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Endosomal trafficking defects in patient cells with KIAA1109 biallelic variants

Genes & Diseases 2019年第1期6卷 56-67页

作者： Megan S.Kane Callie J.Diamonstein Natalie Hauser john f.Deeken john E.Niederhuber Thierry Vilboux Inova Translational Medicine Institute Inova Health SystemFairfaxVAUnited States Department of Medicine Virginia Commonwealth UniversityRichmondVAUnited States Department of Public Health Sciences University of Virginia School of MedicineCharlottesvilleVAUnited States Department of Oncology and Surgery Johns Hopkins University School of MedicineBaltimoreMDUnited States

The uncharacterized gene KIAA1109 has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis,craniofacial and/or cardiac *** have identified two additional patients with compound heterozygous KIAA1109 variants presenting with the same neurological *** mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our *** hypothesized that KIAA1109 function could be conserved relative to the fly gene tweek and examined endocytosis and endosome recycling in patient ***,we examined the structure of the cytoskeleton and cilia based on functional overlap with endocytosis and several known etiologies for neuronal migration *** primary dermal fibroblasts from one patient and a healthy donor,we performed immunofluorescence and endocytosis assays to examine the endosomal,cytoskeletal,and ciliary cellular *** found notable abnormalities in endosomal trafficking and endosome recycling *** also observed changes in the actin cytoskeleton and cilia structural *** conclude that the function of KIAA1109 in humans may indeed overlap with the function of the Drosophila ortholog,resulting in perturbations to endosomal trafficking and the actin *** alterations have ripple effects,altering many pathways that are critical for proper neuronal migration and embryonic development.

关键词： Cilia Endocytosis KIAA1109 Neurological malformation Vesicular trafficking

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Helicobacter pylori infection and extragastric disorders in children: A critical update

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World Journal of Gastroenterology 2014年第6期20卷 1379-1401页

作者： Lucia Pacifico john f Osborn Valeria Tromba Sara Romaggioli Stefano Bascetta Claudio Chiesa Department of Pediatrics Sapienza University of Rome Department of Health Sciences and Infectious Diseases Sapienza University of Rome Institute of Translational Pharmacology National Research Council

Helicobacter pylori(H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in thelast decades, abetted by modern clinical practices, may have other health consequences.

关键词： Helicobacter pylori Children Iron deficiency anemia Chronic idiopathic thrombocytopenic purpura Growth retardation Asthma Allergy Diabetes mellitus

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“Digging in the Dirt”faecal microRNAs as dietary biomarkers of host-microbe interactions

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Hepatobiliary Surgery and Nutrition 2022年第2期11卷 292-294页

作者： Gerard M.Moloney john f.Cryan Gerard Clarke Department of Anatomy&Neuroscience University College CorkCorkIreland APC Microbiome Ireland University College CorkCorkIreland Department of Psychiatry and Neurobehavioural Science University College CorkCorkIreland

The role of diet and nutrition in maintaining a healthy lifestyle has become a central part of chronic disease prevention(1).Chronic conditions such as cancer,Inflammatory bowel disease(IBD)and obesity are more prevalent in people with poor diets(2).food consumption is controlled by physiological systems such as the gut-microbiome and distinct neuroendocrine pathways that overlap to promote host nutritional gain resulting in people living longer healthier lives(3).A recent analysis of the global burden of disease by the World Health Organization(WHO),noted that factors associated with poor diet,including obesity and malnutrition,critically undermine health and *** note that undernutrition,deficiencies in key nutrients and obesity have high social and economic *** disease,cancer,diabetes,and respiratory diseases account for 77%of all diseases and are responsible for 86%of all premature deaths(4).There is an appreciation that diets that reduce or eliminate red meats and animal fats results in the reduction of many of the indicators of poor diet,such as body mass index(BMI)and levels of cholesterol in the blood.

关键词： prevention eliminate overlap

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Active surveillance monitoring： the role of nove biomarkers and imaging

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Asian Journal of Andrology 2015年第6期17卷 882-884,I0006页

作者： john f Ward Scott E Eggener Department of Urology The University of TexasMD Anderson Cancer Center Houston TX USA Department of Urology University of ChicagoChicago IL USA.

＂CANCER＂ is a disease state that leads to progressive illness that is uniformly fatal without treatment. Hippocrates invoked the Greek word karkinos, or ＂crab＂ to describe tumors he observed. for centuries, ＂CANCER＂ remained a disease that was recognized primarily in its locally advanced or metastatic stage, when it was almost uniformly fatal.

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Business, government, and society : a managerial perspective : text and cases / George A. Steiner, john f. Steiner. 9th ed.

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2000年

作者： George A. Steiner john f. Steiner.

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Characterizing drought in California:new drought indices and scenario-testing in support of resource management

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Ecological Processes 2018年第1期7卷 1-13页

作者： Lorraine E.flint Alan L.flint john Mendoza Julie Kalansky f.M.Ralph U.S.Geological Survey 6000 J.StSacramentoCA 95819USA Sonoma County Water Agency 404 Aviation Dr.Santa RosaCA 95403USA Scripps Institution of Oceanography 9500 Gilman Dr.La JollaCA 92093USA

Introduction:California’s recent drought(2012–2016)has implications throughout the state for natural resource management and adaptation planning and has generated many discussions about drought characterization and *** study characterizes drought conditions with two indices describing deficits in natural water supply and increases in landscape stress developed on the basis of water balance modeling,at a fine spatial scale to assess the variation in conditions across the entire state,and provides an in-depth evaluation for the Russian River basin in northern California to address local resource management by developing extreme drought scenarios for consideration in planning and ***:We employed the USGS Basin Characterization Model to characterize drought on the basis of water supply(a measure of recharge plus runoff)and landscape stress(climatic water deficit).These were applied to the state and to the Russian River basin where antecedent soil moisture conditions were evaluated and extreme drought scenarios were developed and run through a water management and reservoir operations model to further explore impacts on water ***:Drought indices indicated that as of the end of water year 2016 when reservoirs were full,additional water supply and landscape replenishment of up to three average years of precipitation in some locations was needed to return to normal *** soil conditions in the Russian River were determined to contribute to very different water supply results for different years and were necessary to understand to anticipate proper watershed response to *** drought scenarios manifested very different kinds of drought and recovery and characterization helps to guide the management response to ***:These scenarios and indices illustrate how droughts differ with regard to water supply and landscape stress and how long warm droughts recover much more slowly than short very dry dro

关键词： California drought Russian River Water supply Basin Characterization Model

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Human development across the lifespan john S. Dacey, john f. Travers. 5th ed.

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2002年

作者： john S. Dacey john f. Travers.

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Role of Mg on Structure and Mechanical Properties in Alloy 718

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工程科学学报 1989年第6期11卷 560-567页

作者：徐志超 ,谢锡善 ,屈波 ,陈国良 ,Radavich john f 北京科技大学北京 School of Materials Engineering Purdue University

The role of Mg in alloy/718 has been systematically investigated. Mg raises not only high temperature tensile and stress-rupture ductilities but also increases considerably smooth and notch stress-rupture life. Mg containing alloy 718M is free of stress-rupture notch sensitivity. Mg improves creep and fatigue interaction properties (LCf or cyclic stress rupture) at any grain size. The basic role of Mg is equilibrium segregation at grain boundaries which helps to change continuous grain beundary (5-Ni3Nb morphology to discrete globular form which has a retardation effect on intergranular fracture. Mg promotes the change from intergranular to transgranular fracture mode.

关键词： superalloy creep and fatigue mechanical properties

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Contemporary diagnostics and treatment options for female stress urinary incontinence

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Asian Journal of Urology 2018年第3期5卷 141-148页

作者： Allert M.de Vries john P.f.A.Heesakkers Department of Urology Radboud University Medical CenterNijmegenThe Netherlands

Stress urinary incontinence is not a deadly disease,but for the large population of women suffering from it,it is a very important *** in the continuously aging population all over the world,there is more and more need for treatment of this serious medical *** of female stress urinary incontinence exists already for *** the 20th century invasive treatments like Burch colposuspension and pubovaginal slings were the mainstay of surgical *** introduction of the midurethral sling made the procedure less invasive and accessible for more *** there are many options available and the field is developing *** recent years many new medical devices have been developed,that increase the number of treatment options available and make it possible to find a suitable solution for the individual patient based on subjective and objective results and the chances of *** manuscript provides an introduction to the therapeutical options that are available nowadays for female stress urinary incontinence.

关键词： female Stress urinary incontinence Treatment Urinary incontinence Pelvic floor muscle training Suburethral slings

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Kinase inhibitors:look beyond the label on the bottle

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Cancer Drug Resistance 2019年第4期2卷 1032-1043页

作者： Paul Dent Andrew Poklepovic Laurence Booth john f.Hancock Department of Biochemistry and Molecular Biology1 Virginia Commonwealth UniversityRichmondVA 23298-0035USA Department of Medicine Virginia Commonwealth UniversityRichmondVA 23298-0035USA Department of Integrative Biology and Pharmacology University of Texas Health Science CenterHoustonTX 77030USA

The majority of scientists working in the field of cancer experimental therapeutics recognize that many drugs that claim to be“specific”for one target enzyme in fact regulate to varying degrees the activities of other additional protein *** of these targets are known and are recognized as being an essential component of a drug’s ***,many other targets fall into the category of“unknown unknowns”.Thus,the collective therapeutic outcome for almost all clinically relevant drugs is reliant on both the claimed primary and secondary“on”targets as well as some of the unexpected unknown“off”*** review discusses the biology of several fDA approved cancer therapeutic drugs whose initial reported targets only represented the tip-of-the-iceberg in terms of how each agent acted as an anti-tumor *** review also discusses a putative thorough pre-visualization methodology for drug-based research,prior to executing any wet *** approaches should be performed in an agnostic fashion and be based in part on the clinically safe drug’s C max and its area under the curve in a *** on tumor heterogeneity,considerations of how to approach developmental therapeutics in the age of“personalized medicine”are also discussed.

关键词： Autophagy histone deacetylase chaperone cancer

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