Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disease in which patients may differ in terms of clinical course and response to drug treatment. Genetic variability may contribute to these differences by influencing drug response and clinical outcomes. This systematic review aimed to summarize the available evidence on the association between genetic variants and clinical outcomes or treatment response in patients with COPD receiving LABA- and/or LAMA-based therapies, as well as pharmacogenetic response to combination inhalants. Methods: A systematic search was conducted in the PubMed and Scopus databases, as well as in the gray literature, for studies published between 2015 and 2026. Studies were considered eligible if they included adults with COPD receiving LABA and/or LAMA treatment, including combination regimens, and evaluated genetic variants in relation to therapeutic response. Additionally, studies focusing on disease phenotypes rather than specific pharmacogenetic markers were also included. Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Cochrane Risk of Bias 2 (RoB 2) tool. Results: A total of 51 records were identified, and eight studies were included. Genetic variants in the ADRB2, FAM13A, SUMF1, MAPK8, AZU1, CSE1L , and CCL2 genes were investigated in relation to lung function, disease severity, and treatment response. ADRB2 variants (rs1042713, rs1042714, and rs1800888) were associated with lung function and exacerbation risk, although results regarding bronchodilator treatment response were inconsistent. Regarding other genetic variants, SUMF1 rs793391 emerged as a candidate variant in patients treated with combined bronchodilators and inhaled corticosteroids (ICS). However, these findings are based on limited data and currently lack independent replication, warranting cautious interpretation. Furthermore, findings from large GWAS revealed novel candidates associated with treatment outcomes, though these results were not replicated in subsequent independent enome-Wide Association Study analyses. Due to the limited number of studies and considerable heterogeneity, no meta-analysis was performed. Conclusion: This review highlights the latest advances in COPD pharmacogenetics by synthesizing available evidence on patient responses to bronchodilators and corticosteroids. By mapping key methodological factors, the review provides valuable insight into optimizing future research. Systematic Review Registration: www.crd.york.ac.uk/prospero/ , identifier CRD420261392469.

Staphylococcus aureus causes diverse clinical manifestations, from asymptomatic colonization to severe invasive disease. Host genetic factors influencing infection susceptibility and severity remain incompletely understood. This systematic review, conducted according to PRISMA 2020 guidelines and registered in PROSPERO, evaluated human genetic variants associated with susceptibility to S.aureus infection and colonization, with subsequent clinical outcomes. Bibliographic databases and grey literature sources were searched for observational studies (2015-2026), with risk of bias assessed using the Newcastle-Ottawa Scale. Regarding innate immunity, IL1RN*2/*2 was associated with post-traumatic S. aureus osteomyelitis, whereas the TIRAP association lost significance after adjustment. In adaptive immunity, admixture mapping linked European ancestry at HLA class II locus to bacteremia in African Americans, while CCR5Δ32 altered circulating chemokines levels without altering clinical risk. Regarding metabolism and iron regulation, GLS2 variant (rs937115) was associated with complicated bacteremia, and an intergenic CHCHD7/SDR16C5 variant (rs73596248) was linked to higher hepcidin levels and a lower risk of bacteremia. CFTR F508del genotype showed no significant association with methicillin-resistant S. aureus (MRSA) acquisition. These findings support a multifactorial host genetic network in S. aureus infection and underscore the need for larger, multi-ancestry, independently replicated studies to validate genetic markers for future risk stratification.