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Transcriptional regulation of secretory capacity by bZip transcription factors

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Frontiers in Biology 2015年第1期10卷 28-51页

作者： Rebecca m. FOX Deborah J. andrew The Department of Cell Biology The Johns Hopkins University School of Medicine Baltimore MD 21205 USA

Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum （ER）, the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response （UPR）. Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR-ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.

关键词： bZip transcription factors endoplasmic reticulum Golgi secretion secretory capacity secretory vesicles

Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice

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Neural Regeneration Research 2020年第1期15卷 136-144页

作者： andrew RClark Chia George Hsu m A Hassan Talukder mark Noble John CElfar Center for Orthopaedic Research and Translational Science Penn State Hershey College of MedicineMilton S.Hershey Medical CenterHersheyPAUSA Department of Orthopaedics The University of Rochester Medical CenterRochesterNYUSA Department of medicine Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterNYUSA Department of Biomedical Genetics The University of Rochester Medical CenterRochesterNYUSA

Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional *** hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve *** with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP *** a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle *** findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal *** animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on march 31,2017.

关键词： 4-aminopyridine electron microscopy functional recovery nerve conduction velocity peripheral nerve injury pharmacokinetics transdermal administration

A deep convolutional neural network for real-time full profile analysis of big powder diffraction data

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npj Computational materials 2021年第1期7卷 671-679页

作者： Hongyang Dong Keith T.Butler Dorota matras Stephen W.T.Price Yaroslav Odarchenko Rahul Khatry andrew Thompson Vesna middelkoop Simon D.m.Jacques andrew m.Beale Antonis Vamvakeros Department of Chemistry University College London20 Gordon StreetLondon WC1H 0AJUnited Kingdom ScimL Scientific Computer DivisionSTFCRutherford Appleton LaboratoryHarwell OX110QXUnited Kingdom Finden Limited Merchant House5 East St Helens StreetAbingdon OX145EGUnited Kingdom National Physical Laboratory Hampton RoadTeddington TW110LWUnited Kingdom Flemish Institute for Technological Research VITO NVBoeretang 200Mol 2400Belgium Research Complex at Harwell Rutherford Appleton LaboratoryHarwell Science and Innovation CampusDidcotOX110FA OxfordshireUnited Kingdom Present address:Diamond Light Source Harwell Science and Innovation CampusDidcotOxfordshire OX110DEUnited Kingdom Present address:The Faraday Institution Quad OneHarwell Science and Innovation CampusOX110RA OxfordshireUnited Kingdom

We present Parameter Quantification Network(PQ-Net),a regression deep convolutional neural network providing quantitative analysis of powder X-ray diffraction patterns from multi-phase *** network is tested against simulated and experimental datasets of increasing complexity with the last one being an X-ray diffraction computed tomography dataset of a multi-phase Ni-Pd/CeO_(2)-ZrO_(2)/Al_(2)O_(3) catalytic material system consisting of ca.20,000 diffraction *** is shown that the network predicts accurate scale factor,lattice parameter and crystallite size maps for all phases,which are comparable to those obtained through full profile analysis using the Rietveld method,also providing a reliable uncertainty measure on the *** main advantage of PQNet is its ability to yield these results orders of magnitude faster showing its potential as a tool for real-time diffraction data analysis during in situ/operando experiments.

关键词： network powder analysis

Genetic mapping and survey of powdery mildew resistance in the wild Central Asian ancestor of cultivated grapevines in Central Asia

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Horticulture Research 2020年第1期7卷 1444-1458页

作者： Summaira Riaz Cristina m.menéndez Alan Tenscher Daniel Pap m.andrew Walker Department of Viticulture and Enology University of CaliforniaDavisCA 95616USA Instituto de Ciencias de la Vid y del Vino(ICVV) Universidad de La Rioja-CSICGobierno de La RiojaCarretera de Burgos Km6Finca La GrajeraLogroñoLa Rioja 26007Spain

Cultivated grapevines(Vitis vinifera)lack resistance to powdery mildew(Pm)with few *** to this pathogen within *** has been reported in earlier studies and identified as the Ren1 locus in two Central Asian table grape *** Pm-resistant cultivated varieties and accessions of the wild ancestor *** *** were soon identified raising questions regarding the origin of the *** this study,F1 breeding populations were developed with a Pm susceptible *** *** breeding line and a Pm-resistant *** *** was carried out with five Ren1 locus linked SSR markers.A Pm resistance locus explaining up to 96%of the phenotypic variation was identified in the same genomic position,where the Ren1 locus was previously *** SSR marker alleles linked with the resistance locus were *** report results of Pm resistance in multiple accessions of *** collected as seed lots or cuttings from five countries in the Caucasus and Central Asia.A total of 20 females from 11 seed lots and 19 males from nine seed lots collected from Georgia,Armenia,and Azerbaijan were resistant to *** male and one female plant collected as cuttings from Afghanistan and Iran were also resistant to *** analysis of markers linked with the Ren1 locus in conjunction with disease evaluation data found a high diversity of allelic haplotypes,which are only possible via recombination events occurring over a long time *** analysis of two alleles of the SSR marker that cosegregates with the resistance found SNPs that were present in the wild progenitor and in cultivated *** levels of Pm resistance among the tested accessions were also *** lines of evidence suggest that the powdery mildew fungus may have been present in Asia for a longer time than currently thought,giving the wild progenitor *** *** time to coevolve with and develo

关键词： breeding resistance Central

multimodal alarm behavior in urban and rural gray squirrels studied by means of observation and a mechanical robot

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Current Zoology 2010年第3期56卷 313-326页

作者： Sarah R.PARTAN andrew G FULmER maya A.m.GOUNARD Jake E.REDmOND Hampshire College School of Cognitive Science

Urbanization of animal habitats has the potential to affect the natural communication systems of any species able to survive in the changed environment. Urban animals such as squirrels use multiple signal channels to communicate, but it is un- known how ttrbanization has affected these behaviors. multimodal commtmication, involving more than one sensory modality, can be studied by use of biomimetic mechanical animal models that are designed to simulate the multimodal signals and be pre- sented to animal subjects in the field. In this way the responses to the various signal components can be compared and contrasted to determine whether the multimodal signal is made up of redundant or nonredundant components. In this study, we presented wild gray squirrels in relatively urban and relatively rural habitats in Western massachusetts with a biomimetic squirrel model that produced tail flags and alarm barks in a variety of combinations. We found that the squirrels responded to each unimodal component on its own, the bark and tail flag, but they responded most to the complete multimodal signal, containing both the acoustic and the moving visual components, providing evidence that in this context the signal components are redundant and that their combination elicits multimodal enhancement. We expanded on the results of Partan et al. （2009） by providing data on sig- naling behavior in the presence and absence of conspecifics, suggesting that alarm signaling is more likely if conspecifics are present. We found that the squirrels were more active in the urban habitats and that they responded more to tail flagging in the urban habitats as compared to the rural ones, suggesting the interesting possibility of a multimodal shift from reliance on audio to visual signals in noisier more crowded urban habitats [Current Zoology 56 （3）： 313-326, 2010].

关键词： Alarm behavior Communication Gray squirrel Sciurus carolinensis multisensory signaling Redundancy Urbanization Ethorobotics

Statins,platelets,and the elderly

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Journal of Geriatric Cardiology 2007年第4期4卷 218-219页

作者： andrew m.Kates Heart Disease Prevention Program 660 South Euclid Ave Campus Box 8086 Washington University School of Medicine St. Louis MO USA

　　As a class of drugs, statins have gained renown for their ability to effectively reduce cardiovascular events in both patients with heart diseases (secondary prevention)and in those who, while not with manifest heart disease (primary prevention), are at increased risk based on a variety of risk factors including hypertension, diabetes, and age.……

关键词： LDL Statins,platelets,and the elderly

Chemoprevention of esophageal adenocarcinoma

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Gastroenterology Report 2020年第4期8卷 253-260,I0001页

作者： Erik J.Snider andrew m.Kaz John m.Inadomi William m.Grady Division of Gastroenterology Department of Internal MedicineUniversity of Washington School of MedicineSeattleWAUSA Gastroenterology Section VA Puget Sound Health Care SystemSeattleWAUSA Clinical Research Division Fred Hutchinson Cancer Research CenterSeattleWAUSA

Esophageal adenocarcinoma(EAC)is a major cause of cancer-related death,particularly in Western populations,and is rapidly rising in Asian populations at this *** all EACs develop from the precursor lesion Barrett’s esophagus(BE),which is the most significant risk factor for ***,the rates of progression from BE to EAC are low and patients with BE are ***,any strategy for EAC prevention must carry a low risk of harm in order to be clinically *** current EAC-screening and BE-surveillance methods carry some procedural risk and are burdensome,there is an opportunity for chemoprevention,*** or dietary factors that may prevent BE from progressing to EAC.A variety of candidate chemoprevention therapies have been assessed to ***-pump inhibitors(PPIs)are the best studied and have modest EAC-chemoprevention efficacy in BE patients,with a recent randomized trial showing that high-dose PPI may be more effective than low-dose *** and other non-steroidal anti-inflammatory drugs have moderate quality observational and randomized-trial evidence for preventing progression of BE to EAC,but their risks for harm have precluded their routine clinical *** therapies(statins,metformin,female sex hormones)generally do not have strong evidence to support their use in EAC *** progress has been made in this field,there is still a need for more effective and safe chemoprevention therapies for EAC.

关键词： Barrett’s esophagus esophageal adenocarcinoma chemoprevention

Insect sampling in forest ecosystems

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Insect Science 2005年第5期12卷 399-400页

作者： andrew m. Liebhold USDA Forest Service Northeastern Research Station180 Canfield St. Morgantown WV 26505 USA

Forests have long been recognized as excellent model systems for studying insect ecology. The fact that many forests＇ ecosystems still function in a semi-natural state, with little influence from human disturbance, provides unique opportunities for understanding co-evolved community and population processes. Unfortunately the structural complexity of forests and the sheer size of trees often pose formidable problems when attempting to sample insects in forests. As such, any scientist embarking on a study of forest insect ecology would be well-advised to carefullv plan their sampling efforts.

关键词：昆虫森林系统生态环境取样方法

Cholecystocolocutaneous fistula: a case report

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Hepatobiliary & Pancreatic Diseases International 2006年第3期5卷 462-464页

作者： Badrl m.Shrestha andrew Wyman Northern General Hospital Herries Road SheffieldS5 7AUUK

BACKGROUND: Cholecystocolocutaneous fistula (CCCF) is a rare complication of gallstone disease resulting from spillage of gallstones from perforation of an empyema of the gallbladder, which can pose diagnostic dilemmas. We describe a patient, who presented initially with a swelling followed by discharging sinuses on her right flank where a diagnosis of CCCF was made and was treated surgically with satisfactory outcome. mETHODS: A computed tomography (CT) scan showed an ill-defined soft tissue mass in the right subhepatic space and a fistulogram demonstrated passage of contrast into the gallbladder fossa and hepatic flexure of colon. At laparotomy,a cutaneous fistula containing two pigment stones led to the gallbladder fossa and hepatic flexure of colon. RESULTS: Debridement of infected granulation tissues which had replaced the gallbladder, closure of the cystic duct stump and colonic fistula followed by excision of the fistula tract led to complete resolution. CONCLUSIONS: CCCF is a rare complication of perforated gallbladder with spillage of calculi, and a fistulogram is helpful in establishing the diagnosis. This case highlights the importance of retrieving spilled stones following interventions in the gallbladder to prevent the complication.

关键词： cholecystocolocutaneous fistula gallstones fistulogram