Direct and indirect selection on flowering time, water-use efficiency (WUE, δ (13)C), and WUE plasticity to drought in Arabidopsis thaliana.

Flowering time and water-use efficiency (WUE) are two ecological traits that are important for plant drought response. To understand the evolutionary significance of natural genetic variation in flowering time, WUE, and WUE plasticity to drought in Arabidopsis thaliana, we addressed the following questions: (1) How are ecophysiological traits genetically correlated within and between different soil moisture environments? (2) Does terminal drought select for early flowering and drought escape? (3) Is WUE plasticity to drought adaptive and/or costly? We measured a suite of ecophysiological and reproductive traits on 234 spring flowering accessions of A. thaliana grown in well-watered and season-ending soil drying treatments, and quantified patterns of genetic variation, correlation, and selection within each treatment. WUE and flowering time were consistently positively genetically correlated. WUE was correlated with WUE plasticity, but the direction changed between treatments. Selection generally favored early flowering and low WUE, with drought favoring earlier flowering significantly more than well-watered conditions. Selection for lower WUE was marginally stronger under drought. There were no net fitness costs of WUE plasticity. WUE plasticity (per se) was globally neutral, but locally favored under drought. Strong genetic correlation between WUE and flowering time may facilitate the evolution of drought escape, or constrain independent evolution of these traits. Terminal drought favored drought escape in these spring flowering accessions of A. thaliana. WUE plasticity may be favored over completely fixed development in environments with periodic drought

Impact of harvest on switchgrass leaf microbial communities

Switchgrass is a promising feedstock for biofuel production, with potential for leveraging its native microbial community to increase productivity and resilience to environmental stress. Here, we characterized the bacterial, archaeal and fungal diversity of the leaf microbial community associated with four switchgrass (Panicum virgatum) genotypes, subjected to two harvest treatments (annual harvest and unharvested control), and two fertilization levels (fertilized and unfertilized control), based on 16S rRNA gene and internal transcribed spacer (ITS) region amplicon sequencing. Leaf surface and leaf endosphere bacterial communities were significantly different with Alphaproteobacteria enriched in the leaf surface and Gammaproteobacteria and Bacilli enriched in the leaf endosphere. Harvest treatment significantly shifted presence/absence and abundances of bacterial and fungal leaf surface community members: Gammaproteobacteria were significantly enriched in harvested and Alphaproteobacteria were significantly enriched in unharvested leaf surface communities. These shifts were most prominent in the upland genotype DAC where the leaf surface showed the highest enrichment of Gammaproteobacteria, including taxa with 100% identity to those previously shown to have phytopathogenic function. Fertilization did not have any significant impact on bacterial or fungal communities. We also identified bacterial and fungal taxa present in both the leaf surface and leaf endosphere across all genotypes and treatments. These core taxa were dominated by Methylobacterium, Enterobacteriaceae, and Curtobacterium, in addition to Aureobasidium, Cladosporium, Alternaria and Dothideales. Local core leaf bacterial and fungal taxa represent promising targets for plant microbe engineering and manipulation across various genotypes and harvest treatments. Our study showcases, for the first time, the significant impact that harvest treatment can have on bacterial and fungal taxa inhabiting switchgrass leaves and the need to include this factor in future plant microbial community studies

Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation.

An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, 'antagonistic' pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits 'adaptive' pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a 'drought escape' strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch

Salt tolerance QTLs of an endemic rice landrace, \u3ci\u3eHorkuch\u3c/i\u3e at seedling and reproductive stages

Salinity has a significant negative impact on production of rice. To cope with the increased soil salinity due to climate change, we need to develop salt tolerant rice varieties that can maintain their high yield. Rice landraces indigenous to coastal Bangladesh can be a great resource to study the genetic basis of salt adaptation. In this study, we implemented a QTL analysis framework with a reciprocal mapping population developed from a salt tolerant landrace Horkuch and a high yielding rice variety IR29. Our aim was to detect genetic loci that contributes to the salt adaptive responses of the two different developmental stages of rice which are very sensitive to salinity stress. We identified 14 QTLs for 9 traits and found that most are unique to specific developmental stages. In addition, we detected a significant effect of the cytoplasmic genome on the QTL model for some traits such as leaf total potassium and filled grain weight. This underscores the importance of considering cytoplasm-nuclear interaction for breeding programs. Finally, we identified QTLs co-localization for multiple traits that highlights the possible constraint of multiple QTL selection for breeding programs due to different contributions of a donor allele for different traits

Genetic Associations in Four Decades of Multienvironment Trials Reveal Agronomic Trait Evolution in Common Bean

Multienvironment trials (METs) are widely used to assess the performance of promising crop germplasm. Though seldom designed to elucidate genetic mechanisms, MET data sets are often much larger than could be duplicated for genetic research and, given proper interpretation, may offer valuable insights into the genetics of adaptation across time and space. The Cooperative Dry Bean Nursery (CDBN) is a MET for common bean (Phaseolus vulgaris) grown for . 70 years in the United States and Canada, consisting of 20–50 entries each year at 10–20 locations. The CDBN provides a rich source of phenotypic data across entries, years, and locations that is amenable to genetic analysis. To study stable genetic effects segregating in this MET, we conducted genome-wide association studies (GWAS) using best linear unbiased predictions derived across years and locations for 21 CDBN phenotypes and genotypic data (1.2 million SNPs) for 327 CDBN genotypes. The value of this approach was confirmed by the discovery of three candidate genes and genomic regions previously identified in balanced GWAS. Multivariate adaptive shrinkage (mash) analysis, which increased our power to detect significant correlated effects, found significant effects for all phenotypes. Mash found two large genomic regions with effects on multiple phenotypes, supporting a hypothesis of pleiotropic or linked effects that were likely selected on in pursuit of a crop ideotype. Overall, our results demonstrate that statistical genomics approaches can be used on MET phenotypic data to discover significant genetic effects and to define genomic regions associated with crop improvement

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders

OBJECTIVES: We aimed to evaluate optic chiasm (OC) measures as potential imaging marker for anterior optic pathway damage assessment in the context of neuromyelitis optica spectrum disorders (NMOSD). MATERIALS AND METHOD: This cross-sectional study included 39 patients exclusively with aquaporin 4-IgG seropositive NMOSD of which 25 patients had a history of optic neuritis (NMOSD-ON) and 37 age- and sex-matched healthy controls (HC). OC heights, width, and area were measured using standard 3D T1-weighted MRI. Sensitivity of these measures to detect neurodegeneration in the anterior optic pathway was assessed in receiver operating characteristics analyses. Correlation coefficients were used to assess associations with structural measures of the anterior optic pathway (optic nerve dimensions, retinal ganglion cell loss) and clinical measures (visual function and disease duration). RESULTS: OC heights and area were significantly smaller in NMOSD-ON compared to HC (NMOSD-ON vs. HC p < 0.0001). An OC area smaller than 22.5 mm(2) yielded a sensitivity of 0.92 and a specificity of 0.92 in separating chiasms of NMOSD-ON from HC. OC area correlated well with structural and clinical measures in NMOSD-ON: optic nerve diameter (r = 0.4, p = 0.047), peripapillary retinal nerve fiber layer thickness (r = 0.59, p = 0.003), global visual acuity (r = − 0.57, p = 0.013), and diseases duration (r = − 0.5, p = 0.012). CONCLUSION: Our results suggest that OC measures are promising and easily accessible imaging markers for the assessment of anterior optic pathway damage. KEY POINTS: (1) Optic chiasm dimensions were smaller in neuromyelitis optica spectrum disorder patients compared to healthy controls. (2) Optic chiasm dimensions are associated with retinal measures and visual dysfunction. (3) The optic chiasm might be used as an easily accessible imaging marker of neurodegeneration in the anterior optic pathway with potential functional relevance

Low Energy Excitations in Spin Glasses from Exact Ground States

We investigate the nature of the low-energy, large-scale excitations in the three-dimensional Edwards-Anderson Ising spin glass with Gaussian couplings and free boundary conditions, by studying the response of the ground state to a coupling-dependent perturbation introduced previously. The ground states are determined exactly for system sizes up to 12^3 spins using a branch and cut algorithm. The data are consistent with a picture where the surface of the excitations is not space-filling, such as the droplet or the ``TNT'' picture, with only minimal corrections to scaling. When allowing for very large corrections to scaling, the data are also consistent with a picture with space-filling surfaces, such as replica symmetry breaking. The energy of the excitations scales with their size with a small exponent \theta', which is compatible with zero if we allow moderate corrections to scaling. We compare the results with data for periodic boundary conditions obtained with a genetic algorithm, and discuss the effects of different boundary conditions on corrections to scaling. Finally, we analyze the performance of our branch and cut algorithm, finding that it is correlated with the existence of large-scale,low-energy excitations.Comment: 18 Revtex pages, 16 eps figures. Text significantly expanded with more discussion of the numerical data. Fig.11 adde

Mesenchymal stromal cells for treatment of steroid-refractory GvHD : a review of the literature and two pediatric cases

Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B