Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen

BACKGROUND: The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. METHODS: Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6) were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8) and 48 hours (n = 8) after the first injection and at the end of the whole treatment (n = 7). RESULTS: The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours) and amylase (after 48 hours) were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls. CONCLUSION: The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas

Evidence for increasing global wheat yield potential

Wheat is the most widely grown food crop, with 761 Mt produced globally in 2020. To meet the expected grain demand by mid-century, wheat breeding strategies must continue to improve upon yield-advancing physiological traits, regardless of climate change impacts. Here, the best performing doubled haploid (DH) crosses with an increased canopy photosynthesis from wheat field experiments in the literature were extrapolated to the global scale with a multi-model ensemble of process-based wheat crop models to estimate global wheat production. The DH field experiments were also used to determine a quantitative relationship between wheat production and solar radiation to estimate genetic yield potential. The multi-model ensemble projected a global annual wheat production of 1050 ± 145 Mt due to the improved canopy photosynthesis, a 37% increase, without expanding cropping area. Achieving this genetic yield potential would meet the lower estimate of the projected grain demand in 2050, albeit with considerable challenges.Fil: Guarin, Jose Rafael. National Aeronautics and Space Administration; Estados Unidos. Columbia University; Estados Unidos. Florida State University; Estados UnidosFil: Martre, Pierre. Institut Agro Montpellier SupAgro; FranciaFil: Ewert, Frank. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Webber, Heidi. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Dueri, Sibylle. Institut Agro Montpellier SupAgro; FranciaFil: Calderini, Daniel Fernando. Universidad Austral de Chile; ChileFil: Reynolds, Matthew. International Maize and Wheat Improvement Center ; MéxicoFil: Molero, Gemma. KWS; FranciaFil: Miralles, Daniel Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Garcia, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Slafer, Gustavo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universitat de Lleida; España. Institució Catalana de Recerca i Estudis Avancats; EspañaFil: Giunta, Francesco. Consiglio Nazionale Delle Ricerche. Istituto Di Scienze Dell Atmosfera E del Clima.; ItaliaFil: Pequeno, Diego N.L.. International Maize and Wheat Improvement Center; MéxicoFil: Stella, Tommaso. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Ahmed, Mukhtar. University Of Pakistan; PakistánFil: Alderman, Phillip D.. Oklahoma State University; Estados UnidosFil: Basso, Bruno. Michigan State University; Estados UnidosFil: Berger, Andres G.. Instituto Nacional de Investigacion Agropecuaria;Fil: Bindi, Marco. Università degli Studi di Firenze; ItaliaFil: Bracho-Mujica, Gennady. Universität Göttingen; AlemaniaFil: Cammarano, Davide. Purdue University; Estados UnidosFil: Chen, Yi. Chinese Academy of Sciences; República de ChinaFil: Dumont, Benjamin. Université de Liège; BélgicaFil: Rezaei, Ehsan Eyshi. Leibniz Institute Of Plant Genetics And Crop Plant Research.; AlemaniaFil: Fereres, Elias. Universidad de Córdoba; EspañaFil: Ferrise, Roberto. Michigan State University; Estados UnidosFil: Gaiser, Thomas. Universitat Bonn; AlemaniaFil: Gao, Yujing. Florida State University; Estados UnidosFil: Garcia Vila, Margarita. Universidad de Córdoba; EspañaFil: Gayler, Sebastian. Universidad de Hohenheim; Alemani

Evidence for increasing global wheat yield potential

Wheat is the most widely grown food crop, with 761 Mt produced globally in 2020. To meet the expected grain demand by mid-century, wheat breeding strategies must continue to improve upon yield-advancing physiological traits, regardless of climate change impacts. Here, the best performing doubled haploid (DH) crosses with an increased canopy photosynthesis from wheat field experiments in the literature were extrapolated to the global scale with a multi-model ensemble of process-based wheat crop models to estimate global wheat production. The DH field experiments were also used to determine a quantitative relationship between wheat production and solar radiation to estimate genetic yield potential. The multi-model ensemble projected a global annual wheat production of 1050 +/- 145 Mt due to the improved canopy photosynthesis, a 37% increase, without expanding cropping area. Achieving this genetic yield potential would meet the lower estimate of the projected grain demand in 2050, albeit with considerable challenges

Outcome of Colorectal Cancer Patients Treated with Combination Bevacizumab Therapy: A Pooled Retrospective Analysis of Three European Cohorts from the Angiopredict Initiative

Background/Aims: This study is aimed at analyzing the survival rates and prognostic factors of stage IV colorectal cancer patients from 3 European cohorts undergoing combination chemotherapy with bevacizumab. Methods: Progression free-survival (PFS) and overall survival (OS) were analyzed in 172 patients using the Kaplan–Meier method and uni- and multivariable Cox proportional hazards regression models. Results: The median PFS was 9.7 and the median OS 27.4 months. Patients treated at centers in Germany (n = 97), Ireland (n = 32), and The Netherlands (n = 43) showed a median PFS of 9.9, 9.2, and 9.7 months, OS of 34.0, 20.5, and 25.1 months, respectively. Patients >65 years had a significantly shorter PFS (9.5 vs. 9.8 months) but not OS (27.4 vs. 27.5 months) than younger patients. High tumor grade (G3/4) was associated with a shorter PFS, T4 classification with both shorter PFS and OS. Fluoropyrimidine (FP) chemotherapy backbones (doublets and single) had comparable outcomes, while patients not receiving FP backbones had a shorter PFS. In multivariable analysis, age and non-FP backbone were associated with inferior PFS, T4 classification and therapy line >2nd were significantly associated with poor PFS and OS. Conclusion: The observed survival rates confirm previous studies and demonstrate reproducible benefits of combination bevacizumab regimens. Classification T4, non-FP chemotherapy backbone, and age >65 were associated with inferior outcome

Do maize crop models catch the impact of future [CO2] on maize yield and water use?

Do maize crop models catch the impact of future [CO2] on maize yield and water use?. iCROPM2016 International Crop Modelling Symposiu

The chaos in calibrating crop models

Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.HighlightsWe propose a new approach to deriving calibration recommendations for system modelsApproach is based on analyzing calibration in multi-model simulation exercisesResulting recommendations are holistic and anchored in actual practiceWe apply the approach to calibration of crop models used to simulate phenologyRecommendations concern: objective function, parameters to estimate, software usedCompeting Interest StatementThe authors have declared no competing interest

Contractile cell forces exerted on rigid substrates

Adhesive cells including fibroblasts produce contractile forces to the underlying substrate for their locomotion. Such forces are not only high enough to deform compliant membranes such as silicone but also bend rigid micro-cantilevers. The cell-induced bending of silicon micro-cantilevers was determined using laser deflection during trypsin treatment. The observed cantilever relaxation corresponds to a contractile cell force of (16±7) µN per rat-2 fibroblast. The cantilever bending approach represents a unique method for the determination of contractile cell forces on any kind of rigid substrate in desired (physiological) environment. Hence, the fundamental technique allows building cell-based biosensors or should provide a quantitative parameter for characterising the cyto-compatibility of load bearing implant surfaces

Cardiac implant registries 2006–2016: a systematic review and summary of global experiences

Objectives: The importance of Cardiac Implant Registry (CIR) for ensuring a long-term follow-up in postmarket surveillance has been recognised and approved, but there is lack of consensus standards on how to establish a CIR. The aim of this study is to investigate the structure and key elements of CIRs in the past decade (2006–2016) and to provide recommendations on ‘best practice’ approaches. Settings and participants: A systematic search on CIR was employed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were searched: the PubMed (Medline), ScienceDirect and the Scopus database, EMBASE. After identifying the existing CIRs, an aggregative approach will be used to explore key elements emerging in the identified registries. Results: The following 82 registries were identified: 18 implantable cardioverterdefibrillator (ICD) registries, 7 cardiac resynchronisation therapy (CRT) registries, 5 pacemaker registries and 6 cardiovascular implantable electronic device registries which combined ICD, pacemaker and CRT implantation data; as well as 22 coronary stent registries and 24 transcatheteraortic heart valve implantation registries. While 71 national or local registries are from a single country, 44 are from European countries and 9 are located in USA. The following criteria have been summarised from the identified registries, including: registry working group, ethic issues, transparency, research objective, inclusion criteria, compulsory participation, endpoint, sample size, data collection basement, data collection methods, data entry, data validation and statistical analysis. Conclusions: Registries provide a ‘real-world’ picture for patients, physicians, manufacturers, payers, decision-makers and other stakeholders. CIRs are important for regulatory decisions concerning the safety and therefore approval issues of the medical device; for payers CIRs provide evidence on the medical device benefit and drive the decision whether the product should be reimbursed or not; for hospitals CIRs’ data are important for sound procurement decisions, and CIRs also help patients and their physicians to joint decision-making which of the products is the most appropriate