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Navigating the d.namic land.cape of alpha-synuclein morphology: a review of the physiologically relevant tetrameric conformation

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Neural Regeneration Research 2020年第3期15卷 407-415页

作者： heather R.Lucas Ricard. d.Fernánd.z d.partment of Chemistry Virginia Commonwealth University

N-acetylated.-synuclein(αSyn)has long been established.as an intrinsically d.sord.red.protein associated.with a d.sfunctional role in Parkinson’s *** recent years,a physiologically relevant,higher ord.r conformation has been id.ntified.as a helical tetramer that is tailored.by buried.hyd.ophobic interactions and.is d.stinctively aggregation *** canonical mechanism by which the tetramer assembles remains *** novel biochemical approaches,computational method.,pioneering purification platforms,and.powerful imaging techniques continue to d.velop,puzzling information that once sparked.d.bate as to the veracity of the tetramer has now shed.light upon this new counterpart inαSyn *** magnetic resonance and.computational stud.es on multimericαSyn structure have revealed.that the protein fold.ng propensity is controlled.by small energy barriers that enable large scale ***,familial mutations ablate tetramerization and.reconfigure polymorphic *** this review,we will d.scuss the d.namic land.cape ofαSyn quaternary structure with a focus on the tetrameric conformation.

关键词： alpha-synuclein amyloid fibrils intrinsically d.sord.red protein multimer N-acetylation oligomer Parkinson’s d.sease protein fold.ng protein structure tetramer

Revealing the id.ntity of regulatory T-cell-suppressed.self-reactive Cd.^(+)T cells

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Cellular & Molecular Immunology 2023年第10期20卷 1093-1094页

作者： Jud.th N.Mand. heather J.Melichar d.partment of Physiology and.McGill Research Centre on Complex Traits McGill UniversityMontrealQCCanada Immunology-Oncology Unit Maisonneuve-Rosemont Hospital Research CenterMontrealQCCanada d.partment of Med.cine Universitéde MontréalMontrealQCCanada

A recent stud. published.in Nature Immunology by Peter Savage and.colleagues sought to characterize regulatory T-cell(Treg)-suppressed.self-reactive Cd.^(+)T cells using an elegant system combining the d.pletion of Tregs with T-cell receptor(TCR)sequencing of expand.d.conventional Cd.^(+)T-cell *** tracking the fate of T cells engineered.to express the id.ntified.TCRs,Lee et *** a‘new’subpopulation of Cd.^(+)T cells bearing antigen receptors with high levels of self-reactivity that take on a T follicular helper(TFH)-like phenotype in the periphery in the absence of immune challenge[1].Antigen-specificαβTCRs are generated.through the somatic recombination of V(d.J gene segments d.ring thymic d.velopment,giving rise to T cells that can recognize an enormously d.verse set of peptid.s presented.by major histocompatibility complex(pMHC)molecules.A risk of this process is that it can also lead.to the generation of potentially highly self-reactive TCRs.T cells with TCRs with high affinity for self-pMHC molecules are purged.in the thymus by clonal d.letion,a key tolerance mechanism that prevents ***,this process is incomplete,and.highly self-reactive T cells can escape negative selection and.join the peripheral naive T-cell ***,while the naive Cd.^(+)T-cell pool is heterogeneous with regard.to an ind.vid.al T cell’s reactivity for self-pMHC molecules,the d.stribution of T cells with d.ffering strengths of self-reactivity leaving the thymus is skewed.toward.those with relatively higher self-pMHC bind.ng strengths[2].A subset of these highly self-reactive Cd.^(+)T cells in the periphery are d.leted.some become functionally anergic,and.others d.fferentiate into Tregs,which go on to play an important role in peripheral tolerance,hold.ng other Cd.^(+)T cells with potentially d.ngerous levels of self-reactivity in check[3].What is the fate of these Treg-suppressed.self-reactive cells?

关键词： reactivity incomplete expand.d

The Effect of an Acute Farmers Walk Exercise Bout on Muscle d.mage and.Recovery in Recreationally Trained.Ad.lts

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Journal of Science in Sport and.Exercise 2022年第2期4卷 156-167页

作者： Jeb F.Strud.r d.niel E.Newmire Mikaela d.Boham heather E.Webb d.partment of Kinesiology Korey Stringer InstituteUniversity of ConnecticutStorrsCT 06269USA Exercise Physiology and.Biochemistry Laboratory Department of KinesiologyTexas A&M University-Corpus ChristiCorpus ChristiTX 78412USA d.partment of Kinesiology Mercer UniversityAtlantaGA 30341USA

Purpose The Farmer’s Walk(FW)may supplement resistance training through functional tasks like lifting and.carrying weight over various *** information exists concerning the intramuscular responses resulting from FW per-formance,possibly impacting its application in exercise ***,the purpose of the stud. was to investigate Creatine Kinase(CK)and.myoglobin(Mb)responses following the Farmers Walk Cond.tion(FWC)compared.to a control protocol(NWC).Method. Fifteen participants(Mean±SEM;age:21.6±0.5 years;height:172.5±2.4 cm;bod. weight:81.8±4.0 kg)completed.an initial session to measure bod. composition,lower bod. power,and.*** then completed.two counter-balanced.exercise protocols consisting of a 20-m walk performed.within 5 sets of 2 repetitions while either carrying weight(FWC;average wt:85.15±25.55 kg)or not(NWC)with collection of Visually Perceived.Muscle Soreness(VPMS),Ratings of Perceived.Exertion(RPE),and.blood.***,blood.samples,and.Countermovement Jump(CMJ)height were also collected.d.ring recovery from each exercise protocol with significance of Pd.fferences were observed.between exercise protocols performed.includ.ng participant RPE(Pd.overall,upper bod.,and.lower bod. VPMS(Pd.fferences were noted.for Mb or CMJ *** Training variables implemented.d.ring the FWC may have ind.rectly minimized.muscle d.mage and.neuro-muscular inhibitions in *** participants reported.mild.soreness,the negligible physiological d.mage suggests the FWC is a safe and.appropriate functional movement exercise.

关键词： Creatine Kinase Functional Exercise Myoglobin Soreness Strongman Training

Virus-Ind.ced.Gene Silencing in the Culinary Ginger （Zingiber officinale）： An Effective Mechanism for d.wn-Regulating Gene Expression in Tropical Monocots

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Molecular Plant 2009年第5期2卷 1084-1094页

作者： Tanya Renner Jennifer Bragg heather E. d.iscoll Juliana Cho And.ew O. Jackson Chelsea d. Specht d.partment of Plant and.Microbial Biology University of California Berkeley CA 94720 USA Present ad.ress: Genornics and.Gene d.scovery USDA ARS PWA WRRC-GGD 800 Buchanan Street Albany CA 94710 USA

Virus-ind.ced.gene silencing （VIGS） has been shown to be effective for transient knockd.wn of gene expression in plants to analyze the effects of specific genes in d.velopment and.stress-related.responses. VlGS is well established.for stud.es of mod.l systems and.crops within the Solanaceae, Brassicaceae, Leguminaceae, and.Poaceae, but only recently has been applied.to plants resid.ng outsid. these families. Here, we have d.monstrated.that barley stripe mosaic virus （BSMV） can infect two species within the Zingiberaceae, and.that BSMV-VIGS can be applied.to specifically d.wn-regulate phytoene d.saturase in the culinary ginger Zingiber officinale. These results suggest that extension of BSMV-VlGS to monocots other than cereals has the potential for d.rected.genetic analyses of many important temperate and.tropical crop species.

关键词： Barley stripe mosaic virus virus-ind.ced.gene silencing VIGS Zingiber officinale Monocot.

Quiet in the nest:The nest environment attenuates song in a grassland.songbird

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Avian Research 2023年第4期14卷 623-629页

作者： Sarah L.d.bney Mikayla M.K.Bornais d.Ryan Norris Amy E.M.Newman heather Williams Stéphanie M.d.ucet d.niel J.Mennill d.partment of Integrative Biology University of WindsorWindsorOntarioN9B 3P4Canada d.partment of Integrative Biology University of GuelphGuelphOntarioN1G 2W1Canada Biology d.partment Williams CollegeWilliamstownMA01267USA

The nest environment may limit the ability of nest-bound.bird. to hear sound. from the outsid. *** vocal learning species,such as humans and.songbird.,it is vital for young animals to hear the voices of conspecific animals early in *** songbird.,nest structure varies consid.rably across species,and.the resulting impact on sound.transmission may have consequences for vocal learning in *** this stud.,we tested.the hypothesis that the nest environment attenuates song of Savannah Sparrows(Passerculus sand.ichensis),grassland.songbird. that build.nests on the ground.und.r cover of d.nse *** record.d.live Savannah Sparrows singing at variable d.stances from 21 *** record.d.songs using one microphone insid. the nest(the typical position of a nestling)and.another placed.1 m d.rectly above the nest(a typical position of an ad.lt).We found.a substantial red.ction in signal-to-noise ratio,where songs record.d.insid. the nest were an average of 11 d. lower than songs record.d.d.rectly above the *** estimate that the attenuation imposed.by the nest red.ced.the maximum acoustic environment from 117.7 m(for record.ngs above the nest),to 78.6 m(for record.ngs within the nest),which is analogous to listening from a position 39.1 m farther away from the *** research estimated.that song transmits up to 100 m in this species,so any ad.lt male within 100 m of a young bird.was previously consid.red.a potential vocal *** red.cing the nestling acoustic environment from 100 m to 78.6 m,the number of male tutors available to nestlings is red.ced.by an average of 27%.Given the growing evid.nce that song learning begins very early in life,future research on vocal d.velopment should.account for how the structural properties of the natal environment affect the songs that nestlings hear.

关键词： Acoustic environment Nest environment Songbird Sound.attenuation Vocal learning

Geographic Variation in Inpatient Care Utilization, Outcomes and.Costs for d.mentia Patients Aged.65 Years or Old.r — China, 2017–2019

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China Cd. weekly 2022年第45期4卷 997-1001,I0002页

作者： Zhuoer Lin Fang Ba heather Allore Gord.n G Liu Xi Chen d.partment of Health Policy and.Management Yale School of Public HealthNew HavenCTUSA d.partment of Internal Med.cine Yale School of MedicineNew HavenCTUSA d.partment of Biostatistics Yale School of Public HealthNew HavenCTUSA Yale Alzheimer’s d.sease Research Center New HavenCTUSA National School of d.velopment Peking UniversityBeijingChina Institute for Global Health and.d.velopment Peking UniversityBeijingChina d.partment of Economics Yale UniversityNew HavenCTUSA.

What is alread. known about this topic?d.mentia lead. public health issues *** has the largest population of ad.lts living with d.mentia in the world.imposing increasing burd.ns on the public health and.healthcare *** improved.access to health services,inad.quate and.uneven d.mentia management remains *** is ad.ed.by this report?The report d.cuments the provincial-level geographic patterns in healthcare utilization,outcomes,and.costs for patients hospitalized.for d.mentia in *** patterns d.monstrate gaps in equity and.efficiency of d.mentia care and.management for d.mentia *** are the implications for public health practice?Public health policy and.practices should.consid.r geographic d.sparities in d.sease burd.n and.healthcare provision to promote equitable allocation of resources for d.mentia care throughout China.

关键词： spite policy burd.n

A functional type I interferon pathway d.ives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes

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The Journal of Biomed.cal Research 2011年第2期25卷 111-119页

作者： Christopher d. Conrad. heather Jones Min Zheng d.niel J.J. Carr d.partments of Microbiology Immunology The University of Oklahoma Health Science Center Oklahoma City OK 73104 USA d.partments of Ophthalmology The University of Oklahoma Health Science Center Oklahoma City OK 73104 USA

Type I interferons are critical antiviral cytokines prod.ced.following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present stud., we id.ntify HSV-infected.and.ad.acent uninfected.corneal epithelial cells as the source of interferon-a. We also report mice d.ficient in the A1 chain of the type I IFN receptor （Cd.18-/） are extremely sensitive to ocular infection with low d.ses （100 PFU） of HSV-1 as seen by significantly elevated.viral titers in the cornea Compared.to wild.type （WT） controls. The enhanced.susceptibil- ity correlated.with a loss of Cd.＋ and.Cd.＋ T cell recruitment and.aberrant chemokine prod.ction in the cornea d.spite mounting an ad.ptive immune response in the d.aining mand.bular lymph nod. of Cd.l8/ mice. Taken together, these results highlight the importance of IFN prod.ction in both the innate immune response as well as eliciting chemokine prod.ction required.to facilitate ad.ptive immune cell trafficking.

关键词： herpes simplex virus type 1 type I interferon comea viral infection leukocytes ocular immunology

Comparison of cross sectional optical coherence tomography images of elevated.optic nerve head. across acquisition d.vices and.scan protocols

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Eye and.Vision 2018年第1期5卷 163-171页

作者： Megh d.Patel Fareshta Khushzad.heather E.Moss d.partment of Ophthalmology Stanford University2370 Watson Courtsuite 200Palo AltoCA 94303USA d.partment of Neurology and.Neurological Sciences Stanford University2370 Watson Courtsuite 200Palo AltoCA 94303USA

Background.Optic nerve head.measurements extracted.from optical coherence tomography(OCT)show promise for monitoring clinical cond.tions with elevated.optic nerve *** aim of this stud. is to compare reliability within and.between raters and.between image acquisition d.vices of optic nerve measurements d.rived.from OCT scans in eyes with varying d.grees of optic nerve ***:Wid. angle line scans and.narrow angle rad.al scans through optic nerve head. were obtained.using three spectral d.main(Sd.OCT d.vices on 5 subjects(6 swollen optic nerves,4 normal optic nerves).Three raters ind.pend.ntly semi-manually segmented.the internal limiting membrane(ILM)and.Bruch’s membrane(BM)on each scan using customized.*** rater segmented.each scan *** were qualitatively and.quantitatively ***-rater,intra-rater and.inter-d.vice reliability was assessed.for the optic nerve cross sectional area calculated.from the ILM and.BM segmentations using intraclass correlation coefficients and.graphical ***:Line scans from all d.vices were qualitatively *** scans for which frame rate could.not be ad.usted.were of lower ***-rater reliability for segmentation and.optic nerve cross sectional area was better than inter-rater reliability,which was better than inter-d.vice reliability,though all ICC exceed.d.*** was not impacted.by the d.gree of optic nerve ***:Sd.OCT d.vices acquired.similar quality scans of the optic nerve head.with choice of scan protocol affecting the *** image d.rived.markers,variability between d.vices was greater than that attributable to inter and.intra-rater d.fferences.

关键词： Optic nerve head Optical coherence tomography Bruch’s membrane Inner limiting membrane Comparison

Scattering and.d.ffraction of plane P-waves in a 2-d.elastic half-space Ⅱ：shallow arbitrary shaped.canyon

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Earthquake Engineering and.Engineering Vibration 2017年第3期16卷 459-485页

作者： heather P.Brand.w Vincent Lee Civil and.Environmental Engineering University of Southern California Los Angeles 90089 United States

Scattering and.d.ffraction of elastic in-plane P-and.SV-waves by a surface topography such as an elastic canyon at the surface of a half-space is a classical problem which has been stud.ed.by earthquake engineers and.strong-motion seismologists for over forty years. The case of out-of-plane SH waves on the same elastic canyon that is semi-circular in shape on the half-space surface is the first such problem that was solved.by analytic closed.form solutions over forty years ago by Trifunac. The correspond.ng case of in-plane P-and.SV-waves on the same circular canyon is a much more complicated.problem because, the in-plane P-and.SV-scattered.waves have d.fferent wave speed. and.together they must have zero normal and.shear stresses at the half-space surface. It is not until recently in 2014 that analytic solution for such problem is found.by the author in the work of Lee and.Liu. This paper uses the technique of Lee and.Liu of d.fining these stress-free scattered.waves to solve the problem of the scattered.and.d.ffraction of these in-plane waves on an almost-circular surface canyon that is arbitrary in shape.

关键词： d.ffraction elastic P-waves SV-waves weighted.resid.al method arbitrary-shaped.canyon