only two complementary deoxyribonucleic acid(DNA)strands is ***,surface functionalisation using DNA and alkyl-polyethylene glycol(PEG)enables transformation of as-synthesised nanoparticles into readily usable plasmonic building blocks for *** of the DNA coverage enables the production of different assembly types,such as homo-and hetero-dimers,trimers and tetramers and core-satellite structures,which are produced in high purity using electrophoresis *** approach is extended from purely plasmonic structures to incorporate(luminescent)semiconductor nanoparticles for formation of hybrid *** deposited assemblies form a high yield of specific geometrical arrangements,attributed to the van der Waals attraction between *** method will enable the development of new complex colloidal nanoassemblies for biological and optical applications.

关键词： deoxyribonucleic acid(DNA)self-assembly electrophoretic purification nanoparticle assemblies colloidal stability

Consistent individual differences in fathering in threespined stickleback Gasterosteus aculeatus

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Current Zoology 2012年第1期58卷 45-52页

作者： Laura R Stein alison m Bell Department of Animal Biology University of Illinois Urbana-Champaign Urbana IL 61801 USA.

There is growing evidence that individual animals show consistent differences in behavior. For example, individual threespined stickleback fish differ in how they react to predators and how aggressive they are during social interactions with con- specifics. A relatively unexplored but potentially important axis of variation is parental behavior. In sticklebacks, fathers provide all of the parental care that is necessary for offspring survival; therefore paternal care is directly tied to fitness. In this study, we assessed whether individual male sticklebacks differ consistently from each other in parental behavior. We recorded visits to nest, total time fanning, and activity levels of 11 individual males every day throughout one clutch, and then allowed the males to breed again. Half of the males were exposed to predation risk while parenting during the first clutch, and the other half of the males ex- perienced predation risk during the second clutch. We detected dranlatic temporal changes in parental behaviors over the course of the clutch： for example, total time fanning increased six-fold prior to eggs hatching, then decreased to approximately zero. De- spite these temporal changes, males retained their individually-distinctive parenting styles within a clutch that could not be ex- plained by differences in body size or egg mass. moreover, individual differences in parenting were maintained when males re- produced for a second time. males that were exposed to simulated predation risk briefly decreased fanning and increased activity levels. Altogether, these results show that individual sticklebacks consistently differ from each other in how they behave as parents [Current Zoology 58 （1）： 45-52, 2012].

关键词： Paternal care Personality Behavioral syndrome Fathers Temperament Antipredator behavior

Potato aphid macrosiphum euphorbiae performance is determined by aphid genotype and not mycorrhizal fungi or water availability

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Insect Science 2017年第6期24卷 1015-1024页

作者： alison Jane Karley matthew Emslie-Smith alison Elizabeth Bennett Ecological Sciences The James Hutton Institute Invergowrie Dundee UK School of Biology University of St. Andrews St Andrews UK

Intra- and interspecific variation in plant and insect traits can alter the strength and direction of insect-plant interactions, with outcomes modified by soil biotic and abiotic conditions. We used the potato aphid （macrosiphum euphorbiae Thomas） feeding on cultivated Solanum tuberosum and wild Solanurn berthaulti to study the impact of water availability and plant mutualistic arbuscular mycorrhizal （Am） fungi on aphid performance and susceptibility to a parasitoid wasp （Aphidius ervi Haliday）. Plants were grown under glass with live or sterile Am fungal spores and supplied with sufficient or reduced water supply. Plants were infested with 1 of 3 genotypes ofm. euphorbiae or maintained as aphidfree controls; aphid abundance was scored after 1 week, after which aphid susceptibility to A. ervi was assayed explanta. Solarium tuberosum accumulated c. 20% more dry mass than S. berthaultii, and root mass of S. berthaultii was smallest under reduced water supply in the presence of Am fungi. Aphid abundance was lowest on S. berthaultii and highest for genotype ＂2＂ aphids; genotype ＂1＂ aphid density was particularly reduced on S. berthaultii. Aphid genotype ＂1＂ exhibited low susceptibility to parasitism and was attacked less frequently than the other two more susceptible aphid genotypes. Neither Am fungi nor water availability affected insect performance. Our study suggests a fitness trade-offin m. euphorbiae between parasitism resistance and aphid performance on poor quality Solarium hosts that warrants further exploration, and indicates the importance of accounting for genotype identity in determining the outcome of multitrophic interactions.

关键词： Aphidius ervi arbuscular mycorrhizal fungi multitrophic interaction parasitism resistance Solanum spp.

Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy

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World Journal of Gastroenterology 2014年第30期20卷 10620-10627页

作者： John m Rivas Alejro Perez marlow Hernez alison Schneider Ferno J Castro Digestive Disease Center Cleveland Clinic FloridaWestonFL 33331United States Department of Gastroenterology University of Medicine and Dentistry of New JerseyStratfordNJ 08084United States Department of Internal medicine Cleveland Clinic FloridaWestonFL 33331United States

AIm: To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa-free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with ascorbic acid (2-L PEG + Asc) in patients undergoing after... 详细信息

关键词： Bowel preparation Colonoscopy Screening colonoscopy Colon cancer screening

New risk assessment methodology for coal mine excavated slopes

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International Journal of mining Science and Technology 2018年第4期28卷 581-590页

作者： alison mcQuillan Ismet Canbulat Dan Payne Joung Oh School of minerals and Energy Resources Engineering UNSW SydneySydney 2052Australia BHP Billiton Coal Level 11480 Queen StBrisbaneQueensland 4000Australia

This paper presents a new risk assessment methodology for coal mine excavated slopes. This new empirical-statistical *** assessment m. ethodology （SSAm! is intended for use by geotechnical engineers at both the design review and operational stages of a mine＇s life to categonse the risk of an excavated coal mine slope. A likelihood of failure is determined using a new slope stability classification system for excavated coal mine slopes developed using a database of 119 intact and failed case studies sourced from open cut coal mines in Australia. Consequence of failure is based on slope height and stand-off distance at the toe of the excavated slope. Results are presented in a new risk matrix, with slope risk being divided into low, medium and high categories. The SSAm is put forward as a new risk assess- ment methodology to assess the potential for, and consequence of, excavated coal mine slope failure. Unlike existing classification systems, assumptions about the likely failure mode or mechanism are not required. Instead, the SSAm applies an approach which compares the conditions present within the exca- vated slope face, with the known past performance of slopes with similar geotechnical and geometrical conditions, to estimate the slope＇s propensity for failure. The SSAm is novel in that it considers the depo- sitional history of strata in an excavated slope and how this sequence affects slope stability. It is further novel in that it does not require explicit measurements of intact rock, rock mass and/or defect strength to rapidly calculate a slope＇s likelihood of failure and overall risk. Ratings can be determined entirely from visual observations of the excavated slope face. The new SSAm is designed to be used in conjunction with existing slope stability assessment tools.

关键词： Risk assessment Slope stability Open cut coal mine Excavated slope Likelihood of failure

COVID-19 associated liver injury:A general review with special consideration of pregnancy and obstetric outcomes

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World Journal of Gastroenterology 2022年第42期28卷 6017-6033页

作者： Katherine m.Cooper Alessandro Colletta alison m.Asirwatham Tiffany A.moore Simas Deepika Devuni Department of medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01605United States Department of Obstetrics and Gynecology University of Massachusetts Chan Medical SchoolWorcesterMA 01605United States Departments of Pediatrics Psychiatryand Population&Quantitative Health SciencesUniversity of Massachusetts Chan Medical SchoolWorcesterMA 01605United States Division of Gastroenterology and Hepatology University of Massachusetts Chan Medical SchoolWorcesterMA 1605United States

Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** disease 2019(COVID-19)associated liver injury(COVALI)is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 *** profound clinical implications,its pathophysiology is poorly ***,most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research,including pregnant *** manuscript reviews:Clinical features of COVALI,leading theories of COVALI,and existing literature on COVALI during pregnancy,a topic not widely explored in the ***,we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome,and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.

关键词： COVID-19 liver injury Pregnancy Perinatal liver disease Systemic inflammation Special populations