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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

Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions

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World Journal of Gastroenterology 2018年第38期24卷 4311-4329页

作者： elda Righi Department of Infectious Diseases Santa Maria della Misericordia University Hospital

Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early posttransplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa(P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.

关键词： Liver cirrhosis Liver transplant recipients Bacterial infections Fungal infections Multidrug resistant organisms Management

A Novel ABA Insensitive Mutant of Lotus japonicus with a Wilty Phenotype Displays Unaltered Nodulation Regulation

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Molecular Plant 2009年第3期2卷 487-499页

作者： Bandana Biswas pick Kuen Chan Peter M Gresshoff ARC Centre of Excellence for Integrative Legume Research The University of Queensland St Lucia Brisbane QId 4072 Australia

An ABA insensitive mutant, Beyma, was isolated in Lotus japonicus MG-20 from an EMS mutagenesis population using root growth inhibition to applied ABA as the screening criterion. （The name ＂Beyma＂ was taken from the Australian Aboriginal language, Wagiman, beyma, meaning ‘drying up＇.） The stable mutant that segregates as a dominant Mendelian mutation is insensitive to ABA induced inhibition of germination, vegetative growth, stomatal opening, as well as nodulation. Tissue ABA levels were normal, suggesting a sensitivity rather than biosynthesis mutation. It is slow-growing （50-70% of wild-type MG-20） and has a near-constitutive wilty phenotype associated with its inability to regulate stomatal opening. Whilst showing a wide range of ABA insensitive phenotypes, Beyma did not show alteration of nodule number control, as, in the absence of added ABA, the number and patterning （but not size） of nodules formed in the mutant were similar to that of MG-20. Split root experiments on MG-20 showed that application of ABA on one side of the root inhibited nodulation locally but not systemically. We propose that ABA is not involved directly in systemic autoregulation of nodulation （AON）.

关键词： hormone biology water relations genetics development symbiosis legume.

Classical Ethylene Insensitive Mutants of the Arabidopsis EIN2 Orthologue Lack the Expected‘hypernodulation’ Response in Lotus japonicus

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Journal of Integrative Plant Biology 2013年第4期55卷 395-408页

作者： pick Kuen Chan Bandana Biswas Peter M. Gresshoff Australian Research Council (ARC) Centre of Excellence for Integrative Legume Research The University of Queensland ARC Centre of Excellence for Integrative Legume Research and School of Agriculture and Food Sciences The University of Queensland

Three independent ethylene insensitive mutants were selected from an EMS- mutagenized population of Lotus japonicus MG-20 （Miyakojima）. The mutants, called ＇Enigma＇, were mutated in the LjEIN2a gene from Lotus chromosome 1, sharing significant homology with Arabidopsis EIN2 （ethylene-insensitive2）. All three alleles showed classical ethylene insensitivity phenotypes （e.g., Triple Response）, but lacked the increased nodulation phenotype commonly associated with ethylene insensitivity. Indeed, all showed a marginal reduction in nodule number per plant, a phenotype that is enigmatic to sickle, an ethylene- insensitive EIN2 mutant in Medicago truncatula. In contrast to wild type, but similar to an ETRI-1 ethylene ethylene-insensitive transgenic of L. japonicus, enigma mutants formed nodules in between the protoxylem poles, demonstrating the influence of ethylene on radial positioning. Suppression of nodule numbers by nitrate and colonisation by mycorrhizal fungi in the enigma-1 mutant were indistin- guishable from the wild-type MG-20. However, reflecting endogenous ethylene feedback, the enigma-1 mutant released more than twice the wild-type amount of ethylene, enigma-1 had a moderate reduction in growth, greater root mass （and lateral root formation）, delayed flowering and ripening, smaller pods and seeds. Expression analysis of ethylene-regulated genes, such as ETR1, NRL1 （neverripe-like 1）, and ElL3 in shoots and roots of enigma-1 and MG-20 illustrated that the ethylene-insensitive mutation strongly affected transcriptional responses in the root. These mutants open the possibility that EIN2 in L. japonicus, a determinate nodulating legume, acts in a more complex fashion possibly through the presence of a duplicated copy of LjEIN2.

关键词： ABA development ethylene legume nodulation symbiosis.

Comparative effects of plant growth regulators on leaf and stem explants of Labisia pumila var. alata

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第7期14卷 621-631页

作者： Anna pick Kiong LING Kinn Poay TAN Sobri HUSSEIN Division of Human Biology International Medical University Department of Science Faculty of Engineering and Science Universiti Tunku Abdul Rahman Agrotechnology and Bioscience Division Malaysian Nuclear Agency

Objective: Labisia pumila var. alata, commonly known as 'Kacip Fatimah' or 'Selusuh Fatimah' in Southeast Asia, is traditionally used by members of the Malay community because of its post-partum medicinal properties. Its various pharmaceutical applications cause an excessive harvesting and lead to serious shortage in natural habitat. Thus, this in vitro propagation study investigated the effects of different plant growth regulators (PGRs) on in vitro leaf and stem explants of L. pumila. Methods: The capabilities of callus, shoot, and root formation were evaluated by culturing both explants on Murashige and Skoog (MS) medium supplemented with various PGRs at the concentrations of 0, 1, 3, 5, and 7 mg/L. Results: Medium supplemented with 3 mg/L indole-3-butyric acid (IBA) showed the optimal callogenesis from both leaf and stem explants with (72.34±19.55)% and (70.40±14.14)% efficacy, respectively. IBA was also found to be the most efficient PGR for root induction. A total of (50.00±7.07)% and (77.78±16.47)% of root formation were obtained from the in vitro stem and leaf explants after being cultured for (26.5±5.0) and (30.0±8.5) d in the medium supplemented with 1 and 3 mg/L of IBA, respectively. Shoot formation was only observed in stem explant, with the maximum percentage of formation ((100.00±0.00)%) that was obtained in 1 mg/L zeatin after (11.0±2.8) d of culture. Conclusions: Callus, roots, and shoots can be induced from in vitro leaf and stem explants of L. pumila through the manipulation of types and concentrations of PGRs.

关键词： Auxin Cytokinin Labisia pumila In vitro propagation Plant growth regulators

Occurrence of retained placenta is preceded by an inflammatory state and alterations of energy metabolism in transition dairy cows

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Journal of Animal Science and Biotechnology 2016年第3期7卷 423-435页

作者： elda Dervishi Guanshi Zhang Dagnachew Hailemariam Suzana M.Dunn Burim N.Ametaj Department of Agricultural Food and Nutritional ScienceUniversity of Alberta

Background： Failure to expel fetal membranes within 24 h of calving is a pathological condition defined as retained placenta（RP）. The objective of this investigation was to evaluate whether there are alterations in several selected serum variables related to innate immunity and carbohydrate and lipid metabolism that precede occurrence of RP in transition Holstein dairy ***： One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected from the coccygeal vein during the-8 to ＋4 wks around parturition, once per week before the morning *** healthy control cows（CON） and 6 cows with RP were selected and serum samples at-8,-4, time of diagnosis of disease, and ＋4 wks relative to parturition were used for analyses. All samples were analyzed for lactate, nonesterified fatty acids（NEFA）, β-hydroxybutyrate（BHBA）, interleukin-1（IL-1）, interleukin-6（IL-6）, tumor necrosis factor（TNF）, haptoglobin（Hp）, and serum amyloid A（SAA）.Results： Cows with RP had greater concentrations of serum lactate, IL-1, IL-6, TNF, and SAA in comparison with CON cows. Intriguingly, elevated concentrations of all five variables were observed at-8 and-4 wks before the occurrence of RP compared to healthy cows. Cows with RP also had lower DMI and milk production vs CON animals; however milk composition was not affected by ***： Cows with RP showed an activated innate immunity 8 wks prior to diagnosis of disease. Overall results suggest that serum IL-1, IL- 6, and TNF, and lactate can be used as screening biomarkers to indicate cows that might have health issues during the transition period.

关键词： Innate immunity Retained placenta Serum metabolites Transition dairy cows

Towards the FAIRification of Scanning Tunneling Microscopy Images

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Data Intelligence 2023年第1期5卷 27-42页

作者： Tommaso Rodani elda Osmenaj Alberto Cazzaniga Mirco Panighel Cristina Africh Stefano Cozzini AREAScience Park Padriciano9934149TriesteItaly CNR-1OM Consiglio Nazionale delle Ricerche-Istituto Officina dei MaterialiS.S.14Km 163.5Basovizza34149TriesteItaly

In this paper,we describe the data management practices and services developed for making FAIR compliant a scientific archive of Scanning Tunneling Microscopy(STM)*** a first step,we extracted the instrument metadata of each image of the dataset to create a structured *** then enriched these metadata with information on the structure and composition of the surface by means of a pipeline that leverages human annotation,machine learning techniques,and instrument metadata *** visually explore both images and metadata,as well as to improve the accessibility and usability of the dataset,we developed"STM explorer"as a web service integrated within the Trieste Advanced Data services(TriDAS)*** top of these data services and tools,we propose an implementation of the W3C PROV standard to describe provenance metadata of STM images.

关键词： Provenance STM images data management FAIR metadata for nanoscience W3C PROV

Anti-neuroinflammatory responses in lipopolysaccharide-stimulated BV2 microglial cells upon treatment with methanol extract of Panax ginseng root

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Journal of Traditional Chinese Medicine 2021年第2期41卷 185-193页

作者： Chien Yi Koay Anna pick Kiong Ling Ying Pei Wong Rhun Yian Koh Sobri Hussein Division of Applied Biomedical Sciences and Biotechnology School of Health SciencesInternational Medical UniversityBukit JalilKuala Lumpur 57000Malaysia Department of Agrotechnology and Biosciences Malaysian Nuclear AgencyBangiKajang 43000SelangorMalaysia

OBJECTIVE:To investigate the anti-neuroinflammatory properties of Panax ginseng(***)root by measuring the levels of nitric oxide(NO),tumour necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)in lipopolysaccharide(LPS)-stimulated BV2 microglia ***:Maximal non-toxic dose(MNTD)of methanol extract of *** root culture on BV2 microglia cells was first determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,followed by treatment and LPS stimulation of cells,and the measurement of NO using Griess assay and TNF-α,IL-6,and IL-10 using ELISA ***:The MNTD of *** root extract was determined to be(587±57)µg/*** that,NO and IL-6 levels were found to be insignificantly reduced by 6.88%and 0.14%respectively in stimulated cells upon treatment with *** with½MNTD yielded similar insignificant result,with only a reduction of 3.58%and 0.08%in NO and IL-6 levels ***,TNF-αand IL-10 levels were significantly downregulated by 15.64%and 34.96%respectively upon treatment with *** root extract at ***:Methanol extract of *** root culture did not show any significant anti-inflammatory effects on NO and IL-6 levels,but might potentially possess both anti-neuroinflammatory and pro-neuroinflammatory properties through the downregulation of TNF-αand IL-10 respectively.

关键词： Panax Anti-inflammatory agents Cytokines Microglia Inflammation Root culture

Five-year longitudinal evaluation of quality of life in a cohort of patients with differentiated thyroid carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第3期12卷 163-173页

作者： Massimo GIUSTI Giulia MELLE Monica FENOCCHIO Lorenzo MORTARA Francesca CECOLI Valeria CAORSI Diego FERONE Francesco MINUTO elda RASORE Department of Endocrine and Medical Sciences University of Genoa Department of Psychiatric Sciences University of Genoa

Differentiated thyroid carcinoma(DTC) generally has a favorable *** disease,treatments,stress,and comorbidity can compromise health-related quality of life(QoL) and indirectly weigh upon the outcome. From 2004 to 2008,we evaluated QoL longitudinally in 128 DTC *** scheduled examinations,subjects were asked to undergo a semi-structured psychiatric interview and five rated *** same examination was conducted in 219 subjects after surgery for benign thyroid *** scores represent a better *** and control subjects were similar in terms of age,male/female ratio,concomitant psychopharmacological treatments,and frequency of psychiatric *** DTC subjects,Billewicz scale(BS) scores showed an increasing trend over time,especially among *** ad hoc thyroid questionnaire(TQ) scores were similar in both groups and did not change over time,but at the end of the study ad hoc TQ and BS were significantly *** hoc TQ scores were also related to age on entry to the *** both male and female DTC subjects,Hamilton's tests for anxiety(HAM-A) ,but not for depression(HAM-D),showed an improving *** the end of the study,HAM-A and HAM-D scores were comparable to those of the control ***-A and HAM-D were both positively correlated with the stage of cancer and the time between diagnosis and *** HAM-D correlated with age on entry to the *** symptom questionnaire(KSQ) item scores were higher in DTC subjects than in *** change over time in the items including anxiety,somatization,depression,and hostility was *** and hostility were more significantly reduced in DTC females than in DTC *** scores were significantly lower in DTC subjects than in controls at the end of the *** and depression were significantly related to staging on diagnosis and age on entry to the *** study confirms a wide variation of illness perception in DTC subjects

关键词： Thyroid cancer Outcome Psycholoqical evaluation Qualitv of life Loneitudinal study