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Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology

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Translational Neurodegeneration 2014年第1期3卷 67-79页

作者： Francisco Pan-Montojo heinz reichmann Neurologische Klinik Klinikum der Ludwig-Maximilians-Universität MünchenMarchioninistr.1581377 MunichGermany Munich Cluster for Systems Neurology(SyNergy) Adolf-Butenandt-Institut Ludwig-Maximilians-Universität MünchenSchillerstr.4480336 MunichGermany Klinik und Poliklinik für Neurologie Carl Gustav Carus University HospitalTU-DresdenFetscherstr.7401307 DresdenGermany

Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous *** associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and *** prevalence of neurodegenerative diseases has increased over the last *** has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of ***,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive *** some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental *** this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more *** conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.

关键词： Idiopathic Parkinson’s disease Environmental toxins Gene-environment interactions Braak’s staging and pathology progression

Parkinson’s disease and translational research

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Translational Neurodegeneration 2020年第4期9卷 547-557页

作者： Elisabeth Dinter Theodora Saridaki Leonie Diederichs heinz reichmann Bjorn H.Falkenburger Department of Neurology Technische Universitat DresdenDresdenGermany Deutsches Zentrum fur Neurodegenerative Erkrankungen DresdenGermany Department of Neurology RWTH University AachenAachenGermany

Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic *** in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous *** this review we discuss current concepts of two major alterations found during the course of the disease:cytoplasmic aggregates of the protein a-synuclein and the degeneration of dopaminergic *** provide an overview of new approaches in this field based on current concepts and latest *** many areas,translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.

关键词： α-Synuclein Pre-formed fibrils Protein aggregates Aggresome Dopamine deficiency Medium spiny neurons Autophagy

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

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Translational Neurodegeneration 2020年第1期9卷 96-104页

作者： heinz reichmann Andrew Lees José-Francisco Rocha Diogo Magalhaes Patrício Soares-da-Silva the OPTIPARK investigators Department of Neurology University of DresdenDresdenGermany University College London Reta Lila Weston InstituteLondonUK Global Parkinson’s Disease Department BIAL–Portela&CA S.ACoronadoPortugal Research and Development Department BIAL–Portela&CA S.Ada Siderurgia Nacional4745-457 S Mamede do CoronadoPortugal Department of Pharmacology and Therapeutics Faculty of MedicineUniversity PortoPortoPortugal MedInUP Center for Drug Discovery and Innovative MedicinesUniversity PortoPortoPortugal 不详

Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal ***,clinical evidence from routine practice is needed to complement the data from the pivotal ***:OPTIPARK(NCT02847442)was a prospective,open-label,single-arm trial conducted in Germany and the UK under clinical practice *** with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3(Germany)or 6(UK)months in addition to their current levodopa and other antiparkinsonian *** primary endpoint was the Clinician’s Global Impression of Change(CGI-C)after 3 *** assessments included Patient Global Impressions of Change(PGI-C),the Unified Parkinson’s Disease Rating Scale(UPDRS),Parkinson’s Disease Questionnaire(PDQ-8),and the Non-Motor Symptoms Scale(NMSS).Safety assessments included evaluation of treatment-emergent adverse events(TEAEs)and serious adverse events(SAEs).Results:Of the 506 patients enrolled,495(97.8%)took at least one dose of *** these,393(79.4%)patients completed 3 months of ***,71.3 and 76.9%of patients experienced any improvement on CGI-C and PGI-C after 3 months,respectively(full analysis set).At 6 months,for UK subgroup only(n=95),85.3%of patients were judged by investigators as improved since commencing *** scores at 3 months showed statistically significant improvements in activities of daily living during OFF(mean±SD change from baseline:?3.0±4.6,p<0.0001)and motor scores during ON(?4.6±8.1,p<0.0001).The mean±SD improvements of?3.4±12.8 points for PDQ-8 and-6.8±19.7 points for NMSS were statistically significant versus baseline(both p<0.0001).Most of TEAEs(94.8%of events)were of mild or moderate *** considered to be at least possibly related to opicapone were reported for 45.1%of patients,with dyskinesia(11.5%)and dry mouth(6.5%)being

关键词： Levodopa Motor fluctuations Open-label Opicapone Parkinson’s disease

Enemies atpeace:Recentprogressin Agrobacterium-mediated cereal transformation

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The Crop Journal 2024年第2期12卷 321-329页

作者： Shaoshuai Liu Ke Wang Shuaifeng Geng Moammar Hossain Xingguo Ye Aili Li Long Mao Karl-heinz Kogel State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Institute of Phytopathology Centre for BioSystemsLand Use and NutritionJustus Liebig UniversityHeinrich Buff-Ring 26-32D-35392GiessenGermany

Agrobacterium tumefaciens mediated plant transformation is a versatile tool for plant genetic engineering following its discovery nearly half a century *** modifications were made in its application to increase efficiency,especially in the recalcitrant major cereals *** breakthroughs in transformation efficiency continue its role as a mainstream technique in CRISPR/Cas-based genome editing and gene *** modifications led to higher transformation frequency and lower but more stable transgene copies with the capability to revolutionize modern *** this review,we provide a brief overview of the history of Agrobacterium-mediated plant transformation and focus on the most recent progress to improve the system in both the Agrobacterium and the host recipient.A promising future for transformation in biotechnology and agriculture is predicted.

关键词： Agrobacterium tumefaciens Cereal species Genome editing Genetic engineering Plant breeding

Interrelationships between Length of the Day, Moon Distance, Phanerozoic Geodynamic Cycles, Tidal Dissipation and Earth’s Core: Review and Analysis

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International Journal of Geosciences 2024年第5期15卷 396-415页

作者： heinz-Jürgen Brink Independent Researcher Hannover Germany

The rotation of the Earth and the related length of the day (LOD) are predominantly affected by tidal dissipation through the Moon and the growth of the Earth’s core. Due to the increased concentration of mass around the rotation axis of the spinning Earth during the growth of the core the rotation should have been accelerated. Controversially the tidal dissipation by the Moon, which is mainly dependent on the availability of open shallow seas and the kind of Moon escape from a nearby position, acts towards a deceleration of the rotating Earth. Measurements of LOD for Phanerozoic and Precambrian times open ways to solve questions concerning the geodynamical history of the Earth. These measurements encompass investigations of growth patterns in fossils and depositional patterns in sediments (Cyclostratigraphy, Tidalites, Stromatolites, Rhythmites). These patterns contain information on the LOD and on the changing distance between Earth and Moon and can be used as well for a discussion about the growth of the Earth’s core. By updating an older paper with its simple approach as well as incorporating newly published results provided by the geoscientific community, a moderate to fast growth of the core in a hot early Earth will be favored controversially to the assumption of a delayed development of the core in an originally cold Earth. Core development with acceleration of Earth’s rotation and the contemporaneous slowing down due to tidal dissipation during the filling of the ocean may significantly interrelate.

关键词： Length of the Day Moon Distance Phanerozoic Geodynamic Cycles Tidal Dissipation Earth’s Core

Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

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Animal Models and Experimental Medicine 2024年第1期7卷 36-47页

作者： Roa'a H.S.Yosief Iqbal M.Lone Aharon Nachshon heinz Himmelbauer Irit Gat-Viks Fuad A.Iraqi Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael School of Molecular Cell Biology and Biotechnology George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael Institute of Computational Biology Department of BiotechnologyUniversity of Natural Resources and Life SciencesMuthgasse 181190 ViennaAustria

Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic *** aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene ***:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with *** tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was *** GENE-E analysis platform was used to generate a clustered heat map ***:Significant variation in body weight changes between CC lines was *** gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight ***,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome ***:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards *** a next step,eQTL analysis will be performed for our RNA-Seq *** candidate genes from our study will be further assessed with a human cohort with aspergillosis.

关键词： aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-Seq

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel Friedrich Karl-heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

高效精准的血浆处理确保每一滴血液制品的充分利用

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流程工业 2024年第8期 44-45页

作者： Markus heinz 星德科

人类血液在许多领域都是至关重要的资源。它不仅在输血过程中扮演重要角色,还是特殊药品的组成部分。血液制品、原料血浆从人类血液中获取,可为治疗多种疾病提供帮助,如血友病、抗原缺陷、新冠肺炎等。这类产品需求量大、制作流程复杂... 详细信息

人类血液在许多领域都是至关重要的资源。它不仅在输血过程中扮演重要角色,还是特殊药品的组成部分。血液制品、原料血浆从人类血液中获取,可为治疗多种疾病提供帮助,如血友病、抗原缺陷、新冠肺炎等。这类产品需求量大、制作流程复杂。生产过程的高精确性可确保患者充分利用每一滴血液制品,不造成浪费。

关键词：血液制品血浆处理解冻与分馏提纯与配置灌装冻干检测

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

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World Journal of Transplantation 2024年第1期14卷 112-119页

作者： Melina Utz Melere Valberto Sanha Marco Farina Carolina Soares da Silva Luiza Nader Cristine Trein Angelica Maria Lucchese Cristina Ferreira Antonio Nocchi Kalil Flavia heinz Feier Department of Hepatology and Liver Transplantation Santa Casa de Porto AlegrePorto Alegre 90050170Brazil Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Brazil Department of Surgical Oncology Santa Rita Hospital/Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil

BACKGROUND Biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed ***,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with *** is still unclear if a previous portoenterostomy has a negative impact on liver transplantation *** To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for *** This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in *** with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior *** variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as *** Cox regression analysis was performed to determine risk factors for portal vein *** and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank *** Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior *** with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver *** group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical *** portoenterostomy

关键词： Hepatic portoenterostomy Biliary atresia Liver transplantation Patient outcome assessment Portal vein Survival