Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes.

miRNA(miR)-124 is an important regulator of neurogenesis, but its upregulation in SOD1G93A motor neurons (mSOD1 MNs) was shown to associate with neurodegeneration and microglia activation. We used pre-miR-124 in wild-type (WT) MNs and anti-miR-124 in mSOD1 MNs to characterize the miR-124 pathological role. miR-124 overexpression in WT MNs produced a miRNA profile like that of mSOD1 MNs (high miR-125b; low miR-146a and miR-21), and similarly led to early apoptosis. Alterations in mSOD1 MNs were abrogated with anti-miR-124 and changes in their miRNAs mostly recapitulated by their secretome. Normalization of miR-124 levels in mSOD1 MNs prevented the dysregulation of neurite network, mitochondria dynamics, axonal transport, and synaptic signaling. Same alterations were observed in WT MNs after pre-miR-124 transfection. Secretome from mSOD1 MNs triggered spinal microglia activation, which was unno-ticed with that from anti-miR-124-modulated cells. Secretome from such modulated MNs, when added to SC organotypic cultures from mSOD1 mice in the early symptomatic stage, also coun-teracted the pathology associated to GFAP decrease, PSD-95 and CX3CL1-CX3CR1 signaling im-pairment, neuro-immune homeostatic imbalance, and enhanced miR-124 expression levels. Data suggest that miR-124 is implicated in MN degeneration and paracrine-mediated pathogenicity. We propose miR-124 as a new therapeutic target and a promising ALS biomarker in patient sub-populations.

Absence of methicillin-resistant Staphylococcus aureus colonization among immunocompetent healthy adults: Insights from a longitudinal study.

Methicillin-resistant Staphylococcus aureus (MRSA) has long been known as a major cause of hospital-acquired (HA-MRSA) infections worldwide. For the past twenty years, an increasing number of studies have described its emergence in the community as well. In Portugal, a country with a high-prevalence of HA-MRSA, there are only limited data available on the epidemiology of MRSA in the community. We studied the prevalence of S. aureus and MRSA colonization among healthy adults in Portugal. Between February 2015 and December 2016, a longitudinal study was conducted in which 87 adults aged 25-50 years old were followed for six months. For each participant nasopharyngeal, oropharyngeal and saliva samples were obtained monthly and, in some cases, weekly. A total of 1,578 samples (n = 526 for each sampling site) were examined for the presence of S. aureus and MRSA by classical culture-based methods. Fifty-seven adults (65.5%) carried S. aureus at least once during the six months period of the study: 19.5% were persistent S. aureus carriers and 46.0% were intermittent carriers. Carriage rates per sampling site were 20.5% in nasopharynx, 18.3% in oropharynx, and 13.5% in saliva. Simultaneous screening of the three sampling sites increased detection of S. aureus, which overall occurred in 34.4% of the 526 sampling time-points. No MRSA were isolated. In conclusion, this study adds novel information about the MRSA scenario in the Portuguese community. Our results indicate that, in Portugal, MRSA does not seem to circulate among healthy adults without risk factors and therefore this age group does not constitute, at the current time, a reservoir of MRSA in the community.