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A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

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Translational Neurodegeneration 2023年第1期12卷 568-571页

作者： Kelsie M.LaBarbera Yvette I.Sheline nicholas j.izzo Carla M.Yuede Lora Waybright Raymond Yurko Hannah M.Edwards Woodrow D.Gardiner Kaj Blennow Henrik Zetterberg Anne Börjesson-Hanson Roger Morgan Charles S.Davis Robert j.Guttendorf Lon S.Schneider Steven DeKosky Harry LeVine III Michael Grundman Anthony O.Caggiano john R.Cirrito Susan M.Catalano Mary E.Hamby Cognition Therapeutics Inc. PittsburghPAUSA University of Pennsylvania PhiladelphiaUSA Washington University St.LouisUSA University of Gothenburg MölndalSweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden Clinical Neurochemistry Laboratory Sahlgrenska University HospitalMölndalSweden Department of Neurodegenerative Disease UCL Institute of NeurologyQueen SquareLondonUK UK Dementia Research Institute at UCL LondonUK Hong Kong Center for Neurodegenerative Diseases Clear Water BayHong KongChina Wisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWIUSA Karolinska University Hospital StockholmSweden MedSurgPI LLCRaleighNCUSA CSD Biostatistics Inc.Oro ValleyAZUSA Aclairo Pharmaceutical Development Group IncViennaVAUSA Keck School of Medicine of USC Los AngelesCAUSA McKnight Brain Institute University of FloridaGainesvilleFLUSA Sanders-Brown Center on Aging University of KentuckyLexingtonKYUSA Global R&D Partners LLCSan DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoUSA

Trial Registration:May 11th,2018 *** Identifier:NCT03522129 https://clini caltr ***/ct2/show/*** therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet *** evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].

关键词： Alzheimer Aβ damage

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Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

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Animal Diseases 2024年第1期4卷 1-18页

作者： nicholas j.Haley juergen A.Richt Department of Microbiology and Immunology College of Graduate StudiesMidwestern UniversityGlendaleAZUSA Department of Diagnostic Medicine/Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKSUSA

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion *** diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of *** they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic *** the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in *** importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to *** underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion *** the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

关键词： Prion Bovine Spongiform Encephalopathy Chronic Wasting Disease Transmission Pathogenesis Zoonosis

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Design and synthesis of synthetic promoters for consistency of gene expression across growth phases and scale in ***

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Synthetic and Systems Biotechnology 2024年第2期9卷 330-339页

作者： Kristin V.Presnell Omar Melhem Sarah M.Coleman nicholas j.Morse Hal S.Alper McKetta Department of Chemical Engineering The University of Texas at Austin200E Dean Keeton St.Stop C0400AustinTX78712USA Institute for Cellular and Molecular Biology The University of Texas at Austin2500 Speedway AvenueAustinTX78712USA

Metabolic engineering and synthetic biology endeavors benefit from promoters that perform consistently(or robustly)with respect to cellular growth phase(exponential and stationary)and fermentation scale(microtiter plates,tubes,flasks,and bioreactors).However,nearly all endogenous promoters(especially in Saccharomyces cerevisiae)do not perform in this *** this work,a hybrid promoter engineering strategy is leveraged to create novel synthetic promoters with robustness across these *** a multi-dimensional RNA-seq dataset,promoters with specific phase dependencies were *** enriched with functional transcription factors were identified using MEME *** motif-containing fragments could impart activity dependence in the opposing ***,we obtain two new promoters with high and consistent expression across both phases by increasing the exponential phase activity of the starting stationary-phase scaffold by 38 and 23-fold ***,we show that these promoters function consistently across various laboratory growth scales over time in a microtiter plate and in ***,this work presents and validates a new strategy for engineering promoters in *** with high levels of expression that are robust to cellular growth phase and the scale of the culture.

关键词： endogenous synthetic stationary

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HDPairFinder:A data processing platform for hydrogen/deuterium isotopic labeling-based nontargeted analysis of trace-level amino-containing chemicals in environmental water

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journal of Environmental Sciences 2024年第2期136卷 583-593页

作者： Tingting Zhao Kristin Carroll Caley B.Craven nicholas j.P.Wawryk Shipei Xing jian Guo Xing-Fang Li Tao Huan Department of Chemistry Faculty of ScienceUniversity of British ColumbiaVancouver Campus2036 Main MallVancouverBritish ColumbiaV6T 1Z1Canada Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water *** the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data *** address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and ***,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled ***,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C ***,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound ***,we integrated these modules into a freely available R program,*** rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water *** further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water *** is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.

关键词： Isotope labeling Nontargeted analysis Reactive N-compounds HPLC-HRMS Source water

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Morphological traits explain the individual position within resource-consumer networks of a Neotropical marsupial

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Current Zoology 2024年第4期70卷 453-464页

作者： nicholas F.de Camargo Hernani F.M.de Oliveira juliana F.Ribeiro Amabilio j.A.de Camargo Emerson M.Vieira Laboratorio de Ecologia de Vertebrados Departamento de EcologiaInstituto de Ciencias BiologicasUniversidade de BrasiliaCP 04457BrasiliaDF70910-900Brazil Departamento de Zoologia Setor de Ciencias BiologicasUniversidade Federal do ParanaAvenida Coronel Francisco Heraclito dos Santos100CuritibaPR81531980Brazil Embrapa Cerrados Rodovia BR020km 18CP 08223PlanaltinaDE73310-970Brazil

Knowledge regarding the influence of individual traits on interaction patterns in nature can help understand the topological role of individuals within a network of intrapopulation *** tested hypotheses on the relationships between individuals'positions within networks(specialization and centrality)of 4 populations of the mouse opossum Gracilinanus agilis and their traits(i.e.,body length,body condition,tail length relative to body length,sex,reproductive condition,and botfly parasitism)and also seasonal effects in the Brazilian *** with lower body length,better body condition,and relatively shorter tail were more specialized(i.e.,less connected within the network).Individuals were also more specialized and less connected during the warm-wet *** relationship between individuals'position in the network and body traits,however,was independent of *** propose that specialization may arise not only as a result of preferred feed-ing strategies by more capable individuals(i.e.,those with better body condition and potentially prone to defend and access high-quality food resources)but alsobecause of morphological ***/younger individuals(consequently with less experience in foraging)and short-tailed individuals(less skilled to explore the vertical strata of the vegetation)would feed only on a subset of the available food resources and consequently become more ***,individuals are more specialized during the warm-wet season because of high competition(population-dense period)and higher ecological opportunities(resource-rich period).Therefore,our study reveals the relevance of individual traits inshaping interactionpatternsandspecialization inpopulations.

关键词： bodytraits centrality Cerrado Gracilinanus agilis seasonality specialization.

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Olympic Games and 24-hour movement behaviors:A match worth making

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journal of Sport and Health Science 2024年第6期13卷 728-731页

作者： Mark S.Tremblay nicholas Kuzik Markus j.Duncan Diego Augusto Santos Silva CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina FlorianopolisSanta Catarina 88040-900Brazil

*** The Olympic motto,"Faster,Higher,Stronger-Together",represents the pursuit of athletic excellence,united as a global community."Excellence,respect and friendship"are the Olympic *** the motto and values are multifaceted and holistic in nature,and all-encompassing in their reach while recognizing no single entity rises above the ***,these foundational statements anchor the Olympic movement in its quest to build a better world through sport.

关键词： movement Together pursuit

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Assembling the RNA therapeutics toolbox

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Medical Review 2024年第2期4卷 110-128页

作者： Mona Teng Ziting judy Xia nicholas Lo Kashif Daud Housheng Hansen He Department of Medical Biophysics Temerty Faculty of MedicineUniversity of TorontoTorontoONCanada Princess Margaret Cancer Centre University Health NetworkTorontoONCanada Department of Medical Biophysics Temerty Faculty of MedicineUniversity of TorontoToronto M2J 4A6ONCanada Princess Margaret Cancer Centre University Health NetworkToronto M2J 4A6ONCanada

From the approval of COVID-19 mRNA vaccines to the 2023 Nobel Prize awarded for nucleoside base modifications,RNA therapeutics have entered the spotlight and are transforming drug *** the term“RNA therapeutics”has been used in various contexts,this review focuses on treatments that utilize RNA as a component or target RNA for therapeutic *** summarize the latest advances in RNA-targeting tools and RNA-based technologies,including but not limited to mRNA,antisense oligos,siRNAs,small molecules and RNA *** focus on the mechanisms of current FDA-approved therapeutics but also provide a discussion on the upcoming *** clinical utility of RNA-based therapeutics is enabled not only by the advances in RNA technologies but in conjunction with the significant improvements in chemical modifications and delivery platforms,which are also briefly discussed in the *** summarize the latest RNA therapeutics based on their mechanisms and therapeutic effects,which include expressing proteins for vaccination and protein replacement therapies,degrading deleterious RNA,modulating transcription and translation efficiency,targeting noncoding RNAs,binding and modulating protein activity and editing RNA sequences and *** review emphasizes the concept of an RNA therapeutic toolbox,pinpointing the readers to all the tools available for their desired research and clinical *** the field advances,the catalog of RNA therapeutic tools continues to grow,further allowing researchers to combine appropriate RNA technologies with suitable chemical modifications and delivery platforms to develop therapeutics tailored to their specific clinical challenges.

关键词： RNA therapeutics delivery of nucleic acids chemical modifications

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Towards precision 24-hour movement behavior recommendations—The next new paradigm?

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journal of Sport and Health Science 2024年第6期13卷 743-748页

作者： Mark S.Tremblay Markus j.Duncan nicholas Kuzik Diego Augusto Santos Silva Valerie Carson CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina Santa Catarina 88040900Brazil Faculty of Kinesiology Sportand RecreationUniversity of AlbertaEdmontonAB T6G 2H9Canada

*** The importance of physical activity(PA)for health is unequivocal.^(1)Accordingly,population-based recommendations for exercise,and more recently public health guidelines for PA,have been developed and released by authoritative groups for many decades.^(2)Such guidelines emerged with leadership from the exercise physiology discipline and were rooted in,and loyal to,the importance of moderate-to-vigorous intensity PA(MVPA)or exercise.

关键词： movement behavior exercise

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Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani nicholas W.Markin Kim F.Duncan Michael j.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical *** models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based *** considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical *** present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical *** are also considered a potential source of organs for human heart and kidney *** is imperative to minimize animal loss during procedures that are surgically *** present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

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Toward a nomenclature consensus for diverse intelligent systems:Call for collaboration

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The Innovation 2024年第5期5卷 32-34页

作者： Brett j.Kagan Michael Mahlis Anjali Bhat josh Bongard Victor MCole Phillip Corlett Christopher Gyngell Thomas Hartung Bianca jupp Michael Levin Tamra Lysaght nicholas Opie Adeel Razi Lena Smirnova Ian Tennant Peter Thestrup Wade Ge Wang Cortical Labs BrunswickVIC 3056Australia Wellcome Centre for Human Neuroimaging University College LondonLondon WC1N 3ARUK University of Vermont BurlingtonVT 05405USA Centre for Professional Communication Singapore Institute of TechnologySingapore 138683Singapore Department of Psychiatry Yale UniversityNew HavenCT 06511USA Murdoch Children’s Research Institute ParkvilleVIC 3052Australia Centre for Alternatives to Animal Testing(CAAT) Bloomberg School of Public Health and Whiting School of EngineeringJohns Hopkins UniversityDoerenkamp-Zbinden Chair for Evidence-based ToxicologyBaltimoreMD 21205USA CAAT-Europe University of Kostanz78464 KostanzGermany Department of Neuroscience Central Clinical SchoolMonash UniversityPrahranVIC 3004Australia Allen Discovery Centre at Tufts University MedfordMA 02155USA Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Faculty of Medicine and Health Sydney School of Public Health The University of SydneyCamperdownNSW 2050Australia Department of Medicine University of MelbourneParkvilleVIC 3010Australia Turner Institute for Brain and Mental Health Monash UniversityClaytonVIC 3168Australia Center for Alternatives to Animal Testing(CAAT) Bloomberg School of Public Health and Whiting School of EngineeringJohns Hopkins UniversityBaltimoreMD 21205USA Faculty of Engineering AgriTech and EnvironmentAnglia Ruskin UniversityPeterborough PE15BWUK Interacting Minds Centre Aarhus University8000 Aarhus CDenmark Department of Biomedical Engineering School of EngineeringBiomedical Imaging CenterCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA Department of Biochemistry and Pharmacology University of MelbourneParkvilleVIC 3010Australia

Disagreements about language use are common both between and within *** interests require multidisciplinary collaboration or the field of research has the potential to impact society at large,it becomes critical to minimize these disagreements where *** development of diverse intelligent systems,regardless of the substrate(e.g.,silicon ***),is a case where both conditions are *** advancements have occurred in the development of technology progressing toward these diverse intelligence *** progress is silicon based,such as the use of large language models,or through synthetic biology methods,such as the development of organoids,a clear need for a community-based approach to seeking consensus on nomenclature is now ***,we welcome collaboration from the wider scientific community,proposing a pathway forward to achieving this intention,highlighting key terms and fields of relevance,and suggesting potential consensus-making methods to be applied.

关键词： seeking collaboration diverse

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