Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are major drivers of multidrug resistance among gram-negative bacteria. Cations, such as Mg, become concentrated within the periplasm and, in contrast to the cytoplasm, its pH is sensitive to conditions outside the cell. Here, we reveal an interplay between Mg and pH in modulating the structural dynamics of the periplasmic adapter protein, AcrA, and its function within the prototypical AcrAB-TolC multidrug pump from Escherichia coli.
View Article and Find Full Text PDFTo date, sparse attention has been paid to the importance of the "lived experience" of participants and their caregivers in pediatric gene therapy (GT) trials for rare genetic neurological disorders. Pediatric GT studies differ meaningfully from adult GT studies as the decision to participate involves a dyad: the child participant and their caregiver(s). As a multistakeholder group of authors, we are a diverse group with expert perspectives on the social, emotional, physical, and logistical burdens/benefits of trial participation and the myriad ways they affect pediatric GT research.
View Article and Find Full Text PDFBackground: Type 2 Diabetes (T2D) is a complex condition marked by insulin resistance and beta-cell dysfunction. Traditional dietary interventions, such as low-calorie or low-carbohydrate diets, typically overlook individual variability in postprandial glycemic responses (PPGRs), which can lead to suboptimal management of the disease. Recent advancements suggest that personalized nutrition, tailored to individual metabolic profiles, may enhance the effectiveness of T2D management.
View Article and Find Full Text PDFTranscranial focused ultrasound (FUS) is a versatile, MR-guided, incisionless intervention with diagnostic and therapeutic applications for neurologic and psychiatric diseases. It is currently FDA-approved as a thermoablative treatment of essential tremor and Parkinson disease. However, other applications of FUS including BBB opening for diagnostic and therapeutic applications, sonodynamic therapy, histotripsy, and low-intensity focused ultrasound neuromodulation are all in clinical trials.
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