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Complex peptide natural products: Biosynthetic principles, challenges and opportunities for pathway engineering

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Synthetic and Systems Biotechnology 2022年第1期7卷 631-647页

作者： Sebastian L.Wenski Sirinthra Thiengmag eric j.N.Helfrich Institute for Molecular Bio Science Goethe University Frankfurt60438Frankfurt am MainGermany LOEWE Center for Translational Biodiversity Genomics(TBG) 60325Frankfurt am MainGermany

Complex peptide natural products exhibit diverse biological functions and a wide range of physico-chemical *** a result,many peptides have entered the clinics for various *** main routes for the biosynthesis of complex peptides have evolved in nature:ribosomally synthesized and post-translationally modified peptide(RiPP)biosynthetic pathways and non-ribosomal peptide synthetases(NRPSs).Insights into both bioorthogonal peptide biosynthetic strategies led to the establishment of universal principles for each of the two *** universal rules can be leveraged for the targeted identification of novel peptide biosynthetic blueprints in genome sequences and used for the rational engineering of biosynthetic pathways to produce non-natural *** this review,we contrast the key principles of both biosynthetic routes and compare the different biochemical strategies to install the most frequently encountered peptide *** addition,the influence of the fundamentally different biosynthetic principles on past,current and future engineering ap-proaches is *** the different biosynthetic principles of both peptide biosynthetic routes,the arsenal of characterized peptide modifications encountered in RiPP and NRPS systems is largely *** continuous expansion of the biocatalytic toolbox of peptide modifying enzymes for both routes paves the way towards the production of complex tailor-made peptides and opens up the possibility to produce NRPS-derived peptides using the ribosomal route and vice versa.

关键词： Peptide natural products Non-ribosomal peptide synthetases Ribosomally synthesized and post-translationally modified peptides Biosynthesis Modification Engineering

Wheat yield prediction by zero sink and equilibrium-type soil phosphorus tests

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Pedosphere 2022年第4期32卷 543-554页

作者： Walter W.WENZEL Cornelia MESMER eric j.FLORIDA Markus PUSCHENREITER Holger KIRCHMANN Institute of Soil Research Department of Forest and Soil SciencesUniversity of Natural Resources and Life Sciences ViennaKonrad-Lorenz-Straße 24Tulln A-3430Austria College of Agriculture and Forestry Mindanao State University at NaawanNaawan 9023Philippines Department of Soil and Environment Swedish University of Agricultural SciencesBox 701475007 UppsalaLennart Hjelms väg 9Uppsala 75651Sweden

Diffusive gradients in thin films(DGT)measurements have been shown to outperform other phosphorus(P)tests in soils with strong P sorption,but this has not been confirmed for moderately weathered European *** compared the performance of DGT in predicting wheat grain yield in Swedish long-term fertility experiments with those of standard intensity(water-extractable P(P-H2O))and quantity(ammonium lactate-extractable P(P-AL))tests.A Mitscherlich-type model was used to fit wheat yield response to P application rates(0,15,30 or 35,and 45 kg P ha-1 year-1)in each individual trial replicate to estimate the maximum *** trials with clear plateau-type yield responses and the goodness of fit(R2)>0.75,relative yields(RYs)were calculated for each P treatment and plotted against the soil P test results(n=143).The goodness of the Mitscherlich-type fits decreased in the following order:DGT-measured P(P-DGT)(R2=0.35)>P-H2O(R2=0.18)>P-AL(R2=0.13).When excluding soils with P-AL:P-DGT≥0.1 L g-1,R2 was considerably improved to 0.55 for P-AL,0.46 for P-H2O,and 0.65 for P-DGT(n=61).At 95%of maximum yield,the upper limit of P deficiency for P-DGT was 44.8(the soils with P-AL:P-DGT<0.1 L g-1)and 61.9μg L-1(all soils),falling within the range reported for other European and Australian soils(6.0–142μg L-1).We show that in the investigated Swedish soils,DGT performed better than the quantity and intensity tests,which is attributed to its ability to capture P diffusion and resupply from the soil solid phase,similar to plant roots in the rhizosphere.

关键词： ammonium lactate-extractable phosphorus diffusive gradients in thin films(DGT) distribution coefficient long-term field experiment Mitscherlich-type model

Vestibular migraine in low-and lower-middle-income countries:A scoping review

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journal of Otology 2023年第3期18卷 173-184页

作者： eric K.Kim Amina Seguya May Htoo Thaw Peggy Tahir eric j.Formeister Christopher j.Waterworth Ali F.jaffer The Global Otolaryngology-Head and Neck Surgery Initiative USA Department of Otolaryngology-Head and Neck Surgery University of CaliforniaSan FranciscoSan FranciscoCAUSA Ear Nose and Throat SurgeonMulago National Referral HospitalKampalaUganda Eye ORL-HNS HospitalMandalayMyanmar UCSF Library University of CaliforniaSan FranciscoCAUSA Department of Otolaryngology-Head and Neck Surgery Duke UniversityDurhamNCUSA Department of Audiology and Speech Pathology The University of MelbourneVictoriaAustralia Nossal Institute for Global Health University of MelbourneVictoriaAustralia HearWell Audiology Clinic Dar es SalaamTanzania

Background:Vestibular migraine(VM)is a common cause of dizziness that is underrecognized,underdiagnosed,and challenging to effectively *** prevalence,appropriate diagnostic workup,and therapies for VM in low-and lower-middle-income countries(LLMICs)remain *** objective of this scoping review is to evaluate the current state of VM research in ***:PubMed,Embase,and Web of Science databases were searched to execute a scoping review of ***“vestibular diseases”and“vertigo”were used in combination with terms referring to LLMICs as defined by the World *** and abstract screening,full-text review,and data collection were conducted by two authors ***:Twenty-six studies were included in the scoping *** studies were cross-sectional(57.7%)or case studies/series(23.1%)and were conducted in urban settings only(92.3%).Geographic distribution of studies was skewed,with 65.4%of articles originating from *** prevalence of VM among clinic patients ranged from 0.3%to 33.3%.VM most frequently presented as headache,nausea and vomiting,and *** imaging,audiometry,and electronystagmography/videonystagmography were the three most commonly utilized diagnostic modalities in the dizziness *** most studied pharmacotherapies included calcium channel blockers,followed by beta-blockers and *** studies and series discussed less common VM pharmacotherapies,such as ayurvedic ***:There is a need for more VM research in LLMICs,including innovative diagnostic approaches and therapies that can improve VM care *** partnerships between LLMIC and highincome country researchers must expand vestibular research capacity and productivity in LLMICs.

关键词： Vestibular migraine Migraine Global Otolaryngology Scoping review

A balancing act: Optimizing free chlorine contact time to minimize iodo-DBPs, NDMA, and regulated DBPs in chloraminated drinking water

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journal of Environmental Sciences 2022年第7期34卷 315-325页

作者： Matthew A.Bloodgood Sridevi Anduri Chowdary eric j.Daiber Honglan Shi Caroline O.Granger Susan D.Richardson Student Services Authority U.S.Environmental Protection AgencyNational Exposure Research LaboratoryAthensGA 30605USA Department of Chemistry Missouri University of Science and TechnologyRollaMO 65409USA Department of Chemistry and Biochemistry University of South CarolinaColumbiaSC 29208USA

Many drinking water treatment plants in the U.S. have switched from chlorination to chloramination to lower levels of regulated trihalomethane(THM) and haloacetic acid(HAA) disinfection byproducts(DBPs) in drinking water and meet the current regulations. However, chloramination can also produce other highly toxic/carcinogenic, unregulated DBPs: iodoacids, iodo-THMs, and N-nitrosodimethylamine(NDMA). In practice, chloramines are generated by the addition of chlorine with ammonia, and plants use varying amounts of free chlorine contact time prior to ammonia addition to effectively kill pathogens and meet DBP regulations. However, iodo-DBPs and nitrosamines are generally not considered in this balancing of free chlorine contact time. The goal of our work was to determine whether an optimal free chlorine contact time could be established in which iodo-DBPs and NDMA could be minimized, while keeping regulated THMs and HAAs below their regulatory limits. The effect of free chlorine contact time was evaluated for the formation of six iodo-trihalomethanes(iodo-THMs), six iodo-acids, and NDMA during the chloramination of drinking water. Ten different free chlorine contact times were examined for two source waters with different dissolved organic carbon(DOC) and bromide/iodide. For the low DOC water at pH 7 and 8, an optimized free chlorine contact time of up to 1 h could control regulated THMs and HAAs, as well as iodo-DBPs and NDMA. For the high DOC water, a free chlorine contact time of 5 min could control iodo-DBPs and NDMA at both p Hs, but the regulated DBPs could exceed the regulations at pH 7.

关键词： Iodo-DBPs NDMA Disinfection byproducts Chloramine Drinking water Free chlorine contact time

糖尿病相关的足病的定义和标准(2023年更新版)

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感染、炎症、修复 2024年第1期25卷 80-85页

作者： jaap j.van Netten Sicco A.Bus jan Apelqvist Pam Chen Vivienne Chuter Robert Fitridge Frances Game Robert j.Hinchliffe Peter A.Lazzarini joseph Mills Matilde Monteiro-Soares Edgar j.G.Peters Katherine M.Raspovic eric Senneville Dane K.Wukich Nicolaas C.Schaper on behalf of the International Working Group on the Diabetic Foot 张会峰(译) 许樟荣(审校) Department of Rehabilitation Medicine Amsterdam UMCLocation University of AmsterdamAmsterdamthe Netherlands Amsterdam Movement Sciences Program RehabilitationAmsterdamthe Netherlands Department of Endocrinology University Hospital of MalmöMalmöSweden joondalup Health Campus Ramsay HealthcareSydneyAustralia Faculty of Health University of TasmaniaHobartAustralia School of Health Sciences Western Sydney UniversitySydneyAustralia Faculty of Health and Medical Sciences University of AdelaideAdelaideAustralia Vascular and Endovascular Service Royal Adelaide HospitalAdelaideAustralia Department of Diabetes and Endocrinology University Hospitals of Derby and Burton NHS Foundation TrustDerbyUK Department of Vascular Surgery University of BristolBristolUK School of Public Health and Social Work Queensland University of TechnologyBrisbaneAustralia Allied Health Research Collaborative The Prince Charles HospitalBrisbaneAustralia Michael E.DeBakey Department of Surgery Division of Vascular Surgery and Endovascular TherapyBaylor College of MedicineHoustonTexasUSA Portuguese Red Cross School of Health–Lisbon LisbonPortugal MEDCIDS–Departamento de Medicina da Comunidade Informação e Decisão em Saúde Faculty of Medicine of the University of PortoPortoPortugal RISE@CINTESIS Faculty of Medicine Oporto UniversityPortoPortugal Department of Internal Medicine Amsterdam UMCVrije Universiteit AmsterdamSection of Infectious DiseasesAmsterdamthe Netherlands Department of Orthopaedic Surgery University of Texas Southwestern Medical CenterDallasTexasUSA Department of Infectious Diseases Gustave Dron Hospital Tourcoing Univ-lilleTourcoingFrance Div.Endocrinology MUMC+CARIM and CAPHRI InstituteMaastrichtThe Netherlands 不详河南省人民医院内分泌科河南郑州450003 战略支援部队特色医学中心北京100101

糖尿病相关的足病管理涉及多个学科,通用的专业词汇对于各学科间准确沟通交流至关重要。国际糖尿病足工作组(IWGDF)对相关文献进行了系统综述,构成了制定IWGDF指南的基础,并且明确了糖尿病相关的足病的一系列定义、标准及名词解释。本... 详细信息

糖尿病相关的足病管理涉及多个学科,通用的专业词汇对于各学科间准确沟通交流至关重要。国际糖尿病足工作组(IWGDF)对相关文献进行了系统综述,构成了制定IWGDF指南的基础,并且明确了糖尿病相关的足病的一系列定义、标准及名词解释。本文介绍2023年IWGDF对这些定义和标准的更新,并建议在临床实践和研究中一致使用,以利于世界各地不同学科人员针对糖尿病相关的足病的专业性交流。

关键词：定义糖尿病糖尿病相关的足病国际糖尿病足工作组

Heat and drought impact on carbon exchange in an age-sequence of temperate pine forests

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Ecological Processes 2022年第1期11卷 108-125页

作者： M.Altaf Arain Bing Xu jason j.Brodeur Myroslava Khomik Matthias Peichl eric Beamesderfer Natalia Restrepo‑Couple Robin Thorne School of Earth Environment and Society and McMaster Centre for Climate ChangeMcMaster University1280 Main Street WestHamiltonON L8S 4K1Canada Department of Biological Sciences University of CalgaryAlbertaCanada Department of Geography and Environmental Management University of WaterlooWaterlooONCanada Department of Forest Ecology and Management Swedish University of Agricultural SciencesUmeåSweden School of Informatics Computingand Cyber SystemsNorthern Arizona UniversityFlagstaffAZUSA Department of Ecology and Evolutionary Biology University of ArizonaTucsonAZUSA Department of Geography Wilfrid Laurier UniversityWaterlooONCanada

Background:Most North American temperate forests are plantation or regrowth forests,which are actively *** forests are in different stages of their growth cycles and their ability to sequester atmospheric carbon is affected by extreme weather *** this study,the impact of heat and drought events on carbon sequestration in an age‑sequence(80,45,and 17 years as of 2019)of eastern white pine(Pinus strobus L.)forests in southern Ontario,Canada was examined using eddy covariance flux measurements from 2003 to ***:Over the 17‑year study period,the mean annual values of net ecosystem productivity(NEP)were 180±96,538±177 and 64±165 g C m^(–2)yr^(–1)in the 80‑,45‑and 17‑year‑old stands,respectively,with the highest annual carbon sequestration rate observed in the 45‑year‑old *** found that air temperature(Ta)was the dominant control on NEP in all three different‑aged stands and drought,which was a limiting factor for both gross ecosystem productivity(GEP)and ecosystems respiration(RE),had a smaller impact on ***,the simultaneous occurrence of heat and drought events during the early growing seasons or over the consecutive years had a significant negative impact on annual NEP in all three *** observed a similar trend of NEP decline in all three stands over three consecutive years that experienced extreme weather events,with 2016 being a hot and dry,2017 being a dry,and 2018 being a hot *** youngest stand became a net source of carbon for all three of these years and the oldest stand became a small source of carbon for the first time in 2018 since observations started in ***,in 2019,all three stands reverted to annual net carbon ***:Our study results indicate that the timing,frequency and concurrent or consecutive occurrence of extreme weather events may have significant implications for carbon sequestration in temperate conifer forests in Eastern North *** study is one of few globally available t

关键词： Carbon fluxes Net ecosystem productivity Ecosystem respiration Extreme weather events Drought Temperate forest White pine Eddy covariance

Disinfection byproducts in chlorinated or brominated swimming pools and spas: Role of brominated DBPs and association with mutagenicity

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journal of Environmental Sciences 2022年第7期34卷 253-263页

作者： Hannah K.Liberatore eric j.Daiber Sridevi A.Ravuri judith E.Schmid Susan D.Richardson David M.DeMarini Air Methods and Characterization Division Center for Environmental Measurement and ModelingU.S.Environmental Protection AgencyResearch Triangle ParkNC 27711USA Student Services Authority U.S.Environmental Protection AgencyNational Exposure Research LaboratoryAthensGA 30605USA National Health and Environmental Effects Research Laboratory U.S.Environmental Protection AgencyResearch Triangle ParkNC 27711USA Department of Chemistry and Biochemistry University of South CarolinaColumbiaSC 29208USA

Although the health benefits of swimming are well-documented, health effects such as asthma and bladder cancer are linked to disinfection by-products(DBPs) in pool water. DBPs are formed from the reaction of disinfectants such as chlorine(Cl) or bromine(Br) with organics in the water. Our previous study(Daiber et al., Environ. Sci. Technol. 50, 6652;2016) found correlations between the concentrations of classes of DBPs and the mutagenic potencies of waters from chlorinated or brominated swimming pools and spas. We extended this study by identifying significantly different concentrations of 21 individual DBPs in brominated or chlorinated pool and spa waters as well as identifying which DBPs and additional DBP classes were most associated with the mutagenicity of these waters. Using data from our previous study, we found that among 21 DBPs analyzed in 21 pool and spa waters, the concentration of bromoacetic acid was significantly higher in Brwaters versus Cl-waters, whereas the concentration of trichloroacetic acid was significantly higher in Cl-waters. Five Br-DBPs(tribromomethane, dibromochloroacetic acid, dibromoacetonitrile, bromoacetic acid, and tribromoacetic acid) had significantly higher concentrations in Br-spa versus Cl-spa waters. Cl-pools had significantly higher concentrations of ClDBPs(trichloroacetaldehyde, trichloromethane, dichloroacetic acid, and chloroacetic acid), whereas Br-pools had significantly higher concentrations of Br-DBPs(tribromomethane, dibromoacetic acid, dibromoacetonitrile, and tribromoacetic acid). The concentrations of the sum of all 4 trihalomethanes, all 11 Br-DBPs, and all 5 nitrogen-containing DBPs were each significantly higher in brominated than in chlorinated pools and spas. The 8 Br-DBPs were the only DBPs whose individual concentrations were significantly correlated with the mutagenic potencies of the pool and spa waters. These results, along with those from our earlier study, highlight the importance of Br-DBPs in the muta

关键词： Swimming pools Hot tubs Mutagenicity Disinfection byproducts Spas

Population-scale genetic control of alternative polyadenylation and its association with human diseases

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Quantitative Biology 2022年第1期10卷 44-54页

作者： Lei Li Yumei Li Xudong Zou Fuduan Peng Ya Cui eric j.Wagner Wei Li Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518055China Division of Computational Biomedicine Department of Biological ChemistrySchool of MedicineUniversity of CaliforniaIrvineCA 92697USA Department of Biochemistry&Molecular Biology University of Texas Medical BranchGalvestonTX 77555USA

Background:Genome-wide association studies(GWAS)have identified thousands of genomic non-coding variants statistically associated with many human traits and diseases,including ***,the functional interpretation of these non-coding variants remains a significant challenge in the post-GWAS *** polyadenylation(APA)plays an essential role in post-transcriptional regulation for most human *** employing different poly(A)sites,genes can either shorten or extend the 3'-UTRs that contain cu-regulatory elements such as miRNAs or RNA-binding protein binding ***,APA can affect the mRNA stability,translation,and cellular localization of ***-scale studies have revealed many inherited genetic variants that potentially impact APA to further influence disease susceptibility and phenotypic diversity,but systematic computational investigations to delineate the connections are in their earliest ***:Here,we discuss the evolving definitions of the genetic basis of APA and the modern genomics tools to identify,characterize,and validate the genetic influences of APA events in human *** also explore the emerging and surprisingly complex molecular mechanisms that regulate APA and summarize the genetic control of APA that is associated with complex human diseases and ***:APA is an intermediate molecular phenotype that can translate human common non-coding variants to individual phenotypic variability and disease susceptibility.

关键词： GWAS eQTL disease alternative polyadenylation

Gαq takes centre stage in multiple sclerosis pathogenesis

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Cellular & Molecular Immunology 2017年第5期14卷 401-402页

作者： eric j Downer School of Medicine Discipline of PhysiologyTrinity Biomedical Sciences Institute Trinity Col-lege Dublin Dublin 2 Ireland

There is no cure for multiple sclerosis （MS）; however, a number of strategies exist for disease management, including medications that reduce the frequency of relapses and long-term accrual of disability.1 However, the fact that MS therapies can be partially effective and have the risk of side effects, in addition to the observation that disability often continues to worsen despite immunotherapy, has highlighted the need for novel therapeutic targets in the disease.

关键词： Gαq centre stage multiple sclerosis