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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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Invasion syndromes:hypotheses on relationships among invasive species attributes and characteristics of invaded sites

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Journal of Arid Land 2013年第3期5卷 275-283页

作者： lora B PERKINS Robert S NOWAK Department of Natural Resource Management South Dakota State UniversityBrookings SD 57007USA Department of Natural Resources & Environmental Science University of NevadaReno NV 89557USA

As invasion science accepts that there is no single causal factor for biological invasion, the identification of groups of traits that are often associated, or ＂syndromes＂, is a logical move forward. Invasion syndromes are proposed to identify suites of site conditions （biotic and environmental） that render a site vulnerable to invasion by different types of invaders. This paper proposed four invasion syndromes which relate invader attributes （competitive ability, niche construction, phenotypic plasticity, and phenological niche separation） to the biotic characteristics （biodiversity and enemies） and environmental conditions （resource abundance and fluctuation） of invaded sites. The four invasion syndromes described in this paper are a development of hypotheses of how the many factors that influence species invasion might be associated. Invasion Syndrome 1 proposes that sites with relatively high resource abundance and high diversity should be vulnerable to invasion by species with high competitive ability. Invasion Syndrome 2 hypothesizes that sites with relatively low resource abundance and low diversity should be vulnerable to invasion by species with niche construction ability. Invasion Syndrome 3 postulates that sites with moderate or fluctuating resources and moderate diversity should be vulnerable to invasion by species with high phenotypic plasticity. Invasion Syndrome 4 hypothesizes that species introduced into a site where it has phenological niche separation from natives will not have to contend with interference from the biotic community at a site （diversity or natural enemies） and may invade where ever site environmental conditions suit its life history. Further work is needed to support, contradict, or refine these hypotheses and almost certainly will identify more invasion syndromes.

关键词： non-native competitive ability niche construction ecosystem engineering phenotypic plasticity phenological niche separation

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Inorganic arsenic： A non-genotoxic carcinogen

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Journal of Environmental Sciences 2016年第11期28卷 28-37页

作者： Samuel M.Cohen Aparajita Chowdhury lora L.Arnold Department of Pathology and Microbiology University of Nebraska Medical Center Omaha NE 68198-3135 USA.

Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.

关键词： Arsenic Cancer Genotoxicity Cytotoxicity Regeneration Cell proliferation

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Studying Formability Limits By Combining Conventional and Incremental Sheet Forming Process

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Chinese Journal of Mechanical Engineering 2021年第4期34卷 78-89页

作者： Fabio Andre lora Daniel Fritzen Ricardo Alves de Sousa Lirio Schaffer Department of Materials Engineering Federal University of Recôncavo da BahiaCampus CETENSFeira de SantanaBahia 44085-132Brazil SATC Uni-versity CriciumaBrazil Center of Mechanical Technology and Automation Department of Mechanical EngineeringUniversity of Aveiro3810-193 AveiroPortugal Federal University of Rio Grande do Sul Porto AlegreBrazil

In this work it is assessed the potential of combining conventional and incremental sheet forming processes in a same sheet of *** so-called hybrid forming approach is performed through the manufacture of a pre-forming by conventional forming,followed by incremental sheet *** main objective is analyzing strain *** pre-forming induced in the conventional forming stage will determine the strain paths,directly influencing the strains produced by the incremental *** conduct the study,in the conventional processes,strains were imposed in three different ways with distinct true *** the incremental stage,the pyramid strategy was adopted with different wall *** the experiments,the true strains and the final geometries were *** simulation was also employed for the sake of comparison and correlation with the measured *** could be observed that single-stretch pre-strain was directly proportional to the maximum incremental strains achieved,whereas samples subjected to biaxial pre-strain influenced the formability according to the degree of pre-strain ***-strain driven by the prior deep-drawing operation did not result,in this particular geometry,in increased formability.

关键词： Hybrid forming process Incremental sheet forming Strain paths Numerical simulation

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Management of psoriasis patients with hepatitis B or hepatitis C virus infection

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World Journal of Gastroenterology 2016年第28期22卷 6444-6455页

作者： Claudio Bonifati Viviana lora Dario Graceffa Lorenzo Nosotti Center for the Study and Treatment of Psoriasis San Gallicano Dermatologic Institute IRCCS Gastrointestinal and Liver Department National Institute for Health Migration and Poverty

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be

关键词： Psoriasis Therapy Conventional disease-modifying drugs Biological disease-modifying drugs Hepatitis B virus infection Hepatitis C virus infection

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Progesterone modulates m TOR in the hippocampus of mice after traumatic brain injury

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Neural Regeneration Research 2018年第3期13卷 434-439页

作者： Richard Justin Garling lora Talley Watts Shane Sprague Murat Digicaylioglu Department of Neurosurgery Wayne State University Detroit MI USA School of Medicine The University of Texas Health Science Center at San Antonio San Antonio TX USA Department of Neurosurgery The University of Texas Health Science Center at San Antonio San Antonio TX USA

Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental *** days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells （regenerating nerve fibers） and less glial fibrillary acidic protein-immunoreactive cells （astrocytic scar tissue） were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue,and as such, is more suitable to help the repair of spinal cord injury.

关键词： nerve regeneration spinal cord injury chitosan sodium alginate functional recovery scaffold neurofilament-H glial fibrillary acidic protein scar tissue locomotor capacity neural regeneration

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Invasive grasses consistently create similar plant-soil feedback types in soils collected from geographically distant locations

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Journal of Plant Ecology 2016年第2期9卷 180-186页

作者： lora B.Perkins Gary Hatfield Erin K.Espeland Department of Natural Resource Management South Dakota State University1 N.Campus Dr.BrookingsSD 57007USA Department of Mathematics and Statistics South Dakota State University100 Admin LaneBrookingsSD 57007USA Pest Management Research Unit USDA-ARS NPARL1500 North Central AveSidneyMT 59270USA

Aims Plants of similar life forms and closely related species have been observed to create similar types of plant–soil feedbacks(PSFs).However,investigations of the consistency of PSFs within species have not yielded clear *** example,it has been reported that species create different types of PSFs in their native and introduced *** aim of this project is to examine if four species create similar PSF types from soils collected from widely distributed areas within their introduced *** soil for this project was collected from three areas in western North *** this design,we aim to determine species-and site-specific ability to create PSFs and if the type of PSF created is consistent in all soil from all three collection *** species examined are Agropyron cristatum,Centaurea solstitialis,Poa pratensis and Taeniatherum *** We used three-field collected soils(from northern Nevada,western Montana and eastern Montana)in a two-phase greenhouse experiment to quantify the type of PSFs created by four invasive *** first phase was a conditioning phase wherein each invasive species created species-specific changes to the *** second phase of the experiment was the response phase wherein both the conditioning species and a native phytometer were grown in the conditioned soil and in unconditioned(control)*** final aboveground biomass was used to evaluate the effect of conditioning and to determine the type of PSF created by each invasive *** Findings Our results suggest that three of our four study species did show consistency in relation to *** species *** and *** consistently created PSF types that benefit conspecifics more than heterospecifics(and thus are‘invasive’PSF types)and *** consistently exhibited no,or‘neutral’,*** fourth species(***)was inconsistent:in one soil,no feedback was created;in other soil,an invasive PSF was created and in t

关键词： plant-soil feedback invasion niche construction

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Mode of action for inorganic arsenic toxicity and carcinogenesis

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Chinese Science Bulletin 2014年第11期59卷 1078-1082页

作者： Puttappa R.Dodmane lora L.Arnold Samuel M.Cohen Department of Pathology and Microbiology University of Nebraska Medical Center983135 Nebraska Medical Center

Inorganic arsenic(iAs) at high doses is a known human carcinogen, inducing tumors of the skin,urinary bladder, and lung. It is also associated with noncancer toxicities. An understanding of the mode of action(MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models,and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity([0.1 lmol/L trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm(1 ppm = 1 mg/L) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, noncancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs.

关键词：体外细胞毒性致癌作用无机砷诱导效应会计准则氧化锌避雷器上皮组织动脉粥样硬化

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A revised generic classification of the jelly lichens, Collemataceae

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Fungal Diversity 2014年第1期64卷 275-293页

作者： Mónica A.G.Otálora Per M.Jørgensen Mats Wedin Department of Botany Swedish Museum of Natural HistoryP.O.Box 50007SE-10405 StockholmSweden Department of Natural History Bergen University MuseumAllégt.41Box 78005020 BergenNorway

Phylogenetic studies have shown the need for a revised circumscription of generic boundaries in the jelly lichens(Collemataceae).Using a four-marker dataset from a recently published phylogeny of Collemataceae,we tested the monophyly of ten morphologically well-characterized *** achieve this,we performed Bayesian and maximum likelihood *** monophyly of the ten morphological groups was *** order to reconcile molecular and morphological data into a formal classification,we here propose new generic delimitations in *** and Leptogium are re-circumscribed and six old generic names are resurrected to accommodate the Collema Crispum-group(Blennothallia),the Collema Tenax-group(Enchylium),the Collema Cristatum-group(Lathagrium),the Collema Occultatum-group(Rostania),the former small Leptogium species(Scytinium),and Leptogium diffractum(Pseudoleptogium).In addition,two new genera are described to accommodate Collema multipartitum(Callome)and the Collema Italicum-group(Paracollema).The presence/absence of a eucortex,which was earlier used as the cardinal character to define genera in the family,is still useful,but only in combination with other traits such as thallus habit(size),lobe size,ascospore characteristics,thallus anatomical structure,and habitat preference.A key to the genera is *** are designated for Collema marginale Hoffm.,Synechoblastus nigrescens(Huds.)Trevis.,Eucollema(Cromb.)Horw.,Collema section Enchylium Ach.,Collema section Lathagrium Ach.,Collema *** Ach.,Collema section Scytinium Ach.,Collemodium *** Lamy,and Homodium *** Olivier.

关键词： Classification Collemataceae Cyanolichens Jelly lichens Test of monophyly

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Stimulating mitochondria to protect the brain following traumatic brain injury

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Neural Regeneration Research 2016年第9期11卷 1403-1404页

作者： lora Talley Watts Department of Cell Systems & Anatomy Research Imaging InstituteDepartment of NeurologyUniversity of Texas Health Science Center

Traumatic brain injury （TBI） is an acquired injury to the brain that occurs with sudden trauma that can range from mild （concussive） to severe. TBI is considered a leading cause of death in children and young adults, with the Centers for Disease Control and Prevention estimating that approximately 1.7 million cases of TBI occur in the United States annually （Faul et al., 2010）. Further, since the begin- ning of the global war on terrorism, the Department of Defense has reported over 344,000 U.S. Service Members have been diagnosed with traumatic brain injury from penetrating injuries to mild forms of TBI. TBI, caused by a sudden impact, penetration, or rapid move- ment of the brain, interrupts the normal functioning of the brain. While the intracranial location and severity of injury contribute to the extent of functional deficits.

关键词： TBI Stimulating mitochondria to protect the brain following traumatic brain injury

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