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Molecular Plant 2013年第6期6卷 1996-1999页

作者： judith katharina paulus, Christian Niehus Georg Groth Cluster of Excellence on Plant Sciences (CEPLAS) Institute of Biochemical Plant Physiology Heinrich Heine University Düsseldorf Germany

Dear Editor, Phosphoenolpyruvate carboxylase （PEPC） is the essential enzyme for initial carbon fixation in C4 photosynthesis. The C4-PEPC evolved from a non-photosynthetic C3 ancestor by subtle sequence changes resulting in distinctly different kinetic and regulatory characteristics （Svensson et al., 1997）. Malate and aspartate, which are formed from the carboxyla- tion product of PEPC, serve as feedback inhibitors of the PEPC （Wedding et al., 1990）. Higher malate or aspartate concen- trations during C4 photosynthesis require a reduced sensitiv- ity towards the feedback inhibitors of the C4-PEPC （Jacobs et al., 2008）.

关键词： Phosphoenolpyruvate carboxylase (PEPC) Inhibitor

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

Resolving the Activation Site of PositiveRegulators in Plant PhosphoenolpyruvateCarboxylase

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Molecular Plant 2014年第2期7卷 437-440页

作者： Daniel Schlieper Kerstin Förster judith K. paulus Georg Groth Institute of Biochemical Plant Physiology Cluster of Excellence on Plant Sciences (CEPLAS) Heinrich Heine University Düsseldorf 40204 Düsseldorf Germany

Dear Editor, Phosphoenolpyruvate carboxylase （PEPC; EC 4.***.1.31） islocated at an important branch point in the carbohydratemetabolism of plants. The enzyme is a homotetramer andcatalyzes the addition of bicarbonate to phosphoenolpyru-vate （PEP） to form oxaloacetate and phosphate. PEPC isregulated by metabolites and phosphorylation. AIIostericfeedback inhibition is mainly regulated by L-malate andL-aspartate which bind to a site separated from the activecenter （Kai et al., 1999; paulus et al., 2013）. Structure analy-sis of PEPC from Escherichia coli （Kai et al., 1999; Matsumuraet al., 2002）, Zea rnays （Matsumura et al., 2002）, Flaveria trin-ervia, and F. pringlei （paulus et al., 2013） revealed that thesubstrate PEP and the feedback inhibitors bind to separatesites within each monomer.

关键词： ZEA-MAYS MAIZE GLUCOSE-6-PHOSPHATE LEAVES

Bioactive glass based scaffolds coated with gelatin for the sustained release of icariin

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Bioactive Materials 2019年第1期4卷 1-7页

作者： Theresa Reiter Tanja Panick katharina Schuhladen judith A.Roether Jasmin Hum Aldo R.Boccaccini Institute of Biomaterials Department Materials Science and EngineeringUniversity of Erlangen-NurembergCauerstr.691058 ErlangenGermany

Gelatin-coated,3D sponge-like scaffolds based on 45S5 bioactive glass were produced using the foam replication *** strength tests of gelatin-coated samples compared to uncoated scaffolds showed significant strengthening and toughening effects of the gelatin coating with compressive strength values in the range of cortical ***,the crosslinked gelatin network(using either caffeic acid or N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride(EDC)/N-hxdroxysuccinimide(NHS)as crosslinking agent)was shown to be a suitable candidate for the sustained release of the bioactive molecule *** bioactivity of the produced scaffolds,characterization by FTIR and SEM indicated the formation of hydroxyapatite(HA)in all samples after immersion in simulated body fluid(SBF)for 14 days,highlighting the favorable combination of mechanical robustness,bioactivity and drug delivery capability of this new type of scaffolds.

关键词： Bioactive glass Icariin Drug release Gelatin Scaffold

Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 610-622,I0004-I0007页

作者： Magdalena Eilenberg Petra Munda judith Stift Felix BLanger Gerhard Prager Michael Trauner katharina Staufer Division of General Surgery Department of SurgeryMedical University of ViennaViennaAustria Department of Visceral Surgery and Medicine InselspitalUniversity Hospital BernBernSwitzerland Division of Gastroenterology&Hepatology Department of Internal Medicine IIIMedical University of ViennaViennaAustria Clinical Institute of Pathology Medical University of ViennaViennaAustria Division of Transplantation Department of SurgeryMedical University of ViennaViennaAustria

Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not been validated in severe to morbid *** study aimed at determining the accuracy of VCTE,CAP™and the composite score FibroScan-AST(FAST)in patients with a body mass index(BMI)of≥35 kg/m^(2).Methods:Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™measurement,and intraoperative liver *** feasibility and accuracy of VCTE,CAP™and the composite score FAST were retrospectively analysed to evaluate fibrosis,steatosis and active fibrotic non-alcoholic steatohepatitis[NASH+non-alcoholic fatty liver disease(NAFLD)activity score≥4+fibrosis grade≥2]using per protocol(PP)and intent to diagnose(ITD)***:In total,170 patients(median BMI 44.4 kg/m²)were included in the *** biopsy showed NASH,simple steatosis,and normal livers in 60.6%(n=103),28.8%(n=49),and 10.6%(n=18),*** and CAP™delivered reliable results in 90.6%(n=154/170)and 90.5%(n=134/148).The AUC(PP)of VCTE,CAP™,and FAST were 0.687(≥F2),0.786(≥F3),0.703(≥S2),0.738(S3),and 0.780(active fibrotic NASH).The AUC increased to 0.742(≥F2),0.842(≥F3),0.712(≥S2),0.780(S3),and 0.836(active fibrotic NASH)in patients below the median BMI of 44.4 kg/m².Conclusions:VCTE,CAP™and FAST show acceptable accuracy for the detection of fibrosis,steatosis and NASH in a real-life cohort of patients with *** improves in patients with a BMI44.4 kg/m^(2).

关键词： Transient elastography controlled attenuation parameter(CAP™) FibroScan-AST score(FAST score) obesity non-alcoholic fatty liver disease(NAFLD)

Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification

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Organic Chemistry Frontiers 2022年第6期9卷 1604-1615页

作者： Denis Dardić Nils Böhringer Alberto Plaza Florian Zubeil Juliane Pohl Svenja Sommer Leo Padva Jonathan Becker Maria A.Patras Mona-katharina Bill Michael Kurz Luigi Toti Sven W.Görgens Sören M.M.Schuler AndréBillion Oliver Schwengers paulus Wohlfart Alexander Goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann Till F.Schäberle Armin Bauer Fraunhofer Institute for Molecular Biology and Applied Ecology(IME) Branch for Bioresources35392 GießenGermany Justus-Liebig-University Gießen 35392 GießenGermany Sanofi-Aventis Deutschland GmbH R&D Integrated Drug Discovery65926 Frankfurt am MainGermany Sanofi-Aventis Deutschland GmbH R&D German Hub65926 Frankfurt am MainGermany German Center of Infection Research(DZIF) Partner Site Gießen-Marburg-Langen35392 GießenGermany

Seven new polyketides,termed veramycins,were isolated from a Streptomyces *** the Sanofi microbial strain collection along with their known congeners NFAT-133 and *** A,anα-pyrone congener of TM-123 and NFAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 GLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell *** syntheses of NFAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide *** approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NFAT-133 ***,the corresponding biosynthetic gene cluster(BGC)was identified by genome sequencing and gene *** on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis.

关键词： synthesis directed isomers