Academic Burnout In College Students: The Impact of Personality Characteristics and Academic Term on Burnout

Burnout is a condition which can affect people in a variety of settings. It is associated with reduced productivity and satisfaction; increased rates of mood disorders such as depression and anxiety and a plethora of physical problems including increased inflammation biomarkers and cardiovascular disease, metabolic syndrome, sleep disturbances, changes in appetite, fatigue, lowered immunity, headaches, and gastrointestinal distress. Burnout has primarily been studied as an occupational hazard, but there is increasing evidence that it is a condition that can be experienced in other settings, such as school. The purpose of this study was to investigate how personality characteristics (such as extraversion, conscientiousness, neuroticism) and term classification (freshman, sophomore, etc.) affect academic burnout in a sample of college students. This paper includes a brief summary of the history of the study of burnout, a discussion of the existing literature on the topic, hypotheses suggested by previous studies conducted in this field, and a description of the method, results, limitations, possible future directions and conclusions of this study

CFTR and Ca2+ Signaling in Cystic Fibrosis

Among the diverse physiological functions exerted by calcium signaling in living cells, its role in the regulation of protein biogenesis and trafficking remains incompletely understood. In cystic fibrosis (CF) disease the most common CF transmembrane conductance regulator (CFTR) mutation, F508del-CFTR generates a misprocessed protein that is abnormally retained in the endoplasmic reticulum (ER) compartment, rapidly degraded by the ubiquitin/proteasome pathway and hence absent at the plasma membrane of CF epithelial cells. Recent studies have demonstrated that intracellular calcium signals consequent to activation of apical G-protein-coupled receptors by different agonists are increased in CF airway epithelia. Moreover, the regulation of various intracellular calcium storage compartments, such as ER is also abnormal in CF cells. Although the molecular mechanism at the origin of this increase remains puzzling in epithelial cells, the F508del-CFTR mutation is proposed to be the onset of abnormal Ca2+ influx linking the calcium signaling to CFTR pathobiology. This article reviews the relationships between CFTR and calcium signaling in the context of the genetic disease CF

Abnormal spatial diffusion of Ca2+ in F508del-CFTR airway epithelial cells

<p>Abstract</p> <p>Background</p> <p>In airway epithelial cells, calcium mobilization can be elicited by selective autocrine and/or paracrine activation of apical or basolateral membrane heterotrimeric G protein-coupled receptors linked to phospholipase C (PLC) stimulation, which generates inositol 1,4,5-trisphosphate (IP₃) and 1,2-diacylglycerol (DAG) and induces Ca²⁺release from endoplasmic reticulum (ER) stores.</p> <p>Methods</p> <p>In the present study, we monitored the cytosolic Ca²⁺transients using the UV light photolysis technique to uncage caged Ca²⁺or caged IP₃into the cytosol of loaded airway epithelial cells of cystic fibrosis (CF) and non-CF origin. We compared in these cells the types of Ca²⁺receptors present in the ER, and measured their Ca²⁺dependent activity before and after correction of F508del-CFTR abnormal trafficking either by low temperature or by the pharmacological corrector miglustat (N-butyldeoxynojirimycin).</p> <p>Results</p> <p>We showed reduction of the inositol 1,4,5-trisphosphate receptors (IP₃R) dependent-Ca²⁺response following both correcting treatments compared to uncorrected cells in such a way that Ca²⁺responses (CF+treatment <it>vs </it>wild-type cells) were normalized. This normalization of the Ca²⁺rate does not affect the activity of Ca²⁺-dependent chloride channel in miglustat-treated CF cells. Using two inhibitors of IP₃R1, we observed a decrease of the implication of IP₃R1 in the Ca²⁺response in CF corrected cells. We observed a similar Ca²⁺mobilization between CF-KM4 cells and CFTR-cDNA transfected CF cells (CF-KM4-reverted). When we restored the F508del-CFTR trafficking in CFTR-reverted cells, the specific IP₃R activity was also reduced to a similar level as in non CF cells. At the structural level, the ER morphology of CF cells was highly condensed around the nucleus while in non CF cells or corrected CF cells the ER was extended at the totality of cell.</p> <p>Conclusion</p> <p>These results suggest reversal of the IP₃R dysfunction in F508del-CFTR epithelial cells by correction of the abnormal trafficking of F508del-CFTR in cystic fibrosis cells. Moreover, using CFTR cDNA-transfected CF cells, we demonstrated that abnormal increase of IP₃R Ca²⁺release in CF human epithelial cells could be the consequence of F508del-CFTR retention in ER compartment.</p

Mechanisms of the noxious inflammatory cycle in cystic fibrosis

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis

Mécanismes et correction pharmacologique de l'adressage de la protéine mutée F508del-CFTR

La délétion sur le gène CFTR (Cystic Fibrosis Transmembrane conductance Regulator) d une phénylalanine en position 508 est à l origine d une activation et d un adressage défectueux de la protéine traduite. L objectif de ce travail a été de découvrir des molécules corrigeant l adressage du F508del-CFTR. Le miglustat, en inhibant la déglucosylation du F508del-CFTR prévient son interaction avec la calnexine et permet son adressage à la membrane plasmique. De même, la modulation du taux de calcium réticulaire, en prévenant l interaction F508del-CFTR/calnexine, permet la correction du F508del-CFTR. Enfin, nous avons démontré que les sels de benzo[c]quinolizinium, en se fixant sur la glycine 622 du F508del-CFTR inhibent sa dégradation et permettent son adressage. La recherche des mécanismes impliqués dans cette correction pharmacologique a ainsi permis de révéler de nouvelles cibles potentielles dans la mise en place d un traitement de la mucoviscidose.Most patients suffering from Cystic Fibrosis have the F508del mutation on at least one CFTR (Cystic Fibrosis Transmembrane conductance Regulator) allele which results in misfolding and gating flaw of CFTR. The aim of this work was focused on identifying compounds able to rescue the trafficking of F508del-CFTR. By inhibiting the deglucosylation of F508del-CFTR, miglustat, an a,1-2 glucosidase inhibitor, rescues the F508del-CFTR protein to the cell surface preventing its interaction with calnexin. Moreover, the modulation of Ca2+ level in the endoplasmic reticulum corrects F508del-CFTR trafficking preventing its interaction with calnexin. Finally, we identified a novel mechanism for correction of F508del-CFTR by the benzo[c]quinolizinium potentiators interacting with CFTR via the amino acid G622 to protect the channel from proteasome degradation. Research on the mechanisms of biosynthesis, trafficking and degradation of F508del-CFTR protein reveals new strategies for CF drug targets.POITIERS-BU Sciences (861942102) / SudocSudocFranceF

Implication des protéines chaperonnes dans la rétention réticulaire de la protéine F508del-CFTR

La mucoviscidose est une maladie génétique ayant pour origine des mutations de la protéine CFTR (cystic fibrosis transmembrane conductance regulator). La plus fréquente de ces mutations correspond à la délétion d'une phénylalanine en position 508 (F508del) et se traduit par un défaut d'adressage de la protéine mutée qui est alors retenue par le système de contrôle qualité du réticulum endoplasmique (ERCQ) et plus particulièrement par le cycle de la calnexine. Ce cycle compte plusieurs acteurs principaux, des protéines chaperonnes, des co-chaperonnes et des enzymes. L'objectif de cette étude est donc de démontrer l'implication et le rôle de ces partenaires avec la protéine naissante dans la rétention de la protéine F508del-CFTR. Pour cela, une stratégie de siRNA de ces protéines a été mise en place. Dans une première étude, nous avons pu mettre en évidence l'implication de protéines impliquées dans l'entrée du cycle de la calnexine. Et dans une deuxième étude, nous avons démontré l'importance de protéines impliquées dans la sortie du cycle de la calnexine. Nos travaux démontrent donc l'implication du cycle de la calnexine dans la rétention de la protéine F508del-CFTR ainsi que l'importance de l'interaction entre la calnexine et la protéine F508del-CFTR. De façon intéressante, ces études ont permis d'identifier d'éventuelles nouvelles cibles thérapeutiques pour le traitement de la mucoviscidose.Cystic fibrosis is a genetic disorder characterized by mutations on the CFTR (cystic fibrosis transmembrane conductance regulator). The most common mutation is a deletion of a phenylalanine at position 508, F508del, results in trafficking default of CFTR protein that is retained in the endoplasmic reticulum quality control (ERQC) and especially by the calnexin cycle. This cycle has several main proteins, the chaperones, co-chaperones and enzymes. The aim of this work is to demonstrate the involvement and role of these partners with the nascent protein in the retention of F508del-CFTR protein. For this, an siRNA strategy of these proteins was established. In a first study, we demonstrated the implication of proteins involved in the entrance of calnexin cycle. And in a second study, we demonstrated the importance of proteins involved in the release calnexin cycle. Our studies highlight the implication of calnexine cycle in the F508del-CFTR protein. Interestingly, these studies have identified potential new therapeutic targets for the treatment of cystic fibrosis.POITIERS-BU Sciences (861942102) / SudocSudocFranceF