An Exploration of Overparenting and College Student Ability to Manage the Stress Associated with College Life

There has been an increase in the level of anxiety, perceived stress, and mental health problems among college students. An examination of the contributions of parenting to these increases may help in improving college student mental health; however, research is limited in this area. This study examined the associations between overparenting, and other types of parenting including, authoritarian, authoritative, and permissive parenting, and differentiation of self, cognitive emotion regulation, perceived stress, and state and trait anxiety. The participants were 163 undergraduate college students (74.8% identified as cisgender women, 25.2% identified as cisgender men). The participants completed questionnaires that described their mother’s and father’s parenting behavior. The participants also completed questionnaires assessing their differentiation of self, cognitive emotion regulation strategy use, perceived stress, and state and trait anxiety. The results concerning parenting and differentiation of self indicated high levels of overparenting, and authoritarian parenting by mothers and by fathers were associated with lower levels of differentiation of self. Also, high levels of authoritative and permissive parenting by mothers and by fathers were associated with higher levels of differentiation of self. The results concerning parenting and cognitive emotion regulation indicated high levels of overparenting and authoritarian parenting by mothers and by fathers were associated with higher levels of using maladaptive emotion regulation strategies. A contrasting pattern emerged with high levels of authoritative parenting and permissive parenting being associated with higher levels of using adaptive emotion regulation strategies. The results concerning parenting, perceived stress, and anxiety indicated overparenting by mothers and by fathers was related to perceived stress and trait anxiety, and overparenting by mothers was positively related to state anxiety. Authoritarian parenting by mothers and by fathers was positively related to perceived stress, while authoritative parenting by mothers was negatively associated with perceived stress, state anxiety, and trait anxiety. These findings have important clinical and developmental implications for how overparenting and other types of parenting may contribute to increased perceived stress and anxiety in college students

New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation

International audienceC407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4-NBD1 interface

New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation

AbstractC407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4–NBD1 interface.</jats:p

Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice

International audienceMutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th aminoacid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway's epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftr tm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl −) conductance in F508del Cftr tm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis

Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice

AbstractMutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th amino-acid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway’s epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftrtm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl−) conductance in F508del Cftrtm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis.</jats:p