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Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

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molecular Plant 2024年第5期17卷 824-837页

作者： Tom schreiber Anja Prange Petra schafer Thomas Iwen Ramona Grutzner Sylvestre marillonnet Aurelie Lepage marie Javelle Wyatt Paul Alain Tissier Department of Cell and metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Limagrain Centre de RechercheRoute d’EnnezatCS 9012663720 ChappesFrance

In plants and mammals,non-homologous end-joining is the dominant pathway to repair DNA doublestrand breaks,making it challenging to generate knock-in *** this study,we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana *** achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation *** Arabidopsis thaliana,fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of *** addition,we demonstrated stable and heritable knock-ins in wheat in 1%of the primary *** together,our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

关键词： homology-directed repair knockin gene replacement CRISPR-Cas 50 exonuclease plants

Degeneration of foundation cushion species induced by ecological constraints can cause massive changes in alpine plant communities

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Science China(Life Sciences) 2024年第4期67卷 789-802页

作者： Jianguo Chen Xufang Chen Lishen Qian Yazhou Zhang Bo Li Honghua Shi Lu Sun Christian schöb Hang Sun Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China College of Resources and Environment Yunnan Agricultural UniversityKunming 650500China Área de Biodiversidad y Conservación Universidad Rey Juan CarlosMóstoles 28933Spain

Foundational cushion plants can re-organize community structures and sustain a prominent proportion of alpine biodiversity,but they are sensitive to climate *** loss of cushion species can have broad consequences for associated *** potential plant community changes with the population dynamics of cushion plants remain,however,*** eight plant communities along a climatic and community successional gradient,we assessed cushion population dynamics,the underlying ecological constraints and hence associated plant community changes in alpine communities dominated by the foundational cushion plant Arenaria *** population dynamics of Arenaria are attributed to ecological constraints at a series of life history *** functions are constrained by increasing associated beneficiary plants;subsequent seedling establishment is constrained by temperature,water and light availability,extreme climate events,and interspecific competition;strong competitive exclusion may accelerate mortality and degeneration of cushion *** with cushion dynamics,species composition,abundance and community structure gradually *** cushion plants completely degenerate,previously cushion-dominated communities shift to relatively stable communities that are overwhelmingly dominated by *** warming may accelerate the degeneration process of *** of this foundational cushion plant will possibly induce massive changes in alpine plant communities and hence ecosystem functions in alpine *** assessment of the population dynamics of foundation species is critical for an effective conservation of alpine biodiversity.

关键词： alpine ecosystem biodiversity change climate change plant community dynamics foundation species global warming population dynamics

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Removal of endocrine disrupting chemicals from water through urethane functionalization of microfiltration membranes via electron beam irradiation

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 61-74页

作者： Zahra Niavarani Daniel Breite muhammad Yasir Vladimir Sedlarik Andrea Prager Nadja schönherr Bernd Abel Roger Gläser Agnes schulze Leibniz Institute of Surface Engineering eV.(IOm) Permoserstrasse 1504318 LeipzigGermany Centre of Polymer Systems University InstituteTomas Bata University in ZlinTrida Tomase Bati 567876001 ZlinCzech Republic Institute of Chemical Technology Leipzig UniversityLinnestrasse 304103 LeipzigGermany

Polyethersulphone(PES)membranes modified with urethane functional groups were prepared through an interfacial reaction using electron beam *** removal of eight endocrine disrupting chemicals(EDCs)was studied using both pristine and functionalized PES *** prepared membranes underwent characterization using several techniques,including attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy,scanning electron microscopy,contact angle analysis,and measurements of pure water ***,dynamic adsorption experiments were conducted to evaluate the adsorption mechanism of the prepared membrane toward the eight *** urethane functionalized membranes were hydrophilic(52°contact angle)and maintained a high permeate flux(26000 L/h m^(2) bar)throughout the filtration *** adsorption results demonstrated that the introduction of urethane functional groups on the membranes significantly enhanced the removal efficiency of 17β-estradiol,estriol,bisphenol A,estrone,ethinylestradiol,and *** adsorption loading of 17β-estradiol on the functionalized PES membrane was 6.7±0.7 mg/m^(2),exhibiting a 5-fold increase compared to the unmodified PES *** membranes were successfully regenerated and reused for three adsorption cycles without experiencing any loss of adsorption capacity.

关键词： Surface functionalization Electron beam irradiation microfiltration Endocrine disrupting chemicals

Remains of the day:Biliary complications related to single-port laparoscopic cholecystectomy

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World Journal of Gastroenterology 2014年第3期20卷 843-851页

作者： Pierre Allemann Nicolas Demartines markus schfer Department of Visceral Surgery University Hospital CHUV

AIm: To assesse the rate of bile duct injuries (BDI) and overall biliary complications during single-port laparoscopic cholecystectomy (SPLC) compared to conventional laparoscopic cholecystectomy (CLC).

关键词： Bile ducts Cholecystectomy Single port Single incision

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene schnorr Angela schulz martina Strnadová Akhil Velluva Heba Zabri Torsten schöneberg Doreen Thor Simone Prömel Rudolf schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany school of medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(mC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

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World Journal of Gastroenterology 2005年第12期11卷 1769-1774页

作者： michael R Kraus Arne sch(a|¨)fer Herbert Csef michael scheurlen medizinische Poliklinik

AIm: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional ***: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98patients; 5 mIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μgpeginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).RESULTS: Therapy with pegylated interferon alfa-2bproduces comparable scores for depression (ANOVA:P = 0.875) as compared to conventional *** of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy ***: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

关键词： Pegylated interferon Hepatitis C Side effects Depression Interferon alfa

Thermophysical properties of the Ni-based alloy Nimonic 80A up to 2400 K

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Rare metals 2006年第5期25卷 529-531页

作者： B.Wilthan R.Tanzer W.schützenhfer G.Pottlacher Institute of Experimental Physics Graz University of TechnologyPetersgasse 168010 GrazAustria Bhler Edelstahl GmbH Mariazellerstrasse 258605 KapfenbergAustria

Nimonic 80A is a nickel-chromium alloy which is strengthened by additions of titanium and aluminium. The alloy is used for high temperature, high strength applications. Wire shaped Nimonic 80A samples are resistively volume heated as part of a fast capacitor discharge circuit. Time resolved measurements with sub-μs resolution of current through the specimen are performed with a Pearson probe, voltage drop across the specimen is measured with knife-edge contacts and ohmic voltage dividers and the radiance temperature of the sample with a pyrometer. These measurements allow to determine heat of fusion as well as heat capacity and electrical resistivity at initial geometry of Nimonic 80A as a function of temperature in the solid and in the liquid phase up to 2400 K.

关键词： thermophysical properties Nimonic 80A resistivity enthalpy heat capacity latent heat

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Accurate energy barriers for catalytic reaction pathways: an automatic training protocol for machine learning force fields

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npj Computational materials 2023年第1期9卷 479-488页

作者： Lars L.schaaf Edvin Fako Sandip De Ansgar schäfer Gábor Csányi Engineering Laboratory University of CambridgeCB21PZ CambridgeUK BASF SE Carl-Bosch-Straße 3867056 LudwigshafenGermany

We introduce a training protocol for developing machine learning force fields(mLFFs),capable of accurately determining energy barriers in catalytic reaction *** protocol is validated on the extensively explored hydrogenation of carbon dioxide to methanol over indium *** the help of active learning,the final force field obtains energy barriers within 0.05 eV of Density Functional *** to the computational speedup,not only do we reduce the cost of routine in-silico catalytic tasks,but also find an alternative path for the previously established rate-limiting step,with a 40%reduction in activation ***,we illustrate the importance of finite temperature effects and compute free energy *** transferability of the protocol is demonstrated on the experimentally relevant,yet unexplored,top-layer reduced indium oxide *** ability of mLFFs to enhance our understanding of extensively studied catalysts underscores the need for fast and accurate alternatives to direct ab-initio simulations.

关键词： surface catalytic fields

核苷二磷酸激酶C抑制人心力衰竭时的环磷酸腺苷生成

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中华高血压杂志 2017年第1期25卷 26-26页

作者：刘莉叶鹏 Abu-Taha IH Heijman J Hippe HJ Wolf Nm El-Armouche A Nikolaev VO sch?fer m Würtz C Neef S Voigt BaczkóI Varró A müller m meder B Katus HA Spiger K Vettel C Lehmann LH Backs J Skolnik EY Lutz S Dobrev D Wieland T

慢性心力衰竭（chronic heart failure，CHF）与β肾上腺素受体／G蛋白耦联受体信号转导系统变化、环磷酸腺苷（cyclic adenosine monophosphate，cAmP）生成减少相关。核苷酸磷酸激酶（nucleoside diphosphate kinases，NDPK）在终末期... 详细信息

慢性心力衰竭（chronic heart failure，CHF）与β肾上腺素受体／G蛋白耦联受体信号转导系统变化、环磷酸腺苷（cyclic adenosine monophosphate，cAmP）生成减少相关。核苷酸磷酸激酶（nucleoside diphosphate kinases，NDPK）在终末期CHF患者的血浆质膜富集，但其功能在很大程度上是未知的，

关键词：慢性心力衰竭环磷酸腺苷磷酸激酶C 核苷酸 G蛋白耦联受体 β肾上腺素受体 kinases 信号转导系统

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