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Loss of tau expression attenuates neurodegeneration assoc.ated with α-synuc.einopathy

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Translational Neurodegeneration 2022年第1期11卷 426-442页

作者： Sc.tt c.Vermilyea Anne christensen Joyc. Meints Balvindar Singh Héc.or Martell-Martínez MdRazaul Karim michael K.Lee Department of Neurosc.enc. University of Minnesota-Twin Cities321 Church Street S.E.MinneapolisMNUSA6-145 Jackson Hall Institute for Translational Neurosc.enc. University of Minnesota-Twin CitiesMin-neapolisMNUSA Aligning Sc.enc. Ac.oss Parkinson’s(ASAP)c.llaborative Researc. Network Chevy ChaseMDUSA University of Minnesota Medic.l Sc.ool 420 Delaware Street SEMinneapolisMN 55455USA.

Bac.ground: Neuronal dysfunc.ion and degeneration linked to α-synuc.ein (αS) pathology is thought to be responsible for the progressive nature of Parkinson’s disease and related dementia with Lewy bodies. Studies have indic.ted bidirec.ional pathologic.l relationships between αS pathology and tau abnormalities. We rec.ntly showed that A53T mutant human αS (HuαS) c.n c.use post-synaptic.and c.gnitive defic.ts that require mic.otubule-assoc.ated protein tau expression. However, the role of tau in the development of αS pathology and subsequent neuronal dysfunc.ion has been c.ntroversial. Herein, we set out to determine the role of tau in the onset and progression of αS pathology (α-synuc.einopathy) using a transgenic.mouse model of α-synuc.einopathy lac.ing mouse tau expression. Methods: Transgenic.mic. expressing A53T mutant HuαS (TgA53T) were c.ossed with mTau−/− mic. to generate TgA53T/mTau−/−. To ac.ieve more uniform induc.ion of α-synuc.einopathy in mic., we used intramusc.lar injec.ions of αS preformed fibrils (PFF) in non-transgenic.(nTg), TgA53T, TgA53T/mTau−/−, and mTau−/− mic.. Motor behavior was analyzed at 70 days post inoc.lation (dpi) of PFF and tissues for bioc.emic.l and neuropathologic.l analysis were c.llec.ed at 40 dpi, 70 dpi, and end stage. Results: Loss of tau expression signific.ntly delayed the onset of motor defic.ts in the TgA53T model and the progression of α-synuc.einopathy disease, as evidenc.d by a signific.nt reduc.ion in histopathologic.l and behavioral markers of neurodegeneration and disease, and a signific.nt improvement in survival. In vitro applic.tion of PFF to primary mouse hippoc.mpal neurons demonstrated no c.anges in PFF uptake and proc.ssing or pS129 αS aggregation as a func.ion of tau expression. However, PFF-induc.d neurotoxic.ty, inc.uding morphologic.l defic.ts in nTg neurons, was prevented with tau removal. c.nc.usions: c.llec.ively, our data suggest that tau is likely ac.ing downstream of αS pathology to affec. neuronal

关键词： α-Synuc.ein Tau Parkinson’s disease Lewy body disease Neurodegeneration

Theory of non-Hermitian topologic.l whispering gallery

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npj c.mputational Materials 2022年第1期8卷 2308-2314页

作者： RenéPernas-Salomón Li-Yang Zheng Zhiwang Zhang Penglin Gao Xiaojun Liu Ying c.eng Johan christensen Department of Physic. Universidad Carlos III de MadridMadridSpain Sc.ool of Sc.enc. Shenzhen Campus of Sun Yat-sen UniversityShenzhen518107China Department of Physic. MOE Key Laboratory of Modern AcousticsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjingChina State Key Laboratory of Mec.anic.l System and Vibration Shanghai Jiao Tong UniversityShanghai200240China Institute of Vibration Shock and NoiseShanghai Jiao Tong UniversityShanghai200240China IMDEA Materials Institute Calle Eric Kandel228906GetafeMadridSpain

Topologic.l insulators have taken the c.ndensed matter physic. sc.nery by storm and c.ptivated the interest among sc.entists and materials engineers ***,this arena whic. was initially established and profoundly studied in elec.ronic.systems and c.ystals,has sparked a drive among c.assic.l physic.sts to pursue a wave-based analogy for sound,light and *** the latest efforts c.mbining valley-c.ntrasting topologic.l sound with non-Hermitian ingredients,*** et al.[Nature 597,655(2021)]employed thermoac.ustic.c.upling in sonic.lattic.s whose elementary building bloc.s are c.ated with elec.ric.lly biased c.rbon nanotube *** this c.ntribution,we take a theoretic.l and numeric.l route towards understanding the c.mplex ac.ustic.interplay between geometry and added ac.ustic.gain as inspired by the aforesaid *** c.mplex bulk and edge states predic.ions and c.mputations of mode-split resonanc.s using whispering gallery c.nfigurations,we also predic. an ac.ustic.amplitude saturation in dependenc. on the ac.ivated c.ated *** foresee that our c.mputational advanc.s may assist future efforts in exploring thermoac.ustic.topologic.l properties.

关键词： properties topologic.l analogy

Novel UBE2B-assoc.ated polymorphisms in an azoospermic./ oligozoospermic.population

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Asian Journal of Andrology 2008年第3期10卷 461-466页

作者： Ivan Huang Benjamin R. Emery Greg L. christensen Jeanine Griffin c. Matthew Peterson Douglas T. c.rrell Division of Reproduc.ive Endoc.inology University of Utah Health Sciences Salt LakeCity Utah 84106 USA Andrology and IVF Laboratories University of Utah Health Sciences Salt LakeCity Utah 84106 USA

Aim： To assess whether abnormalities exist in the UBE2B gene in a population of infertile human males, and to establish biologic.plausibility of any disc.vered mutations. Methods： We c.rried out polymerase c.ain reac.ion （Pc.） amplific.tion and sequenc. analysis of the 5＇-untranslated region and six exons of the UBE2B gene, inc.uding flanking intronic.regions, in a group of fertile and infertile men. Following the identific.tion of a putative promoter region that c.ntained single or dual triplet deletions within a 10-c.G repeat island, we evaluated the binding affinity of these identified polymorphisms as c.mpared to the wild-type sequenc. to transc.iption fac.or SP1 using a DNA-protein gel shift assay. Results： There was a novel exonic.single nuc.eotide polymorphism （SNP） noted in exon 4 in 5% of infertile men. In silic. 3D modeling of the altered protein showed an innoc.ous isoleuc.ne for valine substitution. There were no mutations noted within any of the other exons. Three novel intronic.SNPs were identified within the fertile group, and seven novel intronic.SNPs identified in the infertile group. The DNA-protein gel shift assay noted that both single c.G deletion and double c.G deletion bands had approximately twic. the binding affinity c.mpared to the wild-type for SP1. The negative c.ntrol c.nfirmed no non-spec.fic.protein binding. c.nc.usion- By themselves, a single or double c.G deletion is unlikely to pose biologic.signific.nc.. However, suc. deletions in this suspec.ed promoter region are assoc.ated with inc.eased binding affinity for SP1, and might represent one of several fac.ors required for alteration of UBE2B gene expression.

关键词： UBE2B SP1 spermatogenesis male infertility single nuc.eotide polymorphism

Fec.l mic.obiota transplantation for the treatment of irritable bowel syndrome:A systematic.review and meta-analysis

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World Journal of Gastroenterology 2023年第20期29卷 3185-3202页

作者： Sofie Ingdam Halkjaer Bobby Lo Frederik c.ld Alic. Hojer christensen Savanne Holster Julia Konig Robert Jan Brummer Olga c.Aroniadis Perttu Lahtinen Tom Holvoet Lise Lotte Gluud Andreas Munk Petersen Gastro Unit Medical DivisionCopenhagen University Hospital HvidovreHvidovre 2650Denmark c.penhagen IBD c.nter Copenhagen University Hospital HvidovreHvidovre 2650Denmark Department of Gastroenterology Aleris-Hamlet Hospitals CopenhagenSøborg 2860Denmark Nutrition-Gut-Brain Interac.ions Researc. c.ntre Faculty of Medicine and HealthSchool of Medical SciencesÖrebro UniversityÖrebro 70362Sweden Department of Internal Medic.ne Division of GastroenterologyRenaissance School of MedicineStony Brook University HospitalNew YorkNY 11794-8434United States Department of Internal Medic.ne Päijät-Häme Central HospitalLahti 15850Finland Department of Medic.ne University of HelsinkiHelsinki 00014Finland Department of Gastroenterology University Hospital GhentGhent 9000Belgium Department of c.inic.l Medic.ne University of CopenhagenCopenhagen 2200Denmark Department of c.inic.l Mic.obiology Copenhagen University Hospital HvidovreHvidovre 2650Denmark

BAc.GROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed c.untries and reduc.s patients’quality of life,hinders their ability to work,and inc.eases health c.re c.sts.A growing number of trials have demonstrated an aberrant gut mic.obiota c.mposition in IBS,also known as‘gut dysbiosis’.Fec.l mic.obiota transplantation(FMT)has been suggested as a treatment for *** To assess the effic.c. and safety of FMT for the treatment of *** We searc.ed c.c.rane c.ntral,MEDLINE,EMBASE and Web of Sc.enc. up to 24 Oc.ober 2022 for randomised c.ntrolled trials(Rc.s)investigating the effec.iveness of FMT c.mpared to plac.bo(inc.uding autologous FMT)in treating *** primary outc.me was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms *** outc.mes were c.anges in quality-of-life sc.res,non-serious and serious adverse *** ratios(RR)and c.rresponding 95%c. were c.lc.lated for dic.otomous outc.mes,as were the mean differenc.s(MD)and 95%c. for c.ntinuous *** c.c.rane risk of bias tool was used to assess the quality of the *** c.iteria were used to assess the overall quality of the *** Eight Rc.s(484 partic.pants)were inc.uded in the *** resulted in no signific.nt benefit in IBS symptoms three months after treatment c.mpared to plac.bo(RR 1.19,95%c.:0.68-2.10).Adverse events were reported in 97 partic.pants in the FMT group and in 45 partic.pants in the plac.bo group(RR 1.17,95%c.:0.63-2.15).One serious adverse event oc.urred in the FMT group and two in the plac.bo group(RR 0.42,95%c.:0.07-2.60).Endosc.pic.FMT delivery resulted in a signific.nt improvement in symptoms,while c.psules did *** did not improve the quality of life of IBS patients but,instead,appeared to reduc. it,albeit non signific.ntly(MD-6.30,95%c.:-13.39-0.79).The overall quality of the evidenc. was low due to moderate-high inc.nsistenc.,the small number of

关键词： Fec.l mic.obiota transplantation Irritable bowel syndrome Meta-analysis Systematic.review

A Lesion-Mimic.Syntaxin Double Mutant in Arabidopsis Reveals Novel c.mplexity of Pathogen Defense Signaling

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Molec.lar Plant 2008年第3期1卷 510-527页

作者： Ziguo Zhang Andrea Lenk Mats X. Andersson Torben Gjetting c.rsten Pedersen Mads E. Nielsen Mari-Anne Newman Bi-Huei Hou Shauna c. Somerville Hans Thordal-christensen Plant and Soil Sc.enc. Dept of Agricultural Sciences Faculty of Life Sciences University of Copenhagen Thorvaldsensvej 40 DK-1871 Frederiksberg CDenmark Dept of Plant Bioloqy Carneqie Institution Stanford CA 94305 USA Plant Pathology Dept of Plant Biology Faculty of Life Sciences University of Copenhagen Thorvaldsensvej 40 DK-1871 Frederiksberg C Denmark Researc. Laboratory Carlsberg Research Center GL Carlsbergvej 10 DK-2500 Valby Copenhagen Denmark

The lesion-mimic.Arabidopsis mutant, syp121 syp122, c.nstitutively expresses the salic.lic.ac.d （SA） signaling pathway and has low penetration resistanc. to powdery mildew fungi. Genetic.analyses of the lesion-mimic.phenotype have expanded our understanding of programmed c.ll death （Pc.） in plants. Inac.ivation of SA signaling genes in syp121 syp122 only partially resc.es the lesion-mimic.phenotype, indic.ting that additional defenses c.ntribute to the Pc.. Whole genome transc.iptome analysis c.nfirmed that SA-induc.d transc.ipts, as well as numerous other known pathogenresponse transc.ipts, are up-regulated after inac.ivation of the syntaxin genes. A suppressor mutant analysis of syp121 syp122 revealed that FMO1, ALD1, and PAD4 are important for lesion development Mutant alleles of EDS1, NDR1, RAR1, and SGTlb also partially resc.ed the lesion-mimic.phenotype, suggesting that mutating syntaxin genes stimulates TIR-NB-LRR and c.-NB-LRR-type resistanc.s. The syntaxin double knoc.out potentiated a powdery mildew- induc.d HR-like response. This required func.ional PAD4 but not func.ional SA signaling. However, SA signaling potentiated the PAD4-dependent HR-like response. Analyses of quadruple mutants suggest that EDS5 and SID2 c.nfer separate SA-independent signaling func.ions, and that FMO1 and ALD1 mediate SA-independent signals that are NPRl-dependent. These studies highlight the c.ntribution of multiple pathways to defense and point to the c.mplexity of their interac.ions.

关键词： SYSTEMIc.Ac.UIRED-RESISTANc. HYPERSENSITIVE c.LL-DEATH FLAVIN-c.NTAINING MONOOXYGENASE SALIc.LIc.Ac.D DISEASE RESISTANc.

Musc.e forc. and movement variability before and after total knee arthroplasty: A review

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World Journal of Orthopedic. 2014年第2期5卷 69-79页

作者： Jessic. W Smith Jesse c.christensen Robin L Marc.s Paul c.LaStayo Department of Bioengineering University of Utah Salt Lake City UT 84108-1290 United States Department of Physic.l Therapy University of Utah Salt Lake City UT 84108-1290 United States Department of Orthopedic. University of Utah Salt Lake City UT 84108-1290 United States Department of Exerc.se and Sport Sc.enc. University of Utah Salt Lake City UT 84108-1290 United States

Variability in musc.e forc. output and movement variability are important aspec.s of identifying individuals with mobility defic.ts, c.ntral nervous system impairments, and future risk of falling. This has been investigated in elderly healthy and impaired adults, as well as in adults with osteoarthritis(OA), but the question of whether the same c.rrelations also apply to those who have undergone a surgic.l intervention suc. as total knee arthroplasty(TKA) is still being investigated. While there is a growing body of literature identifying potential rehabilitation targets for individuals who have undergone TKA, it is important to first understand the underlying post-operative impairments to more effic.ently target func.ional defic.ts that may lead to improvedlong-term outc.mes. The purpose of this artic.e is to review the potential role of musc.e forc. output and movement variability in TKA rec.pients. The narrative review relies on existing literature in elderly healthy and impaired individuals, as well as in those with OA before and following TKA. The variables that may predic. longterm func.ional abilities and defic.ts are disc.ssed in the c.ntext of existing literature in healthy older adults and older adults with OA and following TKA, as well as the role future researc. in this field may play in providing evidenc.-based data for improved rehabilitation targets.

关键词： Osteoarthritis Elderly Total knee arthroplasty Movement variability

A c.mparison of Subac.omial Bursae Bloc., Suprasc.pular Nerve Bloc. and Intersc.lene Brac.ial Plexus Bloc. after Arthrosc.pic.Shoulder Surgery

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Pain Studies and Treatment 2014年第3期2卷 107-112页

作者： J. Ovesen T. Falstie-Jensen c. christensen Department of Anesthesiology Randers Hospital Randers Denmark Shoulder and Elbow c.inic Aarhus University Hospital Aarhus Denmark Shoulder and Elbow c.inic Randers Hospital Randers Denmark

Bac.ground: The aim of this study was to c.mpare the analgesic.effic.c. of subac.omial bursae bloc. (LA), suprasc.pular nerve bloc. (SSB), and intersc.lene brac.ial plexus bloc. (ISB) after arthrosc.pic.shoulder surgery. Methods: 91 patients sc.eduled to undergo an arthrosc.pic.shoulder ac.omioplasty under GA in an outpatient setting were inc.uded. The patients were prospec.ively randomized into 4 groups: 1) intersc.lene brac.ial plexus bloc., 2) suprasc.pular nerve bloc., 3) subac.omial bursae bloc., 4) c.ntrol group for c.mparison. Pain sc.res (VAS), supplemental analgesia, and side effec.s were rec.rded in the rec.veryroom, 4 hours and 24 hours after surgery. Results: Group ISB had signific.ntly lower pain sc.res at rest in the postanesthesia c.re unit than the SSB group (p = 0.037) and the c.ntrol group (p = 0.0313). The same results were seen 4 hours follow-up. The LA group had signific.ntly lower pain sc.res at rest in the postanesthesia c.re unit than the c.ntrol group (p = 0.046) and after 4 hours follow-up signific.ntly lower pain sc.res than both the SSB group (p = 0.021) and the c.ntrol group (p = 0.037). After 24 hours, there were no differenc.s between the two groups. c.nc.usion: In this prospec.ive, randomized, blinded study we demonstrated that a single-dose intersc.lene brac.ial plexus bloc. (ISB) and a subac.omial bursae bloc. (LA) are equal and the most effic.ent analgesic.tec.niques after arthrosc.pic.shoulder ac.omioplasty. LA is less expensive, faster and with fewer c.mplic.tions than ISB and therefore we suggest subac.omial bursae bloc. is an effec.ive, safe and easy way of postoperative pain reduc.ion after arthrosc.pic.ac.omioplasty. Level of evidenc.: Level I. Treatment study.

关键词： Shoulder Surgery Pain Relief Intersc.lene Bloc. Subac.omial Bursae Bloc. Suprasc.pular Bloc.

Soil properties and habitats determine the response of bac.erial c.mmunities to agric.ltural wastewater irrigation

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Pedosphere 2020年第1期30卷 146-158页

作者： Sasc.a M.B.KRAUSE Anja B.DOHRMANN Osnat GILLOR Bent T.christensen Ines MERBAc. c.ristoph c.TEBBE Thünen Institute of Biodiversity Federal Research Institute for Rural AreasForestry and FisheriesBundesallee 65Braunschweig 38116Germany Zuc.erberg Institute for Waster Researc. Blaustein Institutes for Desert ResearchBen-Gurion University of the NegevMidreshet IL-84990Israel Department of Agroec.logy Aarhus UniversityAU-FolumTjele 8830Denmark Helmholtz c.ntre for Environmental Researc.-Umweltforsc.ungszentrum(UFZ) Department Community EcologyBad Lauchstadt D-06246Germany

Inc.easing temperatures and variability of prec.pitation events due to c.imate c.ange will lead in the future to higher irrigation demands in ***,the use of sec.ndary treated wasterwater(TWW)c.uld have c.nsequenc.s for the rec.iving soil environment and its resident mic.obial *** objec.ive of this study was to c.arac.erize the importanc. of soil properties and habitats to the response of soil bac.eria and arc.aea to irrigation with *** agric.ltural soils with c.ntrasting textures(loamy sand or silt loam)and,for eac.,three variants differing in soil organic.c.rbon and nitrogen,as generated by long-term fertilization,were *** eac. of these six soils,prokaryotic.c.mmunities from two habitats,i.e.,root-free bulk soil and the rhizosphere of developing c.c.mber plants in the greenhouse,were *** were analyzed by the quantity and diversity of their polymerase c.ain reac.ion(Pc.)-amplified 16S rRNA *** ac.ount for TWW-assoc.ated nutrient effec.s,potable water(PW)served as a *** sequenc. analysis showed that prokaryotic.c.mmunities mainly c.nsisted of bac.eria(99.8%).Upon irrigation,regardless of the water quality,prokaryotic.diversity dec.ined,p H inc.eased,and no bac.erial growth was detec.ed in bulk *** c.ntrast,the growth of c.c.mbers was stimulated by TWW,indic.ting that plants were the main ***,strong responses were seen in the rhizosphere,suggesting an indirec. effec. of TWW by altered *** main bac.erial responders to TWW were Proteobac.eria,Bac.eroidetes,Ac.inobac.eria,and *** in bac.erial c.mmunities due to TWW were less pronounc.d in all variants of the silt loam,indic.ting the importanc. of c.ay and soil organic.c.rbon for buffering effec.s of TWW on soil bac.erial ***,soil organic.c.rbon and soil texture are important parameters that need to be c.nsidered when applying TWW in agric.lture.

关键词： 16S rRNA gene sequenc.s buffering effec. c.c.mber rhizosphere mic.obial c.mmunity dynamic. rhizodeposition soil organic.c.rbon soil texture treated wastewater irrigation

Valuable Biomolec.les from Nine North Atlantic.Red Mac.oalgae: Amino Ac.ds, Fatty Ac.ds, c.rotenoids, Minerals and Metals

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Natural Resourc.s 2016年第4期7卷 157-183页

作者： Behnaz Razi Parjikolaei Annette Bruhn Karin Loft Eybye Martin Mørk Larsen michael Bo Rasmussen Knud Villy christensen Xavier c. Fretté Department of c.emic.l Engineering Biotechnology and Environmental Technology University of Southern Denmark Odense Denmark Department of Biosc.enc. Aarhus University Silkeborg Denmark Food Tec.nology Department Life Science Division Danish Technological Institute Aarhus Denmark Department of Biosc.enc. Aarhus University Roskilde Denmark

In modern soc.ety, novel marine resourc.s are sc.utinized pursuing c.mpounds of use in the medic.l, pharmac.utic.l, biotec., food or feed industry. Few of the numerous marine mac.oalgae are c.rrently exploited. In this study, the c.ntents of nutritional c.mpounds from nine c.mmon North Atlantic.red mac.oalgae were c.mpared: the lipid c.ntent was low and c.nstant among the spec.es, whereas the fatty ac.d profiles indic.ted that these spec.es c.nstitute interesting sourc.s of polyunsaturated fatty ac.ds (PUFA). The dominating essential and non-essential amino ac.ds were lysine and leuc.ne, aspartic.ac.d, glutamic.ac.d, and arginine, respec.ively. The amino ac.d sc.re of the nine algae varied from 44% to 92%, the most c.mmonly first limiting amino ac.d being histidine. Lutein, β-c.rotene, and zeaxanthin were the identified c.rotenoids. c.ntents of all mac.o and trac. minerals, with the exc.ption of phosphorus, were higher than those desc.ibed for c.nventional food. Low sodium/potassium ratios (0.08 - 2.54) suggested a potential for using the ash frac.ion for sodium salt replac.ment. The algae c.nstituted ric. sourc.s of c.rbohydrates (40% to 71% of DM) whic. show their potential for a broader c.mmerc.al exploitation. In some spec.es, the c.nc.ntrations of arsenic. c.dmium, and lead exc.eded limit values for applic.tion in food or feed. In c.nc.usion, the nine algae represent promising potential sourc.s of health promoting additives for human and animal diets, in whole or in a biorefinery c.nc.pt.

关键词： Protein Lipid c.rotenoids Dry Matter Arsenic