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The current investigation uses longitudinal data to begin to understand the correlates of gender integration and youth emotional adjustment. Participants were 207 adolescents (mean age = 11.11 years, 53% female). The results demonstrated that, when compared to only having gender-segregated peer affiliates, gender-integrated peer affiliates, as well as the transition from gender-segregated to gender-integrated peer affiliations from the beginning to the end of the sixth-grade academic year was associated with significantly higher levels of self-esteem. Descriptive data also indicate that gender segregation was associated with lower levels of depressive symptoms, although the effects on depressive symptomology did not reach traditional levels of statistical significance. The findings highlight the important emotional impact of gender-diverse peer relationships among young adolescents.

Rathayibacter toxicus is Gram-positive bacterium causing gummosis of forage grasses, and it produces a corynetoxin responsible for livestock poisonings in Australia. R. toxicus is a USDA APHIS-listed Select Agent, threatening seed and livestock production areas in the U.S. We therefore are developing diagnostic assays to prepare for the introduction of the pathogen into the U.S. Using proteomic data, we identified proteins expressed in R. toxicus but not in other Rathayibacter spp. Recombinant proteins corresponding to extracellular domains of candidate proteins were used to raise polyclonal and monoclonal antibodies. Antibodies were evaluated for sensitivity and specificity in immunoassays against a panel of Rathayibacter spp. and near-neighbours. Polyclonal and monoclonal antibodies exhibited high sensitivity and specificity for R. toxicus in assays with cultured bacteria. The highest-performing immunoreagents were identified for further testing with field samples collected in Australia and for eventual development of an immunoassay for bacterial detection in grass samples.

Tunicaminyluracil antibiotics are a novel class of toxigenic glycolipids that are synthesized by several soil-associated Actinomycetes. The acquisition of a tunicaminyluracil biosynthetic gene cluster (TGC) in Rathayibacter toxicus has led to the emergence of the only described, naturally occurring tunicaminyluracil-associated mammalian disease, annual ryegrass toxicity of livestock. Endemic to Australia, R. toxicus is obligately vectored by Anguinid seed gall nematodes to the developing seedheads of forage grasses, in which the bacteria synthesize tunicaminyluracils that may subsequently be consumed by livestock and result in high rates of mortality and morbidity. The potential impact of R. toxicus on U.S. agriculture has led the U.S. Department of Agriculture – Animal and Plant Health Inspection Service to list R. toxicus as a Plant Pathogen Select Agent. R. toxicus is the only characterized phytopathogenic bacterium to produce tunicaminyluracils, but numerous R. toxicus-like livestock poisonings outside Australia suggest additional bacterial sources of tunicaminyluracils may exist. To investigate the conservation of the TGC in R. toxicus and whether the TGC is present in other Rathayibacter species, we analyzed genome sequences of members of the Rathayibacter genus. Putative TGCs were identified in genome sequences of R. toxicus, R. iranicus, R. agropyri, and an undescribed South African Rathayibacter species. In the latter three species, the putative TGCs have homologs of tunicaminyluracil-related genes essential for toxin production, but the TGCs differ in gene number and order. The TGCs appear at least partially functional because in contrast to atoxigenic species, TGC-containing Rathayibacter species were each able to tolerate exogenous applications of tunicamycin from Streptomyces chartreusis. The North American R. agropyri TGC shows extensive diversity among the sequenced isolates, with presense/absense polymorphisms in multiple genes or even the whole TGC. R. agropyri TGC structure does not appear to correlate with date or location of isolate collection. The conservation and identification of tunicaminyluracil-related gene clusters in three additional Rathayibacter species isolated from South Africa, the Middle East, and the United States, suggests a wider global distribution of potentially neurotoxigenic plant-associated bacteria. This potential for additional endemic and exotic toxigenic Rathayibacter species could have widespread and severe implications for agriculture.

Objective To assess changes in the use of essential maternal and child health services in Konobo, Liberia, after implementation of an enhanced community health worker (CHW) programme. Methods The Liberian Ministry of Health partnered with Last Mile Health, a nongovernmental organization, to implement a pilot CHW programme with enhanced recruitment, training, supervision and compensation. To assess changes in maternal and child health-care use, we conducted repeated cross-sectional cluster surveys before (2012) and after (2015) programme Implementation. Findings Between 2012 and 2015, 54 CHWs, seven peer supervisors and three clinical supervisors were trained to serve a population of 12 127 people in 44 communities. The regression-adjusted percentage of children receiving care from formal care providers increased by 60.1 (95% confidence interval, CI: 51.6 to 68.7) percentage points for diarrhoea, by 30.6 (95% CI: 20.5 to 40.7) for fever and by 51.2 (95% CI: 37.9 to 64.5) for acute respiratory infection. Facility-based delivery increased by 28.2 points (95% CI: 20.3 to 36.1). Facility-based delivery and formal sector care for acute respiratory infection and diarrhoea Increased more in agricultural than gold-mining communities. Receipt of one-or-more antenatal care sessions at a health facility and postnatal care within 24 hours of delivery did not change significantly. Conclusion We identified significant increases in uptake of child and maternal health-care services from formal providers during the pilot CHW programme in remote rural Liberia. Clinic-based services, such as postnatal care, and services in specific settings, such as mining areas, require additional interventions to achieve optimal outcomes. Objectif Evaluer les changements dans le recours aux services essentiels de sante maternelle et infantile a Konobo, au Liberia, apres la mise en oeuvre d'un programme de perfectionnement des agents de sante communautaires. Methodes Le ministere de la Sante liberien s'est associe avec Last Mile Health, une organisation non gouvernementale, afin de mettre en oeuvre un programme pilote destine a ameliorer le recrutement, la formation, l'encadrement et la remuneration des agents de sante communautaires. Pour evaluer les changements au niveau des soins de sante maternelle et infantile, nous avons realise plusieurs sondages transversaux par grappes avant (2012) et apres (2015) la mise en oeuvre du programme. Resultats Entre 2012 et 2015, 54 agents de sante communautaires, sept collegues superviseurs et trois superviseurs cliniques ont ete formes pour prendre en charge une population de 12127 personnes dans 44 communautes. Le pourcentage corrige par regression d'enfants recevant des soins de la part de prestataires de soins officiels a augmente de 60,1 (intervalle de confiance (IC) de 95%: 51,6 a 68,7) points de pourcentage pour la diarrhee, de 30,6 (IC 95%: 20,5 a 40,7) pour la fievre et de 51,2 (IC 95%: 37,9 a 64,5) pour les infections aigues des voies respiratoires. Les accouchements en maternite ont augmente de 28,2 points (IC 95%: 20,3 a 36,1). Les accouchements en maternite et la prise en charge dans le secteur formel des infections aigues des voies respiratoires et des cas de diarrhee ont davantage augmente dans les communautes agricoles que dans celles vivant de l'extraction de l'or. Nous n'avons pas observe de changements significatifs dans le fait de beneficier d'une ou plusieurs seances de soins prenataux dans une structure de soins ou de soins post-partum dans les 24 heures suivant l'accouchement. Conclusion Nous avons observe une augmentation significative de la prestation de services de sante maternelle et infantile par des prestataires officiels lors du programme pilote destine aux agents de sante communautaires dans les regions rurales isolees du Liberia. Des interventions supplementaires sont necessaires pour obtenir des resultats optimaux vis-a-vis de la prestation de services cliniques, comme les soins post-partum, et de services dans des zones specifiques, comme les regions minieres. Objetivo Evaluar los cambios en el uso de servicios de salud materna e infantil basicos en Konobo, Liberia, tras la implementacion de un programa mejorado de trabajadores comunitarios de salud (CHW, por sus siglas en ingles). Metodos El Ministerio de Salud de Liberia se asocio con Last Mile Health, una organizacion no gubernamental, para implementar un programa piloto de CHW con una mejora en la contratacion, formacion, supervision y compensacion. Para evaluar los cambios en el uso de la atencion sanitaria materna e infantil, se realizaron repetidas encuestas transversales de conglomerados antes (2012) y despues (2015) de la implementacion del programa. Resultados Entre 2012 y 2015, 54 CHW, 7 supervisores homologos y 3 supervisores clinicos recibieron formacion para trabajar para una poblacion de 12 127 personas en 44 comunidades. El porcentaje ajustado a la regresion de ninos que recibieron atencion de profesionales sanitarios formales aumento un 60,1% (intervalo de confianza (IC) del 95%: 51,6 a 68,7) para la diarrea, un 30,6% (IC del 95%: 20,5 a 40,7) para la fiebre y un 51,2% (IC del 95%: 37,9 a 64,5) para la Infeccion respiratoria aguda. El suministro en centros aumento un 28,2% (IC del 95%: 20,3 a 36,1). El suministro en centros y la atencion del sector formal para la Infeccion respiratoria aguda y la diarrea aumentaron mas en comunidades agricolas que en las de minas de oro. La recepcion de una o mas sesiones de atencion prenatal en un centro sanitario y de atencion posparto a las 24 horas del parto no experimento cambios importantes. Conclusion Se identificaron aumentos significativos en la aceptacion de los servidos de atencion sanitaria materna e infantil de profesionales formales durante la version piloto del programa de CHW en la Liberia rural remota. Los servicios clinicos, como la atencion posparto y los servicios en lugares concretos, como zonas mineras, requieren intervenciones adicionales para lograr unos resultados optimos., Introduction Over 95% of global maternal and child deaths occur in 75 low-and middle-income countries and remote populations within these countries often bear the greatest burden. (1,2) Many countries are [...]

Little is known about the skills children need to successfully collaborate with classmates on academic assignments. The purposes of this study were to identify grade-schoolers' collaborative skills, evaluate the importance of identified skills for collaborative work, and determine whether differences in skill use were related to children's social and scholastic competence. Initially, third through fifth graders ("N" = 113) described attributes of "good" collaborators, and these attributes were distilled into distinct skill categories or "types." Next, third through fifth graders ("N" = 212) rated exemplars of each skill type as a basis for skill importance and peers' skill use and provided data that were used to construct measures of work partner preference and peer acceptance. Teachers reported on participants' achievement in multiple academic domains. Four categories of work-related and interpersonal skills were identified, and these skill types were differentially associated with children's work partner preferences, peer acceptance, and achievement. Overall, the findings help to specify the types of skills grade-schoolers need to relate effectively with classmates in the context of collaborative academic tasks.

ABSTRACT Rathayibacter toxicus is a species of Gram-positive, corynetoxin-producing bacteria that causes annual ryegrass toxicity, a disease often fatal to grazing animals. A phylogenomic approach was employed to model the evolution of R. toxicus to explain the low genetic diversity observed among isolates collected during a 30-year period of sampling in three regions of Australia, gain insight into the taxonomy of Rathayibacter, and provide a framework for studying these bacteria. Analyses of a data set of more than 100 sequenced Rathayibacter genomes indicated that Rathayibacter forms nine species-level groups. R. toxicus is the most genetically distant, and evidence suggested that this species experienced a dramatic event in its evolution. Its genome is significantly reduced in size but is colinear to those of sister species. Moreover, R. toxicus has low intergroup genomic diversity and almost no intragroup genomic diversity between ecologically separated isolates. R. toxicus is the only species of the genus that encodes a clustered regularly interspaced short palindromic repeat (CRISPR) locus and that is known to host a bacteriophage parasite. The spacers, which represent a chronological history of infections, were characterized for information on past events. We propose a three-stage process that emphasizes the importance of the bacteriophage and CRISPR in the genome reduction and low genetic diversity of the R. toxicus species. IMPORTANCE Rathayibacter toxicus is a toxin-producing species found in Australia and is often fatal to grazing animals. The threat of introduction of the species into the United States led to its inclusion in the Federal Select Agent Program, which makes R. toxicus a highly regulated species. This work provides novel insights into the evolution of R. toxicus. R. toxicus is the only species in the genus to have acquired a CRISPR adaptive immune system to protect against bacteriophages. Results suggest that coexistence with the bacteriophage NCPPB3778 led to the massive shrinkage of the R. toxicus genome, species divergence, and the maintenance of low genetic diversity in extant bacterial groups. This work contributes to an understanding of the evolution and ecology of an agriculturally important species of bacteria.

A social-cognitive framework was used to generate and test hypotheses regarding the role of children's causal attributions for peer victimization in predicting how they cope with such experiences. It was hypothesized that attributions would be differentially associated with coping as a function of the direction (i.e., upward, horizontal, or downward) of the social comparison reflected in children's perceived cause for their peer victimization. Self- and peer-reports were collected on 224 (97 boys, 127 girls) fourth- and sixth-grade ethnically diverse students (M[subscript age] = 10.6 years, SD = 1.08 years). Only children who had been targeted for peer aggression within the preceding two months were included to ensure they had a basis for answering questions regarding the cause of their victimization and how they coped. Data were gathered in the fall and spring of the academic school year and included reports of causal attributions, victimization, aggression, peer acceptance, and coping with victimization. Multiple regression analyses provided preliminary evidence that children's attributions were differentially predictive of changes in coping responses. For example, attributing victimization to one's race predicted decreases in seeking friend support and increases in nonchalance, whereas attributing it to not being as "cool" as others was associated with increases in seeking teacher and friend support, but decreases in nonchalance. Results suggest that children's attributions may reflect the resources they have available to them to cope with victimization. Such resources may be due to social status, or they may be due to the extent to which children blame themselves for the victimization (e.g., the degree to which they expect sympathy and help). Implications of these differential patterns of attributions and coping strategies for children's adjustment are discussed. (Contains 4 tables and 1 figure.)

Rathayibacter toxicus is a forage grass associated Gram-positive bacterium of major concern to food safety and agriculture. This species is listed by USDA-APHIS as a plant pathogen select agent because it produces a tunicamycin-like toxin that is lethal to livestock and may be vectored by nematode species native to the U.S. The complete genomes of two strains of R. toxicus, including the type strain FH-79, were sequenced and analyzed in comparison with all available, complete R. toxicus genomes. Genome sizes ranged from 2,343,780 to 2,394,755 nucleotides, with 2079 to 2137 predicted open reading frames; all four strains showed remarkable synteny over nearly the entire genome, with only a small transposed region. A cluster of genes with similarity to the tunicamycin biosynthetic cluster from Streptomyces chartreusis was identified. The tunicamycin gene cluster (TGC) in R. toxicus contained 14 genes in two transcriptional units, with all of the functional elements for tunicamycin biosynthesis present. The TGC had a significantly lower GC content (52%) than the rest of the genome (61.5%), suggesting that the TGC may have originated from a horizontal transfer event. Further analysis indicated numerous remnants of other potential horizontal transfer events are present in the genome. In addition to the TGC, genes potentially associated with carotenoid and exopolysaccharide production, bacteriocins and secondary metabolites were identified. A CRISPR array is evident. There were relatively few plant-associated cell-wall hydrolyzing enzymes, but there were numerous secreted serine proteases that share sequence homology to the pathogenicity-associated protein Pat-1 of Clavibacter michiganensis. Overall, the genome provides clear insight into the possible mechanisms for toxin production in R. toxicus, providing a basis for future genetic approaches.

Summary In non-small cell lung cancer cell lines, activation of β-catenin independent signaling, via Wnt7a/Frizzled9 signaling, leads to reversal of cellular transformation, reduced anchorage-independent growth and induction of epithelial differentiation. miRNA expression profiling on a human lung adenocarcinoma cell line (A549) identified hsa-miR29b as an important downstream target of Wnt7a/Frizzled9 signaling. We show herein that hsa-miR29b expression is lost in non-small cell lung cancer (NSCLC) cell lines and stimulation of β-catenin independent signaling, via Wnt7a expression, in NSCLC cell lines results in increased expression of hsa-miR29b. Surprisingly, we also identify specific regulation of hsa-miR29b by Wnt7a but not by Wnt3, a ligand for β-catenin-dependent signaling. Interestingly, knockdown of hsa-miR29b was enough to abrogate the tumor suppressive effects of Wnt7a/Frizzled9 signaling in NSCLC cells, suggesting that hsa-miR29b is an important mediator of β-catenin independent signaling. Finally, we show for the first time that hsa-miR29b plays an important role as a tumor suppressor in lung cancer by targeting murine double mutant 2 (MDM2), revealing novel nodes for Wnt7a/Frizzled9-mediated regulation of NSCLC cell proliferation.

Marybeth Sechler,1,2 Amber D Cizmic,3 Sreedevi Avasarala,1 Michelle Van Scoyk,1 Christine Brzezinski,1 Nicole Kelley,1 Rama Kamesh Bikkavilli,1 Robert A Winn1–3 1Division of Pulmonary Sciences and Critical Care, 2Program in Cancer Biology, University of Colorado, Aurora, CO, USA; 3Veterans Affairs Medical Center, Denver, CO, USA Abstract: Targeted therapies for cancer bring the hope of specific treatment, providing high efficacy and in some cases lower toxicity than conventional treatment. Although targeted therapeutics have helped immensely in the treatment of several cancers, like chronic myelogenous leukemia, colon cancer, and breast cancer, the benefit of these agents in the treatment of lung cancer remains limited, in part due to the development of drug resistance. In this review, we discuss the mechanisms of drug resistance and the current strategies used to treat lung cancer. A better understanding of these drug-resistance mechanisms could potentially benefit from the development of a more robust personalized medicine approach for the treatment of lung cancer. Keywords: lung cancer, drug targets, personalized medicine, NSCLC

This study seeks to understand distance from health facilities as a barrier to maternal and child health service uptake within a rural Liberian population. Better understanding the relationship between distance from health facilities and rural health care utilization is important for post–Ebola health systems reconstruction and for general rural health system planning in sub–Saharan Africa.