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Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants

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Journal of Integrative plant Biology 2014年第3期56卷 192-220页

作者： Zhaoliang Zhang Hong Liao william J.Lucas Department of plant Biology College of Biological Sciences University of California State Key Laboratory for Conservation and Utilization of Subtropical Agro‐Bioresources Root Biology Center South China Agricultural University

As an essential plant macronutrient, the low availability of phosphorus （p） in most soils imposes serious limitation on crop production. plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate （pi） to maintain p homeostasis. Spatio-temporal molecular, physiological, and biochemical pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehen- sive understanding of the molecular events underlying control over p homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for p use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global p supplies.

关键词： Adaptation crop engineering strategies hormone networks local and long-distance sensing phosphate p use efficiency stress responses systemic signaling transcriptional regulation transport systems

An Arabidopsis Lipid Flippase Is Required for Timely Recruitment of Defenses to the Host- pathogen Interface at the plant Cell Surface

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Molecular plant 2017年第6期10卷 805-820页

作者： william Underwood Andrew Ryan Shauna C. Somerville Energy Biosciences Institute Department of plant and Microbial Biology University of California Berkeley CA 94720 USA USDA-ARS Red River Valley Agricultural Research Center Sunflower and Plant Biology Research Unit Fargo ND 58102-2765 USA Division of Biological Sciences University of California San Diego CA 92161 USA

Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. TheArabidopsis pENETRATION 3 （pEN3） ATp binding cassette （ABC） transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates within papillae. However, the trafficking pathways and regulatory mechanisms contributing to recruitment of pEN3 and other defenses to the host-pathogen interface are poorly understood. Here, we report a confocal microscopy-based screen to identify mutants with altered localization of pEN3-GFp after inoculation with powdery mildew fungi. We identified a mutant, aberrant localization of pEN3 3 （alp3）, displaying accumulation of the normally plasma membrane （pM）-Iocalized pEN3-GFp in endomembrane compartments. The mutant was found to be disrupted in the p4-ATpase AMINOpHOSpHOLIpID ATpASE 3 （ALA3）, a lipid flippase that plays a critical role in vesicle formation. We provide evidence that pEN3 undergoes continuous endocytic cycling from the pM to the trans-Golgi network （TGN）. In alp3, pEN3 accumulates in the TGN, causing delays in recruitment to the host-pathogen interface. Our results indicate that pEN3 and other defense proteins continuously cycle through the TGN and that timely exit of these proteins from the TGN is critical for effective pre-invasive immune responses against powdery mildews.

关键词： plant-microbe interactions defense responses protein traffic and secretion macromolecular trafficking papilla ABC transporter

Tumor biopsy and patient enrollment in clinical trials for advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第13期23卷 2448-2452页

作者： Lorenza Rimassa Maria Reig Giovanni Abbadessa Markus peck-Radosavljevic william harris Vittorina Zagonel Davide pastorelli Elena Rota Caremoli Camillo porta Nevena Damjanov Hitendra patel Bruno Daniele Maria Lamar Brian Schwartz Terri Goldberg Armando Santoro Jordi Bruix Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research Center Barcelona Clinic Liver Cancer Group Liver UnitHospital ClinicUniversity of BarcelonaIDIBAPSCIBERehd Clinical Development Ar QuleInc Department of Gastroenterology HepatologyEndrocrinologyand NephrologyKlinikum Klagenfurt am Worthersee Department of Medicine Oncology DivisionUniversity of Washington School of Medicine Department of Clinical and Experimental Oncology Medical Oncology 1Veneto Institute of Oncology-IRCCS Department of Oncology Santa Maria del Prato Hospital Department of Oncology Papa Giovanni XXIII Hospital Department of Oncology Fondazione IRCCS Policlinico San Matteo Division of Gastrointestinal Oncology Abramson Cancer Center of the University of Pennsylvania Department of Medicine The University of Arizona Cancer Center Department of Oncology G.Rummo Hospital Clinical Development Daiichi Sankyo Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research CenterHumanitas University

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.

关键词： Liver neoplasms Biopsy Biomarkers Clinical trial Tumor

High prevalence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area,Tanzania,after 20 years of community directed treatment with ivermectin

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Infectious Diseases of poverty 2018年第1期7卷 622-634页

作者： Bruno p.Mmbando patrick Suykerbuyk Mohamed Mnacho Advocatus Kakorozya william Matuja Adam Hendy Helena Greter williams H.Makunde Robert Colebunders National Institute for Medical Research Tanga Research CentreTangaTanzania Global Health Institute University of AntwerpAntwerpBelgium Muhimbili National Hospital Dar es SalaamTanzania Enhance Tanzania Foundation Dar es SalaamTanzania Muhimbili University of Health and allied Sciences Dar es SalaamTanzania University of Texas Medical Branch GalvestonTXUSA

Background:Epilepsy is a neurological disorder with a multitude of underlying causes,which may include infection with Onchocerca volvulus,the parasitic worm that causes human onchocerciasis.A survey carried out in 1989 revealed a high prevalence of epilepsy(1.02%overall,ranging from 0.51 to 3.71%in ten villages)in the Mahenge area of Ulanga district,an onchocerciasis endemic region in south eastern *** study aimed to determine the prevalence and incidence of epilepsy following 20 years of onchocerciasis control through annual community directed treatment with ivermectin(CDTI).Methods:The study was conducted in January 2017 in two suburban and two rural villages in the Mahenge ***-todoor household visits were carried out by trained community health workers and data assistants to screen for persons suspected of having epilepsy,using a standardised *** with suspected epilepsy were then interviewed and examined by a neurologist for case *** associated epilepsy was defined as epilepsy without an obvious cause,with an onset of seizures between the ages of 3-18 years in previously healthy *** each village,fifty males aged≥20 years were tested for onchocerciasis antibodies using an OV16 rapid test and were examined for presence of onchocerciasis *** aged 6-10 years were also tested using OV16 ***:5117 individuals(median age 18.5 years,53.2%female)from 1168 households were screened.244(4.8%)were suspected of having epilepsy and invited for neurological *** of epilepsy was 2.5%,with the rural villages having the highest rate(3.5%vs 1.5%),ppilepsy was 111 cases(95%CI:73-161)per 100000 person-years,while that of onchocerciasis associated epilepsy was 131(95%CI:70-223).prevalence of OV16 antibodies in adult males and among children 6-10 years old was higher in rural villages than in suburban villages(76.5%vs 50.6,and 42.6%vs 4.7%respectively),(p

关键词： Epilepsy Onchocerciasis Mahenge Tanzania

Cancer vaccines:shared tumor antigens return to the spotlight

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Signal Transduction and Targeted Therapy 2020年第1期5卷 324-325页

作者： Lijin Li S.peter Goedegebuure william Gillanders Department of Surgery Washington University School of MedicineSt LouisMOUSA The Alvin J.Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine St LouisMOUSA

Sahin et *** reported interim data from a phase 1 clinical trial(NCT02410733)treating melanoma patients with a RNAlipoplex vaccine(RNA-LpX),targeting melanoma TAA.1 The trial is a multicenter,non-randomized,open-label,dose-escalation trial designed to evaluate the safety and tolerability of BNT111 targeting four melanoma TAA(NY-ESO-1,MAGE-A3,tyrosinase,and TpTE).Secondary endpoints include vaccine-induced immune responses and clinical response of patients with measurable disease.

关键词： vaccine melanoma clinical

Characteristics of magnetic dipolarizations in the vicinity of the substorm onset region observed by THEMIS

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Earth and planetary physics 2021年第3期5卷 239-250页

作者： Suping Duan Chi Wang Weining william Liu ZhaoHai He State Key Lab of Space Weather National Space Science CenterChinese Sciences AcademyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

With conjunction observations of electromagnetic fields and plasma from Time History of Events and Macroscale Interactions during Substorm(THEMIS)in the near-Earth magnetotail,we investigate the spatial and temporal properties of substorm dipolarizations in the near-Earth plasma sheet(NEpS)during a substorm at 03:23 UT on 12 February *** dipolarizations with different features are detected by three near-Earth THEMIS probes(THA(p5),THD(p3)and THE(p4))in the *** the current sheet with a large plasma beta value(β>2,whereβis the ratio of the plasma thermal pressure to the magnetic pressure),the dipolarization within the substorm onset region,(−10.4,2.8,−2.6)RE_gsm,has a large initial magnetic field elevation angle,θ>60°,θ=arctan(Bz/(Bx2+By2)1/2),and is accompanied by energetic ion(tens to hundred keV)dispersionless injection detected by THD(p3).This substorm onset dipolarization is characterized by Bx and By components around 0 nT with significant *** Bz component increases sharply and its subsequent magnitude approaches the total magnetic field,*** maximum value of the elevation angle approaches 85°during the later substorm expansion *** the NEpS withβ~1,the dipolarization outside the substorm onset region is characterized by a magnetic elevation angle with a small beginning value ofθp enhancements during the substorm expansion *** maximum value of the elevation angle approaches to 70°during the later substorm expansion *** observation results indicate that characteristics of dipolarization with a large beginning elevation angle within the substorm onset region provide a new indicator to identify substorm onset location.

关键词： substorm magnetic dipolarization near-Earth plasma sheet magnetotail

Operative complications and economic outcomes of cholecystectomy for acute cholecystitis

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World Journal of Gastroenterology 2019年第48期25卷 6916-6927页

作者： Christopher p Rice Krishnamurthy B Vaishnavi Celia Chao Daniel Jupiter August B Schaeffer Whitney R Jenson Lance W Griffin william J Mileski School of Medicine University of Texas Medical BranchGalvestonTX 77555United States Department of Surgery University of Texas Medical BranchGalvestonTX 77555United States Department of Biostatistics University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Recent management of acute cholecystitis favors same admission(SA)or emergent cholecystectomy based on overall shorter hospital stay and therefore cost *** adopted the practice of SA cholecystectomy for the treatment of acute cholecystitis at our tertiary care center and wanted to evaluate the economic benefit of this *** hypothesized that the existence of complications,particularly among patients with a higher degree of disease severity,during SA cholecystectomy could negate the cost *** To compare complication rates and hospital costs between SA vs delayed cholecystectomy among patients admitted emergently for acute *** Under an IRB-approved protocol,complications and charges for were obtained for SA,later after conservative management(Delayed),or elective cholecystectomies over an 8.5-year *** were identified using the acute care surgery registry and billing *** was retrieved via EMR,operative logs,and Revenue Cycle *** severity of acute cholecystitis was graded according to the Tokyo ***18 categorizes acute cholecystitis by Grades 1,2,and 3 representing mild,moderate,and severe,*** were analyzed withχ2,Fisher’s exact test,ANOVA,ttests,and logistic regression;significance was set at ppatients(12.3%)received Delayed *** rates were increased after SA compared to Delayed cholecystectomy(18.5%vs 4.4%,p=0.004).The complication rates of patients undergoing delayed cholecystectomy was similar to the rate for elective cholecystectomy(7.4%,p=0.35).Mortality rates were 0.6%vs 0%for SA vs *** with moderate disease(Tokyo 2)suffered more complications among SA while none who were delayed experienced a complication(16.1%vs 0.0%,ppital charges for SA cholecystectomy were increased compared to a Delayed approach($44500±$59000 vs$35300±$16700,p=

关键词： Acute cholecystitis Tokyo guidelines Cholecystectomy Complications Delayed cholecystectomy

Development of the nervous system

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Transformative presidents： A Review of Definitions, Focused on the Reagan presidency

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作者： Dan H. Sanes Thomas A. Reh william A. harris

来源：畅想之星图书光盘版（南... 评论

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International Relations and Diplomacy 2015年第7期3卷 487-495页

作者： william A. p. Thompson Jr. University of Texas at Dallas Dallas USA

The most significant variable in ranking a president as transformative is the nature of his legacy. Reagan＇s legacy resulted from the Tea party＇s adoption of Reagan＇s conservative policy proposals, labeled the Reagan Revolution, or as Reagan defined in his farewell address, the ＂... Great Rediscovery, a recovery of our values and common sense＂（Skowronek, 1967, p. 95）. Transformative presidents create changes in the American political System. Stephen Skowronek has defined five transformational presidents whose administration transformed the American political system： Jefferson, Jackson, Lincoln, Franklin D. Roosevelt, and Reagan （Skowronek, 1967, p. 95）. Further, a comparison of the Reagan and Obama presidencies is included to explain why a president may be defined as being or not transformative. Each of these transformation repudiated their predecessor＇s policies. The Reagan Revolution enabled Reagan to become transformative by repudiating Carter＇s New Deal liberal and progressive policies. presidential scholars who deny the ability of presidents to become transformative do so based on their research that presidents lack the power to persuade Congress or change public opinion. Skowronek utilized Neustadt＇s theory of ＂periodization＂ to explain how the five transformational presidents each left through their ＂legacy＂, presidents who followed their policies. Reagan＇s followers included： George Bush, Clinton＇s centrist policies adhered to Reagan＇s, and George W. Bush. Obama was elected by repudiating his predecessor＇s policies. Whether Obama was transformative has yet to be determined.

关键词： transformative Reagan presidency periodization