Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

The effect of the apolipoprotein E genotype on response to personalized dietary advice intervention: findings from the Food4Me randomized controlled trial

Background: The apolipoprotein E (APOE) risk allele (ɛ4) is associated with higher total cholesterol (TC), amplified response to saturated fatty acid (SFA) reduction, and increased cardiovascular disease. Although knowledge of gene risk may enhance dietary change, it is unclear whether ɛ4 carriers would benefit from gene-based personalized nutrition (PN). Objectives: The aims of this study were to 1) investigate interactions between APOE genotype and habitual dietary fat intake and modulations of fat intake on metabolic outcomes; 2) determine whether gene-based PN results in greater dietary change than do standard dietary advice (level 0) and nongene-based PN (levels 1–2); and 3) assess the impact of knowledge of APOE risk (risk: E4+, nonrisk: E4−) on dietary change after gene-based PN (level 3). Design: Individuals (n = 1466) recruited into the Food4Me pan-European PN dietary intervention study were randomly assigned to 4 treatment arms and genotyped for APOE (rs429358 and rs7412). Diet and dried blood spot TC and ω-3 (n–3) index were determined at baseline and after a 6-mo intervention. Data were analyzed with the use of adjusted general linear models. Results: Significantly higher TC concentrations were observed in E4+ participants than in E4− (P < 0.05). Although there were no significant differences in APOE response to gene-based PN (E4+ compared with E4−), both groups had a greater reduction in SFA (percentage of total energy) intake than at level 0 (mean ± SD: E4+, −0.72% ± 0.35% compared with −1.95% ± 0.45%, P = 0.035; E4−, −0.31% ± 0.20% compared with −1.68% ± 0.35%, P = 0.029). Gene-based PN was associated with a smaller reduction in SFA intake than in nongene-based PN (level 2) for E4− participants (−1.68% ± 0.35% compared with −2.56% ± 0.27%, P = 0.025). Conclusions: The APOE ɛ4 allele was associated with higher TC. Although gene-based PN targeted to APOE was more effective in reducing SFA intake than standard dietary advice, there was no difference between APOE “risk” and “nonrisk” groups. Furthermore, disclosure of APOE nonrisk may have weakened dietary response to PN

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data

Empirical modelling of translation and interpreting

Empirical research is carried out in a cyclic way: approaching a research area bottom-up, data lead to interpretations and ideally to the abstraction of laws, on the basis of which a theory can be derived. Deductive research is based on a theory, on the basis of which hypotheses can be formulated and tested against the background of empirical data. Looking at the state-of-the-art in translation studies, either theories as well as models are designed or empirical data are collected and interpreted. However, the final step is still lacking: so far, empirical data has not lead to the formulation of theories or models, whereas existing theories and models have not yet been comprehensively tested with empirical methods. This publication addresses these issues from several perspectives: multi-method product- as well as process-based research may gain insights into translation as well as interpreting phenomena. These phenomena may include cognitive and organizational processes, procedures and strategies, competence and performance, translation properties and universals, etc. Empirical findings about the deeper structures of translation and interpreting will reduce the gap between translation and interpreting practice and model and theory building. Furthermore, the availability of more large-scale empirical testing triggers the development of models and theories concerning translation and interpreting phenomena and behavior based on quantifiable, replicable and transparent data