A Transgenic Drosophila Model Demonstrates That the Helicobacter pylori CagA Protein Functions as a Eukaryotic Gab Adaptor

Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA) protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK) pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab) adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS). Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW). These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function

A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition

IntroductionThere is an emerging need for plant-based, vegan options for patients requiring nutritional support.MethodsTwenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed.ResultsPatients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition (‘MUST’ score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p > 0.06) with no serious adverse events related.DiscussionThis study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition

Between secularization and religious reorganization – the religiosity of Polish and Turkish new immigrants in Germany

Dieser Beitrag befasst sich mit der Bedeutung von Religion im Prozess der Integration von Einwanderern in Deutschland. Gestützt auf neueste Daten (SCIP 2010/11) einer Befragung unter polnischen und türkischen Neuzuwanderern wird untersucht, welchen Einfluss das Migrationsereignis als solches auf Religiosität ausübt und wie sich religiöse Partizipation und private religiöse Praxis in der Frühphase der Integration verändern. Die Untersuchung bestätigt, erstens, dass beide Gruppen einen markanten Rückgang religiöser Partizipation erfahren. Dass dieser Rückgang bei muslimischen Türken stärker ausfällt als bei katholischen Polen und sich insbesondere beim Kirchgang oder Moscheebesuch, weniger dagegen bei der privaten Gebetspraxis nachweisen lässt, deutet auf die Bedeutung religiöser Opportunitätsstrukturen hin. Zweitens zeigt sich, dass bei den polnischen Neuzuwanderern der Rückgang an Religiosität mit starken Bindungen in die säkulare deutsche Aufnahmegesellschaft verknüpft ist, während dies bei den türkischen Neuankömmlingen nicht der Fall ist. Nur für jene lässt sich, drittens, beobachten, dass dem anfänglichen Einbruch der Religiosität mit dem Aufenthalt in Deutschland ein allmählicher Wiederanstieg folgt. Die Befunde deuten darauf, dass assimilationstheoretische Argumente um Überlegungen zu Dynamiken symbolischer Grenzziehung zu erweitern sind, die gruppenspezifische Muster des Wandels von Religiosität zu erfassen gestatten. Aufgrund solcher komplexer Dynamiken religiösen Wandels im Migrationsgeschehen ist insgesamt damit zu rechnen, dass öffentlich sichtbare religiöse Diversität ein dauerhaftes Merkmal moderner Einwanderungsgesellschaften darstellen wird.publishe

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc