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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam jochen h.m.prehn hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China mOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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The transcriptional landscape of the developmental switch from regular pollen maturation towards microspore-derived plant regeneration in barley

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The Crop Journal 2024年第4期12卷 1064-1080页

作者： Anna Nowicka martin Kovacik Anna maksylewicz Przemysław Kopec Ewa Dubas monika Krzewska Agnieszka Springer Robert E.hoffie Diaaeldin S.Daghma Zbynek milec Ales Pecinka jochen Kumlehn Iwona Zur The Franciszek Górski Institute of Plant Physiology Polish Academy of Sciences Niezapominajek 2130-239 KrakówPoland Institute of Experimental Botany of the Czech Academy of Sciences Centre of Plant Structural and Functional GenomicsŠlechtitelu3177900 OlomoucCzech Republic Department of Cell Biology and Genetics Faculty of SciencePalacky UniversityŠlechtitelu°2777900 OlomoucCzech Republic malopolska Centre of Biotechnology Jagiellonian University30-387 KrakówPoland Leibniz Institute of Plant Genetics and Crop Plant Research(IPK)Gatersleben Corrensstraße 306466 Stadt SeelandGermany Institute for Breeding Research on horticultural Crops Julius Kühn Institute(JKI)-Federal Research Centre for Cultivated PlantsErwin-Baur Straße 2706484 QuedlinburgGermany Global Change Research Institute Czech Academy of Sciences Beˇlidla 986/4a60300 BrnoCzech Republic

Plant formation from in vitro-cultivated microspores involves a complex network of internal and environmental ***/doubled haploids(Dhs)derived from in vitro-cultured microspores are widely used in plant breeding and genetic ***,the mechanism underlying the developmental switch from regular pollen maturation towards microspore-derived plant regeneration remains poorly ***,RNA-sequencing was employed to elucidate the transcriptional landscapes of four early stages of microspore embryogenesis(mE)in barley cultivars Golden Promise and Igri,which exhibit contrasting responsiveness to microspore-derived plant *** experiments revealed fundamental regulatory networks,specific groups of genes,and transcription factor(TF)families potentially regulating the developmental *** identified a set of candidate genes crucial for genotype-dependent responsiveness/recalcitrance to *** high-resolution temporal transcriptome atlas provides an important resource for future functional studies on the genetic control of microspore developmental transition.

关键词： hordeum vulgare marker gene microspore embryogenesis Stress response Transcriptome analysis

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The Drought of Amazonia in 2023-2024

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American Journal of Climate Change 2024年第3期13卷 567-597页

作者： Jose A. marengo Ana P. Cunha Jhan-Carlo Espinoza Rong Fu jochen Schöngart Juan C. Jimenez mabel C. Costa Joao m. Ribeiro Sly Wongchuig Siyu Zhao National Center for monitoring and Early Warning of Natural Disasters/CEmADEN So Jos dos Campos Brazil UNESP/CEmADEN So Jos dos Campos Brazil Graduate School of International Studies Korea University Seoul South Korea Institut des Gosciences de lEnvironnement (IGE) Institut de Recherche pour le Dvelopement (IRD) Saint Martin dHeres France Instituto de Investigacin sobre la Enseanza de las matemticas (IREm PUCP) Pontificia Universidad Catlica del Per Lima Peru Department of Atmospheric and Oceanic Sciences University of California Los Angeles Los Angeles CA USA Departament of Environmental Dynamics Instituto Nacional de Pesquisas da Amaznia (INPA) Manaus Brazil Global Change Unit (GCU) of the Image Processing Laboratory (IPL) Universitat de Valncia Estudi General (UVEG) Paterna Spain Laboratoire dEtudes en Gophysique et Ocanographie Spatiales (LEGOS) Universit de Toulouse CNES/CNRS/IRD/UT3 Toulouse France

The Amazon basin has experienced an extreme drought that started in the austral summer of 2022-23 and extends into 2024. This drought started earlier than other previous droughts. Although some rain fell during the austral summer, totals remained below average. higher temperatures during austral winter and spring 2023, which affected most of Central South America, then aggravated drought conditions. This coincided with an intense El Niño and abnormally warm tropical North Atlantic Ocean temperatures since mid-2023. Decreased rainfall across the Amazon basin, negative anomalies in evapotranspiration (derived from latent heat) and soil moisture indicators, as well as increased temperatures during the dry-to-wet transition season, September-October-November (SON) 2023, combined to delay the onset of the wet season in the hydrological year 2023-24 by nearly two months and caused it to be uncharacteristically weak. SON 2023 registered a precipitation deficit of the order of 50 to 100 mm/month, and temperatures +3˚C higher than usual in Amazonia, leading to reduced evapotranspiration and soil moisture indicators. These processes, in turn, determined an exceptionally late onset and a lengthening of the dry season, affecting the 2023-2024 hydrological year. These changes were aggravated by a heat wave from June to December 2023. Drought-heat compound events and their consequences are the most critical natural threats to society. River levels reached record lows, or dried up completely, affecting Amazonian ecosystems. Increased risk of wildfires is another concern exacerbated by these conditions.

关键词： El Niño SST in the Tropical Atlantic Amazon Drought River Levels heatwave Dry Season Length

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Effects of grassland management, endophytic fungi and predators on aphid abundance in two distinct regions

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Journal of Plant Ecology 2014年第5期7卷 490-498页

作者： Carmen Börschig Alexandra-m.Klein jochen Krauss Agroecology Department of Crop SciencesUniversity of GöttingenGrisebachstrasse 6D-37075 GöttingenGermany Ecosystem Functions Institute of EcologyUniversity of LüneburgScharnhorstrasse 1D-21335 LüneburgGermany Nature Conservation and Landscape Ecology Institute of Earth and Environmental SciencesUniversity of FreiburgTennenbacherstr.4D-79106 FreiburgGermany Department of Animal Ecology and Tropical Biology University of WürzburgBiocentreAm HublandD-97074 WürzburgGermany

Aims Fungal endophytes of cool-season grass species produce alkaloids toxic to herbivores,affecting food webs in agricultural and natural *** studies about the effects of endophytes on herbi-vores are rare and show contradictory results,leading to uncertain conclusions about the nature of endophyte-grass *** asked whether the environmental contexts of local and regional scales and predation could modify the effects of endophytes on *** In a full factorial field experiment,we quantified the abundance of the aphid species Rhopalosiphum padi on the potted host grass Lolium perenne,which was either infected or uninfected with the endophytic fungus Neotyphodium *** were either excluded or had free access to the pots with the *** hun-dred and sixty grass pots were located in two regions on altogether 40 grassland sites,half of the sites intensively and half extensively *** tested the importance of endophyte infection,study region,management intensity of grasslands,predation and all two-way interactions on aphid *** Findings Endophyte infection reduced aphid abundance significantly in one study region *** both regions,we found that the impacts of aphidophagous predators and grassland management intensity on aphid abundance were substantially stronger and more consistent than that of endophytes on aphid *** excluding preda-tors and pots placed on extensive grasslands contained higher aphid *** impact of predators and management on aphid abundance were not modified by the *** conclude that the effect of endophytes on herbivores can be weak in field experi-ments and depends on environmental context at a regional ***,more field research efforts are necessary to detect the rela-tive importance of endophytes and the environmental context on biotic interactions in ecosystems.

关键词： bottom-up control microorganism multi-trophic interaction predator exclosure top-down control

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Transplantation of an eight-organ multivisceraI graft in a patient with frozen abdomen after complicated Crohn's disease

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World Journal of Gastroenterology 2006年第27期12卷 4431-4434页

作者： Andreas Pascher jochen Klupp Sven Kohler Jan m Langrehr Peter Neuhaus Department of Visceral and Transplantation Surgery Charité-Universittsmedizin BerlinCampus Virchow KlinikumAugustenburgerplatz 1Berlin 13353Germany Exploratory Clinical Development Novartis Pharma AGWSJ-103.4.26CH-4002 BaselSwitzerland

To report an extended multivisceral transplantation （mVTx） including right kidney and ascending colon in a patient with complicated Crohn＇s disease （CD）. A 36-year old female suffering from short bowel syndrome and frozen abdomen due to fistulizing CD after multiple abdominal operations underwent mVTx of eight organs including stomach, pancreatoduodenal complex, liver, intestine, ascending colon, right kidney, right adrenal gland, and greater omentum in November 2003. Immunosuppression consisted of alemtuzumab, tacrolimus and steroids. The patient was off parenteral nutrition by postoperative wk 3. She experienced one episode of pneumonia. The patient recovered completely and discharged 2.5 mo and was doing well 30 mo after mVTx. This is one of the very rare cases in which a complete mulitivisceral graft of eight abdominal organs was transplanted orthotopically.

关键词： multivisceral transplantation Intestinal transplantation Crohn's disease

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Improvement of the Corrosion Resistance of high Alloyed Austenitic Cr-Ni-mo Stainless Steels by Solution Nitriding

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材料热处理学报 2004年第5期25卷 316-321页

作者： Christine Eckstein heinz- Joachim Spies jochen Albrecht Dept. of materials Eng. Technische Universitat Bergakademie Freiberg 09599 Freiberg/GermanyDept. of Materials Eng. Technische Universitat Bergakademie Freiberg 09599 Freiberg/GermanyInstitut Fresenius GmbH Solid State Analytic Zur Wetterwarte 10Haus 107 01109 Dresden Germany

Characteristic features of austenitic steel grades combine a good corrosion resistance with a low hardness, wear resistance and scratch resistance. An interesting possibility for improving the wear behaviour of these steels without loss of their corrosion resistance lies in enriching the near surface region with nitrogen. The process of a solution nitriding allows the rise of the solution of nitrogen in the solid phase. On this state nitrogen increases the corrosion resistance and the tribilogical load-bearing capacity. The aim of the study was, to investigate the improvement of the pitting corrosion behaviour by solution nitriding. A special topic was to observe the effect of nitrogen by different molybdenum content. So austenitic stainless steels (18% Cr, 12% Ni, mo gradation between 0.06 to 3.6%) had been solution nitrided. The samples could be prepared with various surface content of nitrogen from 0.04 to 0.45% with a step-by-step grinding. The susceptibility against pitting corrosion of these samples had been tested by determination of the stable pitting potential in 0.5m and 1m NaCl at 25°C. For the investigated steel composition and the used corrosion system there is no influence of molybdenum on the effectiveness of nitrogen. The influence of nitrogen to all of the determined parameters can be described well by PRE = Cr + 3,3 * mo + 25 *N. XPS analysis of the sample surfaces support the results of the pitting corrosion *** surface investigations with an acid elektolyte (0,1m hC1 + 0,4m NaCl) were performed. In this case the passivation effective nitrogen content increases markedly with rising molybdenum concentration of the steel. Obviously an interaction of mo and N is connected with a strongly acid electrolyte.

关键词：耐蚀性奥氏体不锈钢 Cr-Ni-mo 渗氮 PRE 稳定点蚀电位

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Intestinal eosinophils:characterization of elusive granulocytes as anti-bacterial and immunomodulatory effector cells in colitis

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3904-3906页

作者： Tim holland jochen mattner mikrobiologisches Institut-Klinische mikrobiologie Immunologie und HygieneUniversitätsklinikum Erlangen and Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergErlangenGermany medical Immunology Campus Erlangen FAU Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combination of human singe cell transcip-tomics with pre-clinical experimental studies,the authors suggest eosinophils as promising targets for clinical intervention in inflammatory bowel disease(IBD).Eosinophils are known to exhibit versatile functions at mucosal ***,they can sustain the intestinal epithelial barrier as well as intestinal tissue architecture,communicate with other cell subsets and regulate local immune responses.2 however,despite having been associated with a panoply of different diseases including eosinophilic esophagitis or IBD,3 their role and plasticity in gastrointestinal disorders have not been well characterized.

关键词： eosinophils clinical diseases

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Adjusting the physico-chemical properties of collagen scaffolds to accommodate primary osteoblasts and endothelial cells

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Regenerative Biomaterials 2023年第1期10卷 590-602页

作者： Nima meyer Daniel V.Bax jochen Beck Ruth E.Cameron Serena m.Best Department of materials Science and metallurgy University of CambridgeCambridge CB30FSUK Geistlich Pharma AG Product DevelopmentWolhusenSwitzerland

Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural *** regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and,where angiogenesis is intended,endothelial *** it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell *** work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast(hOBs)and human dermal microvascular endothelial cells(hDmECs)to insoluble collagen-based *** behaviour was evaluated on both 2D films and 3D scaffolds,produced using *** collagen was cross-linked at various EDC/NhS concentrations and mono-cultured with hOBs and hDmECs to assess the effect of architectural features and scaffold stabilization on cell *** was observed that 3D scaffolds cross-linked at 30%of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types,although endothelial cells were more sensitive to the degree of cross-linking than *** features have a time-dependent impact on the cell migration profile,with alignment being the most influential parameter overall.

关键词： angiogenesis collagen scaffolds cell migration EDC/NhS cross-linking

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Resolution of acute gastroenteritis symptoms in children and adults treated with a novel polyphenol-based prebiotic

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World Journal of Gastroenterology 2014年第34期20卷 12301-12307页

作者： Telma Noguera Robert Wotring Chris R melville Kara hargraves jochen Kumm John m morton Instituto Centroamericano de Investigación Clínica Managua 050-008-4Nicaragua Greenteaspoon Inc StanfordCA 94305United States Department of Biology Stanford UniversityStanfordCA 94305United States Bariatric and minimally Invasive Surgery Stanford School of MedicineStanfordCA 94305United States

AIm: To test efficacy and durability of a polyphenol-based prebiotic treatment for acute gastroenteritis in a 300 patient double-blinded clinical study.

关键词： Prebiotic Gastroenteritis Diarrhea Rotavirus Infant mortality Dehydration heartburn Polyphenol Aliva Greenteaspoon

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Polychlorinated biphenyls (PCBs), hexabromocyclododecanes (hBCDDs) and degradation products in topsoil from Australia and the United Kingdom

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Emerging Contaminants 2016年第1期2卷 37-41页

作者： Jennifer Desborough Timothy Evans jochen müller Stuart harrad School of Geography Earthand Environmental SciencesUniversity of BirminghamBirmingham B152TTUnited Kingdom National Research Centre for Environmental Toxicology(Entox) The University of Queensland39 Kessels RoadBrisbaneQueensland 4108Australia

hexabromocyclododecane(hBCDD)is listed under the Stockholm Convention on persistent organic pollutants,yet very few data are available on hBCDD concentrations in *** concentrations of total hexabromocyclododecanes(ShBCDDs)from soils from the UK(n=24)were 0.73 ng g^-1 dry weight(rangehose in Australian soils(n=17,median=0.10 ng g^-1,rangehlorinated biphenyls(PCBs)(average=4.7 ng SPCBs g^-1,range=0.39-21 ng g^-1)were determined in 19 UK samples and found to be statistically indistinguishable(p>0.05)from those of hBCDDs;thereby underlining the extent to which hBCDDs have migrated into the UK ***,PCB concentrations in this study are not markedly lower than those recorded in UK soils sampled in the mid-1980s indicating that the initial rapid decline in UK contamination with PCBs following bans on their manufacture and use,has not been *** products of hBCDD:pentabromocyclododecenes(PBCDs)and tetrabromocyclododecadienes(TBCDs)were detected in some UK soil samples with semi-quantitative concentrations ranging between 0.01 and 7.3 ng g^-1 for SPBCDs and 0.01e1.3 ng g^-1 for *** Australian soils only STBCDs were detected at concentrations ranging from 0.0023 to 0.45 ng g^-*** signatures of hBCDDs were racemic or non-racemic in all samples indicating minimal edaphic enantioselective degradation.A horizontal transect at the most contaminated UK location(a suburban garden)revealed a marked decrease in concentrations of hBCDDs with increasing distance from buildings.

关键词： Soil BFRs POPs Chiral signatures Enantiomer fractions

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