Mapping structural distribution and gating-property impacts of disease-associated mutations in voltage-gated sodium channels.

Thousands of voltage-gated sodium (Nav) channel variants contribute to a variety of disorders, including epilepsy, cardiac arrhythmia, and pain disorders. Yet, the effects of more variants remain unclear. The conventional gain-of-function (GoF) or loss-of-function (LoF) classifications are frequently employed to interpret mutations' effects and guide therapy for sodium channelopathies. Our study challenges this binary classification by analyzing 525 mutations associated with 34 diseases across 366 electrophysiology studies, revealing that diseases with similar GoF/LoF effects can stem from unique molecular mechanisms. Utilizing UniProt data, we mapped over 2,400 disease-associated missense mutations across Nav channels. This analysis pinpoints key mutation hotspots and maps patterns of gating-property impacts for the mutations, respectively, located around the selectivity filter, activation gate, fast inactivation region, and voltage-sensing domains. This study shows great potential to enhance prediction accuracy for mutational effects based on the structural context, paving the way for targeted drug design in precision medicine.

Value-based eating habits; exploring religio-cultural nutritional behavior norms.

PURPOSE: Defining a standard norm is critical in nutritional cognitive-behavioral interventions. These norms can be derived from a statistical or value-based point of view. Religion and subsequent cultural values can have significant effects on social behaviors, especially on eating habits. In this study, the authors quantify the presence of religio-cultural nutritional behavior norms in Abrahamic scriptures. METHODS: Qualitative content analysis and descriptive analysis were applied to these texts to provide a better understanding of the subject. RESULTS: The extracted norms were categorized into nine main behavioral domains, and most of the observed value-based norms were in agreement with previous experimental researches. CONCLUSION: There is strong emphasis on nutritional habits in value-based religio-cultural sources. The use of these norms in later policies and practices is advised. This approach can lead to healthier nutritional choices and a decrease in non-communicable diseases.