Phenotype screening tests for grain skinning

A4NH is led by the International Food Policy Research Institute (IFPRI) and managed along with The Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT), the International Institute of Tropical Agriculture (IITA), the International Livestock Research Institute (ILRI), the London School of Hygiene and Tropical Medicine (LSHTM), and Wageningen University and Research (WUR)

Variation in grain skinning among spring barley varieties induced by a controlled environment misting screen

The current study investigated use of a controlled misting environment to simulate field conditions that have been implicated in high levels of the malting barley defect, grain skinning. More than 200 spring barley varieties were assessed to identify those varieties that were particularly resistant or susceptible to the defect. Relationships between skinning severity and the traits ear length, floret number, grain number and grain weight were examined among the varieties. In a panel of seven varieties chosen as treatment controls, misting was found to significantly increase skinning severity. The misting treatment had no effect on measured ear traits of these varieties. Among the 200 varieties grown under the misting treatment, there was a continuous spectrum of skinning severities, which were not correlated with ear length, floret number, grain number or grain weight. Using the misting treatment, differences in susceptibility to grain skinning could be determined among varieties. As the misting treatment did not affect measured ear traits, and no correlation was found between ear traits and skinning severity among varieties, the effect of misting on skinning severity must be mediated through other physiological characteristics

Clinical registry of dental outcomes in head and neck cancer patients (OraRad): rationale, methods, and recruitment considerations

Background Most head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT. Methods This is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores. Discussion This study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes. Trial registration ClinicalTrials.gov Identifier NCT02057510 , registered 5 February 2014

A LASSO-based approach to analyzing rare variants in genetic association studies

Genetic markers with rare variants are spread out in the genome, making it necessary and difficult to consider them in genetic association studies. Consequently, wisely combining rare variants into “composite” markers may facilitate meaningful analyses. In this paper, we propose a novel approach of analyzing rare variant data by incorporating the least absolute shrinkage and selection operator technique. We applied this method to the Genetic Analysis Workshop 17 data, and our results suggest that this new approach is promising. In addition, we took advantage of having 200 phenotype replications and assessed the performance of our approach by means of repeated classification tree analyses. Our method and analyses were performed without knowledge of the underlying simulating model. Our method identified 38 markers (in 65 genes) that are significantly associated with the phenotype Affected and correctly identified two causal genes, SIRT1 and PDGFD

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses