A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets

Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences. © 2018 The Author(s)

Mapping potential amplification and transmission hotspots for MERS-CoV, Kenya

Dromedary camels have been implicated consistently as the source of Middle East respiratory syndrome coronavirus (MERS-CoV) human infections and attention to prevent and control it has focused on camels. To understanding the epidemiological role of camels in the transmission of MERS-CoV, we utilized an iterative empirical process in Geographic Information System (GIS) to identify and qualify potential hotspots for maintenance and circulation of MERS-CoV, and produced risk-based surveillance sites in Kenya. Data on camel population and distribution were used to develop camel density map, while camel farming system was defined using multi-factorial criteria including the agro-ecological zones (AEZs), production and marketing practices. Primary and secondary MERS-CoV seroprevalence data from specific sites were analyzed, and location-based prevalence matching with camel densities was conducted. High-risk convergence points (migration zones, trade routes, camel markets, slaughter slabs) were profiled and frequent cross-border camel movement mapped. Results showed that high camel-dense areas and interaction (markets and migration zones) were potential hotspot for transmission and spread. Cross-border contacts occurred with in-migrated herds at hotspot locations. AEZ differential did not influence risk distribution and plausible risk factors for spatial MERS-CoV hotspots were camel densities, previous cases of MERS-CoV, high seroprevalence and points of camel convergences. Although Kenyan camels are predisposed to MERS-CoV, no shedding is documented to date. These potential hotspots, determined using anthropogenic, system and trade characterizations should guide selection of sampling/surveillance sites, high-risk locations, critical areas for interventions and policy development in Kenya, as well as instigate further virological examination of camels.The United States Agency for International Development through the MERS-CoV applied research activities in Middle East and North East Africa under the USAID’s Emerging Pandemic Threats Program (OSRO/GLO/505/USA).http://link.springer.com/journal/103932019-06-01hj2018Veterinary Tropical Disease

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.Peer reviewe

Determinants of Substance Abuse among Incarcerated Adolescents: Implications for Brief Treatment and Crisis Intervention

This study assessed the determinants of substance abuse among incarcerated youth. Because substance abuse is a predictor of incarceration and conduct disorder is known to increase the chances of youth abusing substances, the purpose of this study was to determine what seminal symptoms of conduct disorder seem to be the risk factors for substance abusers among incarcerated youth. Data were collected on 83 youth in southern Oregon, 74 males and 9 females. Logistic regression found the overall model containing 6 symptoms of conduct disorder to be significantly related to substance abuse (p , .001). When looking at the 6 symptoms individually, however, only running away from home was significantly related to substance abuse (p , .001). Incarcerated youth who reported running away from home were more than 9 times likely to abuse substances than incarcerated youth who did not report running away from home. This indicates the importance of conducting brief therapy for the prevention and intervention of youth running away from home. The article concludes with a discussion on the importance of assessments, treatment plans, and conducting the harm-reduction approach. [Brief Treatment and Crisis Intervention 7:34-39 (2007)

Childhood Bullying Victimization, Substance Use and Criminal Activity among Adolescents: A Multilevel Growth Model Study

Background: This study aims to examine the effects of childhood bullying victimization (CBV) on substance use and criminal activity among adolescents over time. In addition, it identifies the moderating effects of gender and race/ethnicity on the associations of CBV with substance abuse and criminal activity in adolescence and young adulthood. Methods: This study included 8984 adolescents aged 12 to 18 years (Mage = 14.22 years) assessed biennially at four time points utilizing the National Longitudinal Survey of Youth 1997. The two-level hierarchical linear modeling was employed to test the effects of CBV on substance use and criminal activity. Results: The incidence of substance use increased over time throughout adolescence to young adulthood, while that of criminal activity decreased. CBV increased the risks of cigarette use, marijuana use, and criminal activity. Gender and race/ethnicity significantly moderated the effect of CBV on alcohol use and alcohol binges. The effect of CBV on alcohol use was stronger among females than males. Among Hispanic adolescents, CBV was more strongly related to alcohol use and binges compared to non-Hispanic White. Conclusion: Findings suggest the need for early intervention for children at high risk of being bullied to reduce later substance abuse and involvement in criminal activities. Considering the moderating effects of gender and ethnicity on the associations, target-specified intervention and prevention programs are also required. Further studies focusing on the lifelong effects of CBV beyond adolescence are recommended