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Putting it all together： intrinsic and extrinsic mechanisms governing proteasome biogenesis

Frontiers in Biology 2017年第1期12卷 19-48页

作者： lauren A. Howell Robert j. Tomko jr. Andrew R. Kusmierczyk Department of Biomedical Sciences Florida State University College of Medicine Tallahassee FL 32306 USA Department of Biology Indiana University-Purdue Universi~ Indianapolis Indianapolis IN 46202 USA

BACKGROUND： The 26S proteasome is at the heart of the ubiquitin-proteasome system, which is the key cellular pathway for the regulated degradation of proteins and enforcement of protein quality control. The 26S proteasome is an unusually large and complicated protease comprising a 28-subunit core particle （CP） capped by one or two 19-subunit regulatory particles （RP）. Multiple activities within the RP process incoming ubiquitinated substrates for eventual degradation by the barrel-shaped CE The large size and elaborate architecture of the proteasome have made it an exceptional model for understanding mechanistic themes in macromolecular assembly. OBjECTIVE： In the present work, we highlight the most recent mechanistic insights into proteasome assembly, with particular emphasis on intrinsic and extrinsic factors regulating proteasome biogenesis. We also describe new and exciting questions arising about how proteasome assembly is regulated and deregulated in normal and diseased cells. METHODS： A comprehensive literature search using the PubMed search engine was performed, and key findings yielding mechanistic insight into proteasome assembly were included in this review. RESULTS： Key recent studies have revealed that proteasome biogenesis is dependent upon intrinsic features of the subunits themselves as well as extrinsic factors, many of which function as dedicated chaperones. CONCLUSION： Cells rely on a diverse set of mechanistic strategies to ensure the rapid, efficient, and faithful assembly of proteasomes from their cognate subunits. Importantly, physiological as well as pathological changes to proteasome assembly are emerging as exciting paradigms to alter protein degradation in vivo.

关键词： proteasome assembly assembly chaperones ubiquitin-proteasome system proteolysis macromolecular complex

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Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease:A paradigm shift from acid to bacteria?

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World journal of Gastroenterology 2021年第18期27卷 2054-2072页

作者： Steve M D'Souza Kevin Houston lauren Keenan Byung Soo Yoo Parth j Parekh David A johnson Department of Internal Medicine Division of GastroenterologyEastern Virginia Medical SchoolNorfolkVA 23502United States

Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and *** interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the *** relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the *** changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other *** effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease *** has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory ***,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).

关键词： Microbiome Gastroesophageal reflux disease Probiotics Prebiotics Bacteriocins Dysbiosis Barrett’s esophagus Esophageal cancer Esophagitis Eosinophilic esophagitis

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U-47700-Incidence of a Novel Psychoactive Substance in a Series of Medical Examiner Cases in Oakland County,MI

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journal of Forensic Science and Medicine 2020年第3期6卷 105-109页

作者： lauren Aiello Emily Skwarek Daniel Isenschmidt Ljubisa j.Dragovic Oakland County Medical Examiner's Office PontiacMIUSA

U-47700 is one of many drugs that have been part of a group of compounds called novel psychoactive substances(NPS).U-47700 is a synthetic opioid agonist developed by Upjohn pharmaceuticals but never *** Oakland County Medical Examiner's Office in Pontiac,Michigan,began observing this compound in the fall of 2016,primarily in cases with other drugs of abuse and *** communication described 18 drug-related deaths in which U-47700 was *** U-47700 concentrations ranged from 0.37 to 370 ng/mL(mean 35 and median 4.9 ng/mL).Other opioids were detected in 83% of the *** drugs present in these cases are described as well as the scene *** only one death was likely due directly to U-47700,the cases described here demonstrate how NPS have become an important consideration in evaluating drug-related deaths today.

关键词： Autopsy death investigation Michigan opioid overdose U-47700

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Applications of next-generation sequencing to the study of biological invasions

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Current Zoology 2015年第3期61卷 488-504页

作者： Marc RIUS Steve BOURNE Harry Guy HORNSBY Mark A. chapman Ocean and Earth Science National Oceanography Centre Southampton University of Southampton SO 14 3ZH UK Centre for Biological Sciences Life Sciences Building 85 University of Southampton Southampton SO 17 1B J UK

Through the widespread implementation of next-generation sequencing （NGS）, analyses of the whole genome （the entire DNA content） and the whole transcriptome （the genes being expressed） are becoming commonplace. NGS enables the analysis of a vast amount of previously unattainable genetic information. Despite this potential, NGS has yet to be widely imple- mented in genetic studies of biological invasions. The study of the genomic causes and consequences of biological invasions al- lows a deeper understanding of the molecular mechanisms underpinning the invasion process. In this review, we present a brief introduction to NGS followed by a synthesis of current research in the genomics and transcriptomics of adaptation and coloniza- tion. We then highlight research opportunities in the field, including：（1） assembling genomes and transcriptomes of non-model organisms, （2） identifying genomic regions and candidate genes underlying evolutionary processes, and （3） studying the adaptive role of gene expression variation. In particular, because introduced species face a broad range of physiological and biotic chal- lenges when colonizing novel and variable environments, transcriptomics will enable the study of gene regulatory pathways that may be responsible for acclimation or adaptation. To conclude, we identify a number of research approaches that will aid our fu- ture understanding of biological invasions

关键词： Exotic species Genomics Genotype-environment interactions Invasive species Invasion genetics Invasion route Non-indigenous species Non-native species

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Revisiting the conversion reaction voltage and the reversibility of the CuF2 electrode in Li-ion batteries

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Nano Research 2017年第12期10卷 4232-4244页

作者： joon Kyo Seo Hyung-Man Cho Katsunori Takahara Karena W. chapman Olaf j. Borkiewicz Mahsa Sina Y. Shirley Meng Department of NanoEngineering University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA Materials Science and Engineering University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA X-ray Science Division Advanced Photon Source Argonne National Laboratory 9700 South Cass Avenue Argonne IL 60439 USA

Deviation between thermodynamic and experimental voltages is one of the key issues in Li-ion conversion-type electrode materials; the factor that affects this phenomenon has not been understood well in spite of its importance. In this work, we combine first principles calculations and electrochemical experiments with characterization tools to probe the conversion reaction voltage of transition metal difluorides MF2（M = Fe, Ni, and Cu）. We find that the conversion reaction voltage is heavily dependent on the size of the metal nanoparticles generated. The surface energy of metal nanoparticles appears to penalize the reaction energy, which results in a lower voltage compared to the thermodynamic voltage of a bulk-phase reaction. Furthermore, we develop a reversible CuF2 electrode coated with NiO. Electron energy loss spectroscopy （EELS） elemental maps demonstrate that the lithiation process mostly occurs in the area of high NiO content. This suggests that NiO can be considered a suitable artificial solid electrolyte interphase that prevents direct contact between Cu nanoparticles and the electrolyte. Thus, it alleviates Cu dissolution into the electrolyte and improves the reversibility of CuF2.

关键词： Li-ion battery conversion material reaction voltage nanoparticle reversibility coating

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Ultrastructure of the gastro intestinal tract of healthy japanese quail(Coturnix japonica) using light and scanning electron microscopy

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Animal Nutrition 2018年第4期4卷 378-387页

作者： Ngare Wilkinson Ivan Dinev William j.Aspden Robert j.Hughes Ingrid Christiansen james chapman Sheeana Gangadoo Robert j.Moore Dragana Stanley Central Queensland University Institute for Future Farming Systems Poultry Cooperative Research Centre University of New England Armidale Faculty of Veterinary Medicine Trakia University South Australian Research and Development Institute Pig and Poultry Production Institute School of Animal and Veterinary Sciences University of Adelaide School of Science RMIT University Department of Microbiology Monash University

The japanese quail(Coturnix japonica) are popular both as an alternative protein source and as a model of choice for scientific research in several disciplines. There is limited published information on the histological features of the intestinal tract of japanese quail. The only comprehensive reference is a book published in 1969. This study aims to fill that niche by providing a reference of general histological features of the japanese quail, covering all the main sections of the intestinal tract. Both light and scanning electron microscope(SEM) images are presented. Results showed that the japanese quail intestinal tract is very similar to that of the chicken with the exception of the luminal koilin membrane of the gizzard. Scanning electron microscopic photomicrographs show that in the japanese quail koilin vertical rods are tightly packed together in a uniform manner making a carpet-like appearance. This differs in chicken where the conformations of vertical rods are arranged in clusters.

关键词： japanese quail Coturnix japonica Histology Microscopy Scanning electron microscopy Gastrointestinal tract

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The association between sexual function and prostate cancer risk in US veterans

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Asian journal of Andrology 2017年第2期19卷 191-195页

作者： Daniel F Zapata lauren E Howard jennifer Frank Ross M Simon Cathrine Hoyo Delores j Grant Stephen j Freedland Adriana C Vidal Duke University Medical Center Division of Urology Department of Surgery Durham NC 27710 USA Durham Veterans Affairs Medical Center Urology Division Durham NC 27710 USA North Carolina State University Department of Biology Raleigh NC 27695 USA North Carolina Central University Department of Biology Durham NC 27707 USA Department of Surgery Division of Urology Samuel Oschin Comprehensive Cancer institute Cedars-Sinai Medical Center Los Angeles California 90048 USA

Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men. Among 448 men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, sexual function was ascertained from the Expanded Prostate Cancer Index Composite sexual assessment. We tested the link between sexual function and prostate cancer risk adjusting for multiple demographic and clinical characteristics using logistic regression. Multinomial logistic regression was used to test the associations with risk of low-grade （Gleason 〈6） and high-grade （Gleason 〉7 or 〉4 ＋ 3） disease versus no cancer. Of 448 men, 209 （47%） had a positive biopsy; these men were less likely to be white （43% vs 55%, P=0.013）, had higher prostate-specific antigen （PSA）（6.0 vs 5.4 ng ml-1, P 〈 0.001）, but with lower mean sexual function score （47 vs 54, P = 0.007）. There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. After adjusting for baseline differences, sexual function was linked with a decreased risk of overall prostate cancer risk （OR. 0.91 per lO-point change in sexual function, P= 0.004） and high-grade disease whether defined as Gleason ≥7 （OR： 0.86, P= 0.001） or 〉4 ＋ 3 （OR： 0.85, P= 0.009）. Sexual function was unrelated to low-grade prostate cancer （OR： 0.94, P = 0.13）. Thus, among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade prostate cancer. Confirmatory studies are needed.

关键词： erectile dysfunction prostate prostate cancer risk sexual function

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Underlying solvent-based factors that influence permanent porosity in porous liquids

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Nano Research 2022年第4期15卷 3533-3538页

作者： Hamidreza Mahdavi Huacheng Zhang lauren K.Macreadie Cara M.Doherty Durga Acharya Stefan j.DSmith Xavier Mulet Matthew R.Hill Department of Chemical Engineering Monash UniversityClaytonVIC 3800Australia CSIRO Manufacturing Private Bag 10Clayton SouthVIC 3169Australia School of Chemistry University of SydneySydney 2006Australia

Porous liquids(PLs)offer the potential to combine the ready handling and mature industry status of liquid absorbents,with the high permanent porosity of metal organic *** be functional,these nanocomposites need to satisfy a number of performance parameters,such as stability and viscosity of the porogen-solvent combination,avoiding solvent penetration into metal organic framework(MOF)pores,suitable capacities,and kinetics for gas *** this work,we systematically investigate the component materials to elucidate the parametric space where stable photoluminescence(PL)can be *** this situation,deeper conclusions were able to be drawn with regard to the influence of hydrophobicity/philicity on the properties of the resulting *** imidazolate frameworks(ZIFs)were combined with a range of solvents varying in steric bulk,to deliver CO_(2)sorption capacities as high as 4.2 mmol·g^(-1)at 10 *** findings may have broader implications for future investigations of this tantalising field of nanocomposites.

关键词： zeolitic imidazolate frameworks porous liquids permanent porosity gas sorption

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Novel data-driven subtypes and stages of brain atrophy in the ALS-FTD spectrum

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Translational Neurodegeneration 2023年第1期12卷 50-69页

作者： Ting Shen jacob W.Vogel jeffrey Duda jeffrey S.Phillips Philip ACook james Gee lauren Elman Colin Quinn Defne A.Amado Michael Baer lauren Massimo Murray Grossman David j.Irwin Corey T.McMillan Penn Frontotemporal Degeneration Center Department of NeurologyPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Clinical Sciences SciLifeLabLund University22242 LundSweden Penn Image Computing and Science Lab(PICSL) Department of RadiologyPerelman School of MedicineUniversity of Penn-sylvaniaPhiladelphiaPA 19104USA Department of Neurology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Digital Neuropathology Laboratory Department of NeurologyPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA.

Background TDP-43 proteinopathies represent a spectrum of neurological disorders,anchored clinically on either end by amyotrophic lateral sclerosis(ALS)and frontotemporal degeneration(FTD).The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes,highlighting its *** study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD *** We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD(bvFTD;with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants),103 ALS,and 47 ALS-FTD patients with likely TDP-43.A Subtype and Stage Inference(SuStaIn)model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns,and we related subtypes and stages to clinical,genetic,and neuropathological features of *** SuStaIn identified three novel subtypes:two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions,and a normal-appearing group without obvious brain *** limbic-predominant subtype tended to present with more impaired cognition,higher frequencies of pathogenic variants in TBK1 and TARDBP genes,and a higher proportion of TDP-43 types B,E and *** contrast,the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type *** normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients,higher cognitive capacity,higher proportion of lower motor neuron onset,milder motor symptoms,and lower frequencies of genetic pathogenic *** overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration,higher King’s stage,and cog

关键词： Amyotrophic lateral sclerosis Frontotemporal degeneration Disease heterogeneity SuStaIn model

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Angina rapidly improved with a plant-based diet and returned after resuming a Western diet

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journal of Geriatric Cardiology 2016年第4期13卷 364-366页

作者： Daniele Massera lauren Graf Sofia Barba Robert Ostfeld Department of Medicine Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine Bronx NY USA Stevens lnstimte of Technology Hoboken N J USA

Atherosclerosis and its related cardiovascular disease is the most common cause of morbidity and mortality in the Western world. The roots of this disease may lie, in part, in dietary and lifestyle behaviors, indicati... 详细信息

关键词： Cardiovascular disease Lifestyle therapy Nutrition Plant-based diet

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