Gallus GBrowse: a unified genomic database for the chicken

Gallus GBrowse (http://birdbase.net/cgi-bin/gbrowse/gallus/) provides online access to genomic and other information about the chicken, Gallus gallus. The information provided by this resource includes predicted genes and Gene Ontology (GO) terms, links to Gallus In Situ Hybridization Analysis (GEISHA), Unigene and Reactome, the genomic positions of chicken genetic markers, SNPs and microarray probes, and mappings from turkey, condor and zebra finch DNA and EST sequences to the chicken genome. We also provide a BLAT server (http://birdbase.net/cgi-bin/webBlat) for matching user-provided sequences to the chicken genome. These tools make the Gallus GBrowse server a valuable resource for researchers seeking genomic information regarding the chicken and other avian species

Drought imprints on crops can reduce yield loss: Nature\u27s insights for food security

The Midwestern “Corn-Belt” in the United States is the most productive agricultural region on the planet despite being predominantly rainfed. In this region, global climate change is driving precipitation patterns toward wetter springs and drier mid- to late-summers, a trend that is likely to intensify in the future. The lack of precipitation can lead to crop water limitations that ultimately impact growth and yields. Young plants exposed to water stress will often invest more resources into their root systems, possibly priming the crop for any subsequent mid- or late-season drought. The trend toward wetter springs, however, suggests that opportunities for crop priming may lessen in the future. Here, we test the hypothesis that early season dry conditions lead to drought priming in field-grown crops and this response will protect crops against growth and yield losses from late-season droughts. This hypothesis was tested for the two major Midwestern crop, maize and soybean, using high-resolution daily weather data, satellite-derived phenological metrics, field yield data, and ecosystem-scale model (Agricultural Production System Simulator) simulations. The results from this study showed that priming mitigated yield losses from a late season drought of up to 4.0% and 7.0% for maize and soybean compared with unprimed crops experiencing a late season drought. These results suggest that if the trend toward wet springs with drier summers continues, the relative impact of droughts on crop productivity is likely to worsen. Alternatively, identifying opportunities to breed or genetically modify pre-primed crop species may provide improved resilience to future climate change

Use of Annual Phosphorus Loss Estimator (APLE) Model to Evaluate a Phosphorus Index

The Phosphorus (P) Index was developed to provide a relative ranking of agricultural fields according to their potential for P loss to surface water. Recent efforts have focused on updating and evaluating P Indices against measured or modeled P loss data to ensure agreement in magnitude and direction. Following a recently published method, we modified the Maryland P Site Index (MD-PSI) from a multiplicative to a component index structure and evaluated the MD-PSI outputs against P loss data estimated by the Annual P Loss Estimator (APLE) model, a validated, field-scale, annual P loss model. We created a theoretical dataset of fields to represent Maryland conditions and scenarios and created an empirical dataset of soil samples and management characteristics from across the state. Through the evaluation process, we modified a number of variables within the MD-PSI and calculated weighting coefficients for each P loss component. We have demonstrated that our methods can be used to modify a P Index and increase correlation between P Index output and modeled P loss data. The methods presented here can be easily applied in other states where there is motivation to update an existing P Index

Advances in field-based high-throughput photosynthetic phenotyping

Gas exchange techniques revolutionized plant research and advanced understanding, including associated fluxes and efficiencies, of photosynthesis, photorespiration, and respiration of plants from cellular to ecosystem scales. These techniques remain the gold standard for inferring photosynthetic rates and underlying physiology/biochemistry, although their utility for high-throughput phenotyping (HTP) of photosynthesis is limited both by the number of gas exchange systems available and the number of personnel available to operate the equipment. Remote sensing techniques have long been used to assess ecosystem productivity at coarse spatial and temporal resolutions, and advances in sensor technology coupled with advanced statistical techniques are expanding remote sensing tools to finer spatial scales and increasing the number and complexity of phenotypes that can be extracted. In this review, we outline the photosynthetic phenotypes of interest to the plant science community and describe the advances in high-throughput techniques to characterize photosynthesis at spatial scales useful to infer treatment or genotypic variation in field-based experiments or breeding trials. We will accomplish this objective by presenting six lessons learned thus far through the development and application of proximal/remote sensing-based measurements and the accompanying statistical analyses. We will conclude by outlining what we perceive as the current limitations, bottlenecks, and opportunities facing HTP of photosynthesis

To have value, comparisons of high-throughput phenotyping methods need statistical tests of bias and variance

The gap between genomics and phenomics is narrowing. The rate at which it is narrowing, however, is being slowed by improper statistical comparison of methods. Quantification using Pearson’s correlation coefficient (r) is commonly used to assess method quality, but it is an often misleading statistic for this purpose as it is unable to provide information about the relative quality of two methods. Using r can both erroneously discount methods that are inherently more precise and validate methods that are less accurate. These errors occur because of logical flaws inherent in the use of r when comparing methods, not as a problem of limited sample size or the unavoidable possibility of a type I error. A popular alternative to using r is to measure the limits of agreement (LOA). However both r and LOA fail to identify which instrument is more or less variable than the other and can lead to incorrect conclusions about method quality. An alternative approach, comparing variances of methods, requires repeated measurements of the same subject, but avoids incorrect conclusions. Variance comparison is arguably the most important component of method validation and, thus, when repeated measurements are possible, variance comparison provides considerable value to these studies. Statistical tests to compare variances presented here are well established, easy to interpret and ubiquitously available. The widespread use of r has potentially led to numerous incorrect conclusions about method quality, hampering development, and the approach described here would be useful to advance high throughput phenotyping methods but can also extend into any branch of science. The adoption of the statistical techniques outlined in this paper will help speed the adoption of new high throughput phenotyping techniques by indicating when one should reject a new method, outright replace an old method or conditionally use a new method

Training highly qualified health research personnel: The Pain in Child Health consortium

Background and Objectives: Pain in Child Health (PICH) is a transdisciplinary, international research training consortium. PICH has been funded since 2002 as a Strategic Training Initiative in Health Research of the Canadian Institutes of Health Research, with contributions from other funding partners and the founding participation of five Canadian universities. The goal of PICH has been to create a community of scholars in pediatric pain to improve child health outcomes. Methods: Quantitative analyses enumerated PICH faculty, trainees, training activities and scientific outputs. Interviews with PICH stakeholders were analyzed using qualitative methods capturing perceptions of the program’s strengths, limitations, and opportunities for development and sustainability. Results : PICH has supported 218 trainee members from 2002 through 2013, from 14 countries and more than 16 disciplines. The faculty at the end of 2013 comprised nine co-principal investigators, 14 Canadian coinvestigators, and 28 Canadian and international collaborators. Trainee members published 697 peer-reviewed journal articles on pediatric pain through 2013, among other research dissemination activities including conference presentations and webinars. Networks have been established between new and established researchers across Canada and in 13 other countries. Perceptions from stakeholders commended PICH for its positive impact on the development of pediatric pain researchers. Stakeholders emphasized skills and abilities gained through PICH, the perceived impact of PICH training on this research field, and considerations for future training in developing researchers in pediatric pain. Conclusions: PICH has been successfully developing highly qualified health research personnel within a Canadian and international community of pediatric pain scholarship

Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumor microenvironment (TME) of 162 HNSCC primary tumors of diverse etiologic and spatial origin, through gene expression and IHC profiling of relevant immune proteins, T-cell receptor (TCR) repertoire analysis, and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (i) cytotoxic, (ii) plasma cell rich, (iii) dendritic cell rich, (iv) macrophage rich, and (v) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T-cell infiltration and immune checkpoint expression (e.g., PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history, and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents. // Significance: Here we present our findings on the genomic and immune landscape of primary disease in a cohort of 162 patients with HNSCC, benefitting from detailed molecular and clinical characterization. By employing whole-exome sequencing and gene expression analysis of relevant immune markers, TCR profiling, and staining of relevant proteins involved in immune response, we highlight how distinct etiologies, cell intrinsic, and environmental factors combine to shape the landscape of HNSCC primary disease

Chronic diseases and multi-morbidity - a conceptual modification to the WHO ICCC model for countries in health transition

Background: The burden of non-communicable diseases is rising, particularly in low and middle-income countries undergoing rapid epidemiological transition. In sub-Saharan Africa, this is occurring against a background of infectious chronic disease epidemics, particularly HIV and tuberculosis. Consequently, multi-morbidity, the co-existence of more than one chronic condition in one person, is increasing; in particular multimorbidity due to comorbid non-communicable and infectious chronic diseases (CNCICD). Such complex multimorbidity is a major challenge to existing models of healthcare delivery and there is a need to ensure integrated care across disease pathways and across primary and secondary care. Discussion: The Innovative Care for Chronic Conditions (ICCC) Framework developed by the World Health Organization provides a health systems roadmap to meet the increasing needs of chronic disease care. This framework incorporates community, patient, healthcare and policy environment perspectives, and forms the cornerstone of South Africa’s primary health care re-engineering and strategic plan for chronic disease management integration. However, it does not significantly incorporate complexity associated with multimorbidity and CNCICD. Using South Africa as a case study for a country in transition, we identify gaps in the ICCC framework at the micro-, meso-, and macro-levels. We apply the lens of CNCICD and propose modification of the ICCC and the South African Integrated Chronic Disease Management plan. Our framework incorporates the increased complexity of treating CNCICD patients, and highlights the importance of biomedicine (biological interaction). We highlight the patient perspective using a patient experience model that proposes that treatment adherence, healthcare utilization, and health outcomes are influenced by the relationship between the workload that is delegated to patients by healthcare providers, and patients’ capacity to meet the demands of this workload. We link these issues to provider perspectives that interact with healthcare delivery and utilization. Summary: Our proposed modification to the ICCC Framework makes clear that healthcare systems must work to make sense of the complex collision between biological phenomena, clinical interpretation, beliefs and behaviours that follow from these. We emphasize the integration of these issues with the socio-economic environment to address issues of complexity, access and equity in the integrated management of chronic diseases previously considered in isolation

Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis

Aims: Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis. Methods and results: TRPM7-deficient mice with deletion of the kinase domain (TRPM7+/Δkinase) were studied and molecular mechanisms investigated in TRPM7+/Δkinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGFβ) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-α] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+/Δkinase mice. These processes were associated with infiltration of inflammatory cells (F4/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+/Δkinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+/Δkinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+/Δkinase mice. TRPM7+/Δkinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+/Δkinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGFβ in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment. Conclusions: We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes