Optimal strategies for regional cultivar testing

In undertaking cultivar trials, the variability of the response of the cultivars to the different environments in which they are grown introduces the possibility of release errors and non‐release errors in the decisions made on the basis of the trial results. In this article a model is developed that accounts for the economic costs of those errors as well as the costs of operating the trials, and enables the features of the optimal cultivar testing program to be identified. The model is illustrated by application to wheat cultivar trials in central and southern NSW.Crop Production/Industries,

What’s Right With Men? Gender Role Socialization and Men’s Positive Functioning

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.This study explored relations between conformity to masculine norms, gender role conflict, hope, and psychological well-being among a sample of 389 men from a university, with a predominantly White student body, located in the Midwestern United States. Bivariate correlations revealed that men’s conformity to masculine norms and gender role conflict were positively correlated. Bivariate correlations revealed no significant relations between conformity to masculine norms, trait hope, and psychological well-being. Gender role conflict was associated with decreased hope and psychological well-being. Results of path analysis explained relations between conformity to masculine norms, gender role conflict, trait hope, and psychological well-being. This indicates that gender role conflict may contribute to lower trait hope and psychological well-being for college men. Although several aspects of conformity to masculine norms had positive associations with hope, these relations were significant and negative when men experienced gender role conflict. This work fills an important gap in the literature by examining the unique relations of conformity to masculine norms and gender role conflict to men’s positive functioning. Results are discussed within the context of positive psychological theories including Frederickson’s broaden and build theory of positive emotions, hope theory, Ryff’s model of psychological well-being, and self-determination theory. Implications and future directions are discussed

Performing group-level functional image analyses based on homologous functional regions mapped in individuals

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the localizer to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations. Author summary No two individuals are alike. The size, shape, position, and connectivity patterns of brain functional regions can vary drastically between individuals. While interindividual differences in functional organization are well recognized, to date, standard procedures for functional neuroimaging research still rely on aligning different subjects' data to a nominal average brain based on global brain morphology. We developed an approach to reliably identify homologous functional regions in each individual and demonstrated that aligning data based on these homologous functional regions can significantly improve the study of resting state functional connectivity, task-fMRI activations, and brain-behavior associations. Moreover, we showed that individual differences in size, position, and connectivity of brain functional regions are dissociable, and each can provide nonredundant information in explaining human behavior

Bruton's Tyrosine Kinase Is Required For Lipopolysaccharide-induced Tumor Necrosis Factor α Production

Lipopolysaccharide (LPS), a product of Gram-negative bacteria, is potent mediator of tumor necrosis factor (TNF)α production by myeloid/macrophage cells. Inhibitors capable of blocking the signaling events that result in TNFα production could provide useful therapeutics for treating septic shock and other inflammatory diseases. Broad spectrum tyrosine inhibitors are known to inhibit TNFα production, however, no particular family of tyrosine kinases has been shown to be essential for this process. Here we show that the Bruton's tyrosine kinase (Btk)-deficient mononuclear cells from X-linked agammaglobulinemia patients have impaired LPS-induced TNFα production and that LPS rapidly induces Btk kinase activity in normal monocytes. In addition, adenoviral overexpression of Btk in normal human monocytes enhanced TNFα production. We examined the role of Btk in TNFα production using luciferase reporter adenoviral constructs and have established that overexpression of Btk results in the stabilization of TNFα mRNA via the 3′ untranslated region. Stimulation with LPS also induced the activation of related tyrosine kinase, Tec, suggesting that the Tec family kinases are important components for LPS-induced TNFα production. This study provides the first clear evidence that tyrosine kinases of the Tec family, in particular Btk, are key elements of LPS-induced TNFα production and consequently may provide valuable therapeutic targets for intervention in inflammatory conditions

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

The relationships between golf and health:A scoping review

OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping review. DATA SOURCES: Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts. REVIEW METHODS: A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated