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World Journal of Gastroenterology 2015年第1期21卷 221-228页

作者： Florian Kuehn Ernst Klar anja bliemeister Michael Linnebacher Department of General ThoracicVascular and Transplantation SurgeryMolecular Oncology and ImmunotherapyUniversity of Rostock18057 RostockGermany

AIM: To analyze the cellular immune response towards microsatellite-instability(MSI)-induced frameshift-peptides(FSPs) in patients suffering from inflammatory bowel disease(IBD) with and without thiopurine-based immunosuppressive ***: Frequencies of peripheral blood T cell responses of IBD patients(n = 75) against FSPs derived from 14 microsatellite-containing candidate genes were quantified by interferon-γ enzyme-linked immunospot.T cells derived from 20 healthy individuals served as ***: Significant T cell reactivities against MSIinduced FSPs were observed in 59 of 75 IBD patients(78.7%).This was significantly more as we could observe in 20 healthy controls(P = 0.001).Overall,the reactivity was significantly influenced by thiopurine treatment(P = 0.032) and duration of disease(P = 0.002) but not by duration or cumulative amount of thiopurine therapy(P = 0.476).Unexpected,15 of 24(62.5%) IBD patients without prior thiopurine treatment also showed increased FSP-specific immune responses(P = 0.001).CONCLUSION: These findings propose FSPs as potential novel class of inflammation-associated antigens and this in turn may have implications for screening,diagnosis as well as clinical management of patients suffering from IBD and other inflammatory conditions.

关键词： Microsatellite-instability Inflammatory bowel dise

Is the speed of adjusting to environmental change condition dependent?An experiment with house mice(Mus musculus)

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Current Zoology 2024年第3期70卷 350-360页

作者： Karem Lopez-Hervas Neelam Porwal Mathilde Delacoux Alexandros Vezyrakis anja Guenther RG Behavioural Ecology of Individual Differences Max Planck Institute for Evolutionary Biology24306 PlönGermany Department of Evolutionary Biology Faculty of BiologyAdam Mickiewicz UniversityWieniawskiego 161-712 PoznańPoland Department for Collective Behaviour Max Planck Institute of Animal Behaviour78464 ConstanceGermany Centre for the Advanced Study of Collective Behaviour University of Konstanz78464 ConstanceGermany Animal Ecology Institute for Biochemistry and BiologyUniversity of Potsdam14469 PotsdamGermany

Environmental conditions change constantly either by anthropogenic perturbation or naturally across space and ***,a change in behavior is the frst response to changing *** fexibility can potentially improve an organism’s chances to survive and ***,we lack an understanding on the time-scale such behavioral adjustments need,how they actually affect reproduction and survival and whether behavioral adjustments are suffcient in keeping up with changing *** used house mice(Mus musculus)to test whether personality and life-history traits can adjust to an experimentally induced food-switch fexibly in adulthood or by intergenerational plasticity,that is,adjustments only becoming visible in the offspring *** lived in 6 experimental populations of semi-natural environments either on high or standard quality food for 4 *** showed previously that high-quality food induced better conditions and a less risk-prone ***,we tested whether the speed and/or magnitude of adjustment shows condition-dependency and whether adjustments incur ftness ***-history but not personality traits reacted fexibly to a food-switch,primarily by a direct reduction of reproduction and sloweddown *** whose parents received a food-switch developed a more active stress-coping personality and gained weight at a slower rate compared with their respective ***,the modulation of most traits was condition-dependent,with animals previously fed with high-quality food showing stronger *** study highlights that life-history and personality traits adjust at different speed toward environmental change,thus,highlighting the importance of the environment and the mode of response for evolutionary models.

关键词： animal personality context dependence environmental change Match-mismatch non-genetic inheritance phenotypic flexibility phenotypic plasticity

Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α

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Synthetic and Systems Biotechnology 2024年第3期9卷 416-424页

作者： Jeffrey L.Schloßhauer Lena Tholen Alexander Korner Stefan Kubick Sofia Chatzopoulou anja Honow Anne Zemella Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Faculty of Health Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnology Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational ***,toxic proteins and membrane proteins are often difficult-to-express in living ***,cell-free protein synthesis can be *** study explores innovative strategies for enhancing the production of challenging proteins through the modification of CHO cells by investigating both,cell-based and cell-free approaches.A major result in our study involves the integration of a mutant eIF2 translation initiation factor and T7 RNA polymerase into CHO cell lysates for cell-free protein *** resulted in elevated yields,while eliminating the necessity for exogenous additions during cell-free production,thereby substantially enhancing ***,we explore the potential of the Rosa26 genomic site for the integration of T7 RNA polymerase and cell-based tetracycline-controlled protein *** findings provide promising advancements in bioproduction technologies,offering flexibility to switch between cell-free and cell-based protein production as needed.

关键词： Inducible expression CHO cells Cell-free protein synthesis CRISPR T7 RNA polymerase eIF2 Rosa26

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

Role of homologous recombination/recombineering on human adenovirus genome engineering:Not the only but the most competent solution

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Engineering Microbiology 2024年第1期4卷 90-107页

作者： Lisa-Marie Dawson Montaha Alshawabkeh Katrin Schröer Fatima Arakrak anja Ehrhardt Wenli Zhang Virology and Microbiology Center for Biomedical Education and Research(ZBAF)School of MedicineFaculty of HealthWitten/Herdecke UniversityStockumer Str.1058453 WittenGermany

Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly ***,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector *** the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic *** review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these ***,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.

关键词： Adenoviral vector Gene therapy Homologous recombination Oncolytic virus Vaccine vector

Barriers and Motivators of Young Dutch Elite Athletes for Optimizing Their Nutritional Intake

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Open Journal of Preventive Medicine 2024年第7期14卷 143-162页

作者： Marijn de Wit anja van Geel Faculty of Nutrition & Dietetics The Hague University of Applied Sciences The Hague Netherlands Department of Sports Nutrition Papendal Arnhem Netherlands

Many young elite athletes do not meet their daily energy and nutrient requirements. However, little research has been done on why these athletes do not meet their daily needs. The aim was to research the barriers and motivators of young Dutch elite athletes to optimize their nutritional intake. Quantitative and qualitative research was conducted among 8 handball and 4 volleyball players at the Dutch National Sports Center (17.2 ± 0.8 years). First, the nutritional intake was tracked through food diaries and analyzed in Nutritics. Thereupon, five semi-structured interviews based on the COM-B model were carried out. The interviews were transcribed and coded. The athletes had a reduced intake of energy, carbohydrates, vitamins A, C, E, D, calcium, potassium, zinc, and iron compared to their requirements. Seven themes for optimizing their nutritional intake emerged in the interviews: needs assessment, practical translation, portion size, lack of time, involvement, individuality, and food distribution. Barriers that the athletes experienced were that they did not know what their total daily nutritional needs were and how this translates into practice. In addition, the portion size at dinner was too small. They also had little time to eat a full meal due to time pressure from training and school. On the other hand, motivators were receiving meal options to translate their needs into practice with a distribution of moments when they need to eat. Covering these topics in nutritional workshops where athletes actively participate with more individual focus, could contribute to the optimization of their nutritional intake.

关键词： Barriers Motivators Young Elite Athletes Optimize Nutritional Intake

Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

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World Journal of Gastroenterology 2024年第28期30卷 3418-3427页

作者： anja H W M Lemlijn-Slenter Karolina AP Wijnands Gijs van der Hamsvoort Luuk P van Iperen Nico Wolter Angelique E de Rijk Ad AM Masclee Department of Social Medicine Faculty of HealthMedicine and Life sciencesCare and Public Health Research Institute Maastricht UniversityMaastricht 6200 MDLimburgNetherlands Division of Gastroenterology and Hepatology Department of Internal MedicineSchool of Nutrition and Translational Research in MetabolismMaastricht 6200 MDLimburgNetherlands Social Medical Affairs Employee Insurance Agency(UWV)Heerlen 6400 ACLimburgNetherlands Department of Research Academic Knowledge Center Work and Health South-East Netherlands(AKAG-ZON)Heerlen 6400 ACLimburgNetherlands

BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of *** approach is especially relevant for patients with chronic *** gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ *** impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ *** To describe and quantify the dimensions of PH in patients with chronic GI-HPB *** Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical *** questionnaires and data from patient files were used to quantify the six dimensions of *** consistency was tested with McDonald’s ***-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered *** The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general *** quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB *** scores between the six dimensions were only very weak to weak,forcing us to quantify each domain *** All six dimensions of PH are impaired in the GI-HPB *** and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

关键词： Positive health Chronic gut disorders Gastrointestinal disorders Hepato-pancreatico-biliary disorders Integrated care

Hordedane diterpenoid phytoalexins restrict Fusarium graminearum infection but enhance Bipolaris sorokiniana colonization of barley roots

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Molecular Plant 2024年第8期17卷 1307-1327页

作者： Yaming Liu Dario Esposto Lisa K.Mahdi Andrea Porzel Pauline Stark Hidayat Hussain anja Scherr-Henning Simon Isfort Ulschan.Bathe Ivan F.Acosta Alga Zuccaro Gerd U.Balcke Alain Tissier Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryHalleGermany Institute for Plant Sciences Cluster of Excellence on Plant Sciences(CEPLAS)Cologne BiocenterUniversity of CologneCologneGermany Department of Bioorganic Chemistry Leibniz Institute of Plant BiochemistryHalleGermany Max Planck Institute for Plant Breeding Research CologneGermany Horticultural Sciences University of FloridaGainesvilleFLUSA.

Plant immunity is a multilayered process that includes recognition of patterns or effectors from pathogens to elicit defense *** include the induction of a cocktail of defense metabolites that typically restrict pathogen ***,we investigate the interaction between barley roots and the fungal pathogens Bipolaris sorokiniana(Bs)and Fusarium graminearum(Fg)at the metabolite *** identify hordedanes,a previously undescribed set of labdane-related diterpenoids with antimicrobial properties,as critical players in these *** of barley roots by Bs and Fg elicits hordedane synthesis from a 60o-kb gene *** reconstruction of the biosynthesis pathway in yeast and Nicotiana benthamiana produced several hordedanes,including one of the most functionally decorated products 19-β-hydroxy-hordetrienoic acid(19-OH-HTA).Barley mutants in the diterpene synthase genes of this cluster are unable to produce hordedanes but,unexpectedly,show reduced Bs *** contrast,colonization by Fusarium graminearum,another fungal pathogen of barley and wheat,is 4-fold higher in the mutants completely lacking ***,19-OH-HTA enhances both germination and growth of Bs,whereas it inhibits other pathogenic fungi,including *** of microscopy and transcriptomics data suggest that hordedanes delay the necrotrophic phase of *** together,these results show that adapted pathogens such as Bs can subvert plant metabolic defenses to facilitate root colonization.

关键词： barley Hordeum vulgare diterpenoid phytoalexins gene cluster pathogenic fungi Bipolaris sorokininiana Fusarium graminearum

Diagnostic delay in inflammatory bowel diseases in a German population

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World Journal of Gastroenterology 2024年第29期30卷 3465-3478页

作者： Elisabeth Blüthner Annalena Dehe Carsten Büning Britta Siegmund Matthias Prager Jochen Maul Alexander Krannich Jan Preiß Bertram Wiedenmann Florian Rieder Raneem Khedraki Frank Tacke Andreas Sturm anja Schirbel Department of Hepatology and Gastroenterology Campus Virchow-Klinikum and Campus CharitéMitteCharité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Vivantes Klinikum im FriedrichshainBerlin 10249Germany Department of Internal Medicine Krankenhaus WaldfriedeBerlin 14163Germany Department of Gastroenterology Infectious Diseases and RheumatologyCharité-Universitätsmedizin BerlinBerlin 12203Germany Praxis für Gastroenterologie Berlin Zehlendorf Berlin 14195Germany Gastroenterologie am Bayrischen Platz Berlin 10825Germany Clinical Trial Office Charité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Diabetology and HepatologyVivantes Klinikum NeuköllnBerlin 10117Germany Department of Gastroenterology Hepatology and NutritionDigestive Diseases and Surgery InstituteThe Cleveland Clinic FoundationClevelandOH 44195United States Department of Internal Medicine DRK Kliniken Berlin WestendBerlin 14050Germany Gastroenterologie im Havelland Straße der EinheitFalkensee 14612Germany

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients *** To identify risk factors leading to prolonged diagnostic time in a German IBD *** Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD *** diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time *** The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD *** UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic *** We demonstrated that CD patients compared to UC are at risk of long diagnostic *** efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

关键词： Diagnostic time Diagnostic delay Crohn’s disease Ulcerative colitis Germany

Adverse events related to physical restraint use in intensive care units: A review of the literature

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Journal of Intensive Medicine 2024年第3期4卷 318-325页

作者： Sebastian Berger Pascale Grzonka Simon A.Amacher Sabina Hunziker anja I.Frei Raoul Sutter Clinic for Intensive Care Department of Acute MedicineUniversity Hospital BaselBaselSwitzerland Medical Communication and Psychosomatic Medicine University Hospital BaselBaselSwitzerland Medical faculty University of BaselBaselSwitzerland Department of Clinical Research University of BaselBaselSwitzerland

Physical restraints are widely used and accepted as protective measures during treatment in intensive care unit (ICU). This review of the literature summarizes the adverse events and outcomes associated with physical restraint use, and the risk factors associated with their use during treatment in the ICU. The PubMed, Scopus, and Google Scholar databases were screened using predefined search terms to identify studies pertaining to adverse events and/or outcomes associated with physical restraint use, and the factors associated with their use in adult patients admitted to the ICU. A total of 24 articles (including 6126 patients) that were published between 2006 and 2022 were identified. The described adverse events associated with physical restraint use included skin injuries, subsequent delirium, neurofunctional impairment, and a higher rate of post-traumatic stress disorder. Subsequent delirium was the most frequent adverse event to be reported. No alternative measures to physical restraints were discussed, and only one study reported a standardized protocol for their use. Although physical restraint use has been reported to be associated with adverse events (including neurofunctional impairment) in the literature, the available evidence is limited. Although causality cannot be confirmed, a definite association appears to exist. Our findings suggest that it is essential to improve awareness regarding their adverse impact and optimize approaches for their detection, management, and prevention using protocols or checklists.

关键词： Physical restraint Intensive care unit Delirium Complication Adverse event