-
Martinez Gustafson posted an update 4 hours, 38 minutes ago
We identified inhibitors of viral mRNA biogenesis and nuclear export that exhibited no significant activity towards bulk cellular mRNA at non-cytotoxic concentrations. Among the hits is a small molecule that preferentially inhibits nuclear export of a subset of viral and cellular mRNAs without altering bulk cellular mRNA export. These findings underscore specific nuclear export requirements for viral mRNAs and phenocopy down-regulation of the mRNA export factor UAP56. This RNA export inhibitor impaired replication of diverse influenza A virus strains at non-toxic concentrations. Thus, this screening strategy yielded compounds that alone or in combination may serve as leads to new ways of treating influenza virus infection and are novel tools for studying viral RNA trafficking in the nucleus.[This corrects the article DOI 10.1371/journal.pone.0226377.].[This corrects the article DOI 10.1371/journal.pone.0227828.].Distracted driving is a leading cause of traffic accidents. It is influenced by driver attitude toward secondary tasks; however, field-based studies on the effects of low-perceived-risk tasks on lateral driving have rarely been reported. A total of 17 experienced non-professional drivers were recruited to participate in two secondary tasks a cognitive experiment (conversation) and a visual distraction experiment (observation of following vehicles), each representing low-perceived-risk secondary tasks. One-way analysis of variance (ANOVA) was conducted to evaluate the effects of low-perceived-risk tasks on lateral driving performance. ANOVA results indicated that compared with baseline (no task) lateral performance, lane-keeping ability was enhanced during cognitive distractions. In the visual distraction experiment, more than 50% of the distractions required 1-2 s. Lane deviation and its growth rate increased with the duration of distraction. Compared with cognitive distraction, lane deviation increased significantly with visual distraction, and lane-keeping performance was seriously impaired. For low-perceived-risk tasks, visual distractions impaired driving safety more seriously, compared with cognitive distractions, suggesting that drivers misjudge the risks associated with visual tasks. These results can contribute to the design of advanced driving-assistance systems and improve professional driver programs, potentially reducing the frequency of traffic accidents caused by distracted driving.Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific induction of T-cell immunity, but also with the long-term epigenetic and metabolic reprogramming of the cells from the innate immune system through a process termed trained immunity. Here we show that MTBVAC, a live attenuated strain of Mycobacterium tuberculosis, safe and immunogenic against tuberculosis antigens in adults and newborns, is also able to generate trained immunity through the induction of glycolysis and glutaminolysis and the accumulation of histone methylation marks at the promoters of proinflammatory genes, facilitating an enhanced response after secondary challenge with non-related bacterial stimuli. Importantly, these findings in human primary myeloid cells are complemented by a strong MTBVAC-induced heterologous protection against a lethal challenge with Streptococcus pneumoniae in an experimental murine model of pneumonia.[This corrects the article DOI 10.1371/journal.pone.0215999.].Enterococci are robust gram-positive bacteria that are found in a variety of surroundings and that cause a significant number of healthcare-associated infections. The genus possesses a high-efficiency pheromone-responsive plasmid (PRP) transfer system for genetic exchange that allows antimicrobial-resistance determinants to spread within bacterial populations. The pCF10 plasmid system is the best characterised, and although other PRP systems are structurally similar, they lack exact functional homologues of pCF10-encoded genes. In this review, we provide an overview of the enterococcal PRP systems, incorporating functional details for the less-well-defined systems. We catalogue the virulence-associated elements of the PRPs that have been identified to date, and we argue that this reinforces the requirement for elucidation of the less studied systems.PURPOSE To determine whether teleophthalmology can help physicians in assessing and managing eye conditions and to ascertain which clinical conditions can be addressed by teleophthalmology in primary care setting. METHODS We evaluated the resolution capacity of TeleOftalmo, strategy implemented in the public health system of southern Brazil. Resolution capacity was defined as the ability to fully address patients’ eye complaints in primary care with remote assistance from ophthalmologists. KRIBB11 cell line Data from tele-eye reports were collected over 14 months. Resolution capacity was compared across different age groups and different ocular conditions. RESULTS Overall, 8,142 patients had a tele-eye report issued in the study period. Resolution capacity was achieved in 5,748 (70.6%) patients. When stratified into age groups, the lowest capacity was 43.1% among subjects aged ≥65 years, while the highest was 89.7% among subjects aged 13-17 years (p less then 0.001). Refractive error (70.3%) and presbyopia (56.3%) were the most prevalent conditions followed by cataract (12.4%) and suspected glaucoma (7.6%). Resolution capacity was higher in cases of refractive error, presbyopia, spasm of accommodation and lid disorders than in patients diagnosed with other condition (p less then 0.001). CONCLUSIONS With telemedicine support, primary care physicians solved over two-thirds of patients’ eye or vision complaints. Refractive errors had high case resolution rates, thus having a great impact on reducing the number of referrals to specialty care. Teleophthalmology adoption in primary-care settings as part of the workup of patients with eye or vision complaints promotes a more effective use of specialty centers and will hopefully reduce waiting times for specialty referral.