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An Integrated Systems Biology Approach Identifies ZIKV and DENV Replication

Genomics, Proteomics & Bioinformatics 2021年第1期19卷 108-122页

作者： Guang Song emily m.lee Jianbo Pan miao Xu Hee-Sool Rho Yichen Cheng Nadia Whitt Shu Yang Jennifer Kouznetsova Carleen Klumpp-Thomas Samuel G.michael Cedric moore Ki-Jun Yoon Kimberly m.Christian Anton Simeonov Wenwei Huang menghang Xia Ruili Huang madhu Lal-Nag Hengli Tang Wei Zheng Jiang Qian Hongjun Song Guo-li ming Heng Zhu Department of Pharmacology&molecular Sciences Johns Hopkins School of MedicineBaltimoreMD 21205USA Department of Biological Science Florida State UniversityTallahasseeFL 32306USA Department of Ophthalmology Johns Hopkins School of MedicineBaltimoreMD 21205USA National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310016China Institute for Cell Engineering Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Neuroscience and mahoney Institute for Neurosciences Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Cell and Developmental Biology Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Regenerative medicine Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Epigenetics Institute Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease *** we employed three independent systems biology approaches toward this ***,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome ***,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this ***,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV *** analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV *** study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.

关键词： Protein–protein interaction RNAi screening Chemical genetics screening multi-omics

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Altered physiology of gastrointestinal vagal afferents following neurotrauma

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Neural Regeneration Research 2021年第2期16卷 254-263页

作者： emily N.Blanke Gregory m.Holmes emily m.Besecker Department of Health Sciences Gettysburg CollegeGettysburgPAUSA Department of Neural and Behavioral Sciences Penn State University College of MedicineHersheyPAUSA

The adaptability of the central nervous system has been revealed in several model *** particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of *** both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically ***,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal *** gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord *** the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal *** sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

关键词： gastrointestinal functions microbiome neurotrauma nodose ganglia sensory neuropathy spinal cord injury traumatic brain injury vagal afferents visceral reflexes

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Stem cell heterogeneity and regenerative competence:the enormous potential of rare cells

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Neural Regeneration Research 2021年第2期16卷 285-286页

作者： emily A.B.Gilbert Cindi m.morshead Terrence Donnelly Centre for Cellular and Biomolecular Research Division of AnatomyDepartment of SurgeryUniversity of TorontoTorontoONCanada Institute of Biomedical and Biochemical Engineering Institute of Medical ScienceUniversity of TorontoKITEToronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Reconstitution of complex multi-tissue organs is one of the most impressive feats of biology and is observed across regeneration-competent vertebrate species,including teleost fish(e.g.,zebrafish),urodeles(e.g.,axolotls and newts),and some *** ability within these species ranges from muscle(including cardiac),skeletal structures,to complex systems such as the brain,spinal cord and parts of the eye which are all capable of structural and functional repair following injury(Tanaka and Ferretti,2009).In stark contrast,re-establishment of multi-tissue structures is very rarely observed following embryogenesis in regeneration-incompetent *** of digit tips is the most dramatic example of mammalian regeneration,but pales in comparison to other species in the animal ***,a complete recapitulation of complex organs or structures in mammals will remain out of reach for a considerable time;however,an improved understanding of regenerat i ve mechanisms would likely enhance the development of novel regenerative medicine *** we focus on the diversity and commonalities of stem cells,which could underlie complex tissue regeneration.

关键词： organs rare potential

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A multicriteria Decision Analytic Approach to Systems Resilience

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International Journal of Disaster Risk Science 2024年第5期15卷 657-672页

作者： Jeff rey m.Keisler emily m.Wells Igor Linkov University of massachusetts Boston US Army Engineer Research and Development Center University of Florida

This article develops a novel decision-oriented framework that strategically deconstructs systems resilience in a way that focuses on systems' design, capabilities, and management. The framework helps evaluate and compare how system design choices impact system resilience. First, we propose a resilience score based on a piecewise linear approximation to a resilience curve. Using multicriteria decision analysis principles, we score system design alternatives in terms of system-specific capabilities. We estimate the relevance of these capabilities to resilience curve parameters associated with resilience ***, we interpret the derivatives of resilience with respect to the curve parameter values as the leverage of these parameters. Using multiple levels of weighted sums of the scores, we calculate the first order impact of system design choices first on a proxy for the generic resilience parameters and then on resilience, which allows situational characteristics to be incorporated in their natural terminology while mapping their impact on resilience with a traceable logic. We illustrate the approach by using existing materials to develop an example comparing engineered designs for minimizing post-wildfire flood impacts.

关键词： Decision analysis multicriteria decision analysis Resilience System design

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Aberrant Th2 inflammation drives dysfunction of alveolar macrophages and susceptibility to bacterial pneumonia

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Cellular & molecular Immunology 2018年第5期15卷 480-492页

作者： emily K moser Natania S Field Paula m Oliver Cell Pathology Division Children’s Hospital of PhiladelphiaPhiladelphiaPA 19104USA Cell and molecular Biology Program Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Pathology and Laboratory medicine University of PennsylvaniaPhiladelphiaPA 19104USA

The ubiquitin ligase,Itch,is required to prevent autoinflammatory disease in mice and ***-deficient mice develop lethal pulmonary inflammation characterized by the production of Th2 cytokines(for example,interleukin-4(IL-4));however,the contribution of Itch to immune defense against respiratory pathogens has not been *** found that Itch-deficient mice were highly susceptible to intranasal infection with the respiratory pathogen Klebsiella *** Itch-deficient mice exhibited increased immune cell infiltration,cytokine levels and bacterial burden in the respiratory tract compared with control ***,numbers of resident alveolar macrophages were reduced in the lungs from Itch-deficient mice both before and after *** levels of Th2 cytokines in the respiratory tract correlated with deceased alveolar macrophages,and genetic ablation of IL-4 restored alveolar macrophages and host defense to *** in Itch-deficient mice,suggesting that loss of alveolar macrophages occurred as a consequence of Th2 *** transfer of Itch−/−CD4+T cells into Rag−/−mice was sufficient to drive reduction in numbers of Itch-replete alveolar ***,we found that Stat6 signaling downstream of the IL-4 receptor directly reduced fitness of alveolar macrophages when these cells were exposed to the Itch−/−inflamed respiratory *** data suggest that Th2 inflammation directly impairs alveolar macrophage fitness in Itch−/−mice,and elucidate a previously unappreciated link between Th2 cells,alveolar macrophages and susceptibility to bacterial infection.

关键词： alveolar macrophage bacterial pneumonia Itch Th2 cell

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Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

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Neural Regeneration Research 2021年第11期16卷 2132-2140页

作者： Tara m.Caffrey emily B.Button Jerome Robert Djavad mowafaghian Center for Brain Health University of British ColumbiaVancouverBCCanada Department of Pathology University of British ColumbiaVancouverBCCanada Institute of Clinical Chemistry University Hospital of ZurichZurichSwitzerland

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and *** supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular *** many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the *** order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular *** towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous *** and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the *** advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential *** innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

关键词： Alzheimer’s disease cerebrovasculature in vitro model neurodegeneration neurovascular unit

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Lymphocyte phenotypes in wild-caught rats suggest potential mechanisms underlying increased immune sensitivity in post-industrial environments

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Cellular & molecular Immunology 2012年第2期9卷 163-174页

作者： Ashley m Trama Zoie E Holzknecht Anitra D Thomas Kuei-Ying Su Sean m.lee emily E Foltz Sarah E Perkins Shu S Lin William Parker Department of Surgery Duke University Medical Center Durham NC 27710 USA Cardiff School of Biosciences Cardiff CFIO 3AX UK Department of Immunology Duke University Medical Center Durham NC 27710 USA

The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease.

关键词： allergy autoimmunity biome hygiene immune regulation

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Better together?Comparing physical activity of parents walking outdoors with and without their child

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Sports medicine and Health Science 2023年第3期5卷 190-195页

作者： Patrick m.Filanowski emily Slade Department of Sport Science&management Xavier UniversityCincinnatiOH45207USA Department of Biostatistics University of KentuckyLexingtonKY40506USA

This study compares the physical activity levels and enjoyment of parents(n=50;age=41.8±4.0 years)during outdoor,self-paced walking sessions while walking alone and when walking with their 6-to-12-year-old *** counts,moderate-to-vigorous physical activity(mVPA),vigorous physical activity,and enjoyment were compared using paired *** modeling was used to examine the impact of children's age and adults'and children's body mass index on the disparity in step counts experienced by *** attained high percentages of time spent in mVPA while walking alone(99.8%)and when walking with their child(96.6%).However,more of this time was categorized as vigorous physical activity when walking alone(13.6%vs.3.0%,p=0.006).Adults'step counts decreased by an average of 6.4%while walking with their child compared to walking alone(pmal-weight adults(p=0.042).Although adults obtained higher step counts and vigorous physical activity while walking alone,they enjoyed walking more with their child(pmaking recommendations for parent-child co-participation in physical activity,and parents may wish to supplement their physical activity obtained while walking with their child(ren)with additional activities that result in vigorous physical activity.

关键词： alone walking younger

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Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World Journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： emily m Lin Jun Gong Samuel J Klempner Joseph Chao Department of Internal medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research Institute Los AngelesCA 90404United States Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. microsatellite instability(mSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with mSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

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Impacts and challenges of United States medical students during the COVID-19 pandemic

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World Journal of Clinical Cases 2020年第15期8卷 3136-3141页

作者： Stacey Rolak Alexis m Keefe emily L Davidson Prabesh Aryal Sandesh Parajuli Department of medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States College of medicine Nepalese Army Institute of Health SciencesKathmandu 44600Nepal Division of Nephrology Department of Internal MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States

The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)*** in their pre-clinical years have transitioned to online courses and *** in their clinical years are not permitted on clinical rotations,and face uncertainties in career exploration and the residency application *** students in all stages of training are volunteering and helping their *** future presence of COVID-19 throughout the United States is unknown,and medical students are eager to return to their *** paper outlines current challenges in medical student education and the various responses that have been *** also discuss possible future directions for students through involvement in telemedicine,outpatient clinic visits,and non-respiratory inpatient care tasks as adequate personal protective equipment,COVID-19 testing,and resources become more widely available.

关键词： COVID-19 Education medical students Telemedicine Healthcare delivery Schools

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