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Neural Regeneration Research 2020年第1期15卷 69-70页

作者： nicole Zarate Rocio Gomez-Pastor Department of Neuroscience School of Medicine University of Minnesota

Heat shock factor 1(HSF1)is abnormally degraded in Huntington’s disease(HD):HD is a neurodegenerative disorder characterized by severe cognitive and motor *** is caused by a CAG repeat expansion within exon 1 of the huntingtin(HTT)gene(The Huntington’s Disease Collaborative Research Group,1993).These expansions lead to the production of an aberrant mutant huntingtin protein(mHTT)that is prone to misfolding and *** and aggregation of mHTT is present in virtually all cell types in the body but preferentially affects medium spiny neurons of the striatum,a brain region that controls movement and some forms of *** of mHTT leads to,but not only,transcriptional dysregulation,DNA damage,mitochondrial dysfunction and excitatory synaptic failure ultimately causing neuronal ***,the molecular mechanisms by which mHTT exerts these defects are still unclear.

关键词： Huntington impairment shock

LiDAR mapping of ground damage in a heading re-orientation case study

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International Journal of Mining Science and Technology 2021年第1期31卷 67-74页

作者： nicole Evanek Brent Slaker Anthony Iannacchione Tim Miller National Institute for Occupational Safety and Health Pittsburgh Mining Research DivisionPittsburghPA 15236USA University of Pittsburgh PittsburghPA 15260USA East Fairfield Coal Company North LimaOH 44452USA

The Subtropolis Mine is a room-and-pillar mine extracting the Vanport limestone near Petersburg,Ohio,*** February of 2018,mine management began implementing a heading re-orientation to better control the negative effects of excessive levels of horizontal *** conditions in the headings improved,but as expected,stress-related damage concentrated within *** mine operator has worked to lessen the impact of the instabilities in the outby crosscuts by implementing several engineering *** the implementation of each control,conditions were monitored and analyzed using observational and measurement techniques including 3D LiDAR *** the heading re-orientation,several 3D LiDAR surveys have been conducted and analyzed by researchers from the National Institute for Occupational Safety and Health(NIOSH).This study examines(1)the characteristics of each 3D LiDAR survey,(2)the change in the detailed strata conditions in response to stress concentrations,and(3)the change detection techniques between 3D LiDAR surveys to assess entry ***,the 3D LiDAR surveys proved to be a useful tool for characterizing ground instability and assessing the effectiveness of the engineering controls used in the heading re-orientation at the Subtropolis Mine.

关键词： Ground control Limestone Horizontal stress Stress control layout Crosscut Windows

Acetylation of PPARγin macrophages promotes visceral fat degeneration in obesity

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Life Metabolism 2022年第3期1卷 258-269页

作者： nicole Aaron Tarik Zahr Ying He Lexiang Yu Brent Mayfield Utpal BPajvani Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNYUSA Department of Pharmacology Columbia UniversityNew YorkNYUSA Department of Pathology and Cell Biology Columbia UniversityNew YorkNYUSA Department of Genetics and Development Columbia UniversityNew YorkNYUSA Department of Medicine Columbia UniversityNew YorkNYUSA

Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose ***γ is well established to have an anti-inflammatory function in macrophages,but the mechanism that regulates its function in these cells remains to be fully ***γundergoes post-translational modifications(PTMs),including acetylation,to mediate ligand responses,including on metabolic ***,we report that PPARγacetylation in macrophages promotes their infiltration into adipose tissue,exacerbating metabolic *** generated a mouse line that expresses a macrophage-specific,constitutive acetylation-mimetic form of PPARγ(K293Q^(flox/flox):LysM-cre,mK293Q)to dissect the role of PPARγacetylation in *** highfat diet feeding to stimulate macrophage infiltration into adipose tissue,we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice,including responses to the PPARγagonist ***-specific PPARγK293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue,but not in subcutaneous or brown adipose tissue,leading to decreased energy expenditure,insulin sensitivity,glucose tolerance,and adipose tissue ***,mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue *** study reveals that acetylation is a new layer of PPARγregulation in macrophage activation,and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.

关键词： PPARγacetylation adipose tissue remodeling macrophage inflammation fibrosis

Model-based evaluation of policy impacts and the continued COVID-19 risk at long term care facilities

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Infectious Disease Modelling 2022年第3期7卷 463-472页

作者： Bailey K.Fosdick Jude Bayham Jake Dilliott Gregory D.Ebel nicole Ehrhart Department of Statistics Colorado State UniversityFt.CollinsCO80523USA Department of Agricultural and Resource Economics Colorado State UniversityFt.CollinsCO80523USA Arthropod-Borne and Infectious Diseases Laboratory Department of MicrobiologyImmunology and PathologyColorado State UniversityFt.CollinsCO80526USA Columbine Health Systems Center for Healthy Aging and Department of Clinical Sciences Colorado State UniversityFt.CollinsCO80523USA

The COVID-19 pandemic severely impacted long-term care facilities resulting in the death of approximately 8%of residents nationwide as of March *** COVID-19 case rates declined and state and county restrictions were lifted in spring 2021,facility managers,local and state health agencies were challenged with defining their own policies moving forward to appropriately mitigate disease *** continued emergence of variants of concern and variable vaccineuptake across facilitieshighlighted the need for a readily available tool that can beemployed at the facility-level to determine best practices for mitigation and ensure resident and staff *** assist leadership in determining the impact of various infection surveillance and response strategies,we developed an agent-based model and an online dashboard interface that simulates COVID-19 infection within congregate care settings under various mitigation *** dashboard quantifies the continued risk for COVID-19 infections within a facility given a designated testing schedule and vaccine *** findings were that choice of COVID-19 diagnostic(*** swab qRT-PCR vs rapid antigen)and testing cadence has less impact on attack rate and staff workdays missed than does vaccination rates among staff and ***,low vaccine uptake among staff at long-term care facilities puts staff and residents at risk of ongoing COVID-19 *** we present our model and dashboard as an exemplar of a tool for state public health officials and facility directors to gain insights from an infectious disease model that can directly inform policy decisions in the midst of a pandemic.

关键词： Agent-based model Nonpharmaceutical interventions Vaccine uptake COVID-19

Presentations,treatment and outcomes of unifocal and multifocal osseous appendicular Langerhans cell histiocytosis lesions in a pediatric population

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World Journal of Pediatric Surgery 2023年第1期6卷 55-57页

作者： Ekene U Ezeokoli Parker Mitchell Eva Schlehr Neritan Borici nicole Montgomery Department of Orthopedic Surgery Texas Children's HospitalHoustonTexasUSA Oakland University William Beaumont School of Medicine RochesterMichiganUSA Department of Orthopedic Surgery Baylor College of MedicineHoustonTexasUSA Baylor College of Medicine HoustonTexasUSA University at Buffalo Jacobs School of Medicine and Biomedical Sciences BuffaloNew YorkUSA

Langerhans cell histiocytosis(LCH)is a rare disease most commonly presenting in the pediatric population and characterized by neoplastic clonal proliferation of Langerhans dendritic cells with accumulation in various sites,including skeletal and visceral lesions.1 There are three levels of classification per the Histiocyte Society:single-system single-site(SS-s),single-system multiple-site(SS-m),and multisystem(MS).2 SS-s predominantly carries a better prognosis with more conservative treatment while MS requires a more aggressive treatment that is more likely to have an inferior outcome.

关键词： Langerhans lesions treatment

Plant peroxisomal solute transporter proteins

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Journal of Integrative Plant Biology 2019年第7期61卷 817-835页

作者： Lennart Charton Anastasija Plett nicole Linka Institute for Plant Biochemistry and Cluster of Excellence on Plant Sciences (CEPLAS) Heinrich Heine University

Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid b-oxidation,photorespiration, and degradation of reactive oxygen species. The compartmentalization of metabolic pathways into peroxisomes is a strategy for organizing the metabolic network and improving pathway efficiency. An important prerequisite, however, is the exchange of metabolites between peroxisomes and other cell compartments. Since the first studies in the 1970s scientists contributed to understanding how solutes enter or leave this *** review gives an overview about our current knowledge of the solute permeability of peroxisomal membranes described in plants, yeast, mammals and other eukaryotes. In general, peroxisomes contain in their bilayer membrane specific transporters for hydrophobic fatty acids(ABC transporter) and large cofactor molecules(carrier for ATP, NAD and CoA). Smaller solutes with molecular masses below 300–400 Da, like the organic acids malate, oxaloacetate, and 2-oxoglutarate, are shuttled via non-selective channels across the peroxisomal *** comparison to yeast, human, mammals and other eukaryotes, the function of these known peroxisomal transporters and channels in plants are discussed in this review.

关键词： Plant peroxisomal solute transporter proteins

Intracellular Metabolite Transporters in Plants

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Molecular Plant 2010年第1期3卷 21-53页

作者： nicole Linka Andreas RM. Weber Institute of Plant Biochemistry Heinrich-Heine Universit~t D0sseldorf Geb. 26.03.01 Universitsstsstrasse 1 40225 Dasseldorf Germany

Due to the presence of plastids, eukaryotic photosynthetic cells represent the most highly compartmentalized eukaryotic cells. This high degree of compartmentation requires the transport of solutes across intracellular membrane systems by specific membrane transporters. In this review, we summarize the recent progress on functionally characterized intracellular plant membrane transporters and we link transporter functions to Arabidopsis gene identifiers and to the transporter classification system. In addition, we outline challenges in further elucidating the plant membrane permeome and we provide an outline of novel approaches for the functional characterization of membrane transporters.

关键词： Membrane biochemistry molecular transport transporters membrane proteins.

Embolic protection device, the next advancement in TAVR?

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Journal of Geriatric Cardiology 2020年第3期17卷 160-163页

作者： David Li nicole Shirakawa Hong Liu Department of Anesthesiology and Pain Medicine University of California Davis HealthSacramentoCAUSA

The approval of commercial application transcatheter aortic valve replacement(TAVR)by the FDA in 2011 has revolutionized the management of high-risk surgical patients with severe aortic stenosis(AS).With TAVR being expanded to intermediate surgical risk patients in 2016,the number of patients undergoing TAVR has been increasing *** fact,since the very first human TAVR procedure in 2002,more than 300,000 TAVRs have been performed worldwide.[1,2]The technological advancements in the TAVR since its early days of clinical adaptation has made this procedure a routine practice in many institutions ***,one of the most feared complications,ischemic stroke,remains a major concern for clinicians and patients despite all the advancements in the procedure.

关键词： Embolic protection Stroke Transcatheter aortic valve replacement

Is the clinical head impulse test helpful in cochlear implantation candidacy evaluation?

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第1期9卷 45-52页

作者： nicole T.Jiam Yi Cai Katherine C.Wai Colleen Polite Kurt Kramer Jeffrey D.Sharon Department of Otolaryngology-Head and Neck Surgery University of California San Francisco School of MedicineSan FranciscoCaliforniaUSA

Objective:Vestibular dysfunction is a known risk of cochlear implantation(CI).However,the utility of the physical exam to screen CI candidates for vestibular dysfunction is not *** objective of this study is to evaluate the preoperative role of the clinical head impulse test(cHIT)in subjects undergoing CI surgery *** Design Setting,and Subjects:We conducted a retrospective review of 64 adult CI candidacy cases between 2017 and 2020 at a tertiary health care ***:All patients underwent audiometric testing and evaluation by the senior *** with an abnormal catch-up saccade contralateral to their worse hearing ear during cHIT were referred for formal vestibular *** included clinical and formal vestibular results,operated ear with regard to audiometric and vestibular results,and postoperative ***:Among all CI candidates,44%(n=28)reported preoperative disequilibrium ***,62%(n=40)of the cHITs were normal,33%(n=21)were abnormal,and 5%(n=3)were *** was one patient who presented with a false positive *** the patients who endorsed disequilibrium,43%had a positive preoperative *** percent of the subjects(n=9)without disequilibrium had an abnormal *** this cohort,bilateral vestibular impairment(71%)was more common than unilateral vestibular impairment(29%).In 3%of the cases(n=2),surgical management was revisited or altered due to cHIT ***:There is a high prevalence of vestibular hypofunction in the CI candidate ***-reported assessments of vestibular function are often not congruent with cHIT *** should consider incorporating cHITs as part of the preoperative physical exam to potentially avoid bilateral vestibular dysfunction in a minority of patients.

关键词： clinical head impulse test cochlear implant vestibular function vestibular loss vestibular testing

Mouse modelling of the MDM2/MDMX-p53 signalling axis

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Journal of Molecular Cell Biology 2017年第1期9卷 34-44页

作者： nicole R. Tackmann Yanping Zhang Department of Radiation Oncology Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill NC 27514 USA Curriculum in Genetics and MoLecular Biology School of Medicine University of North Carolina at Chapel HiLl Chapel HILL NC 27514 USA Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer Institute Xuzhou Medical College Xuzhou 221002 China

It is evident that p53 activity is critical for tumour prevention and stress response through its transcriptional activation of genes affecting cellular senescence, apoptosis, cellular metabolism, and DNA repair. The regulation of p53 is highly complex, and MDM2 and MDMX are thought to be critical for deciding the fate of p53, both through inhibitory binding and post-translational modification. Many mouse models have been generated to study the regulation of p53 in vivo, and they have altered our interpretations of how p53 is regulated by MDM2 and MDMX. Although MDM2 is absolutely required for p53 regulation, certain functions are dispensable under unstressed conditions, including the ability of MDM2 to degrade p53. MDMX, on the other hand, may only be required in select situations, like embryogenesis. These models have also clarified how cellular stress signals modify the p53-inhibiting activities of MDM2 and MDMX in vivo. It is clear that more work will need to be performed to further understand the contexts for each of these signals and the requirements of various MDM2 and MDMX functions. Here, we will discuss what we have learned from mouse modelling of MDM2 and MDMX and underscore the ways in which these models could inform future therapies.

关键词： E3 ubiquitin ligase MDM2 MDMX cancer p53