Evolution of MIR168 paralogs in Brassicaceae

<p>Abstract</p> <p>Background</p> <p>In plants, expression of ARGONAUTE1 (AGO1), the catalytic subunit of the RNA-Induced Silencing Complex responsible for post-transcriptional gene silencing, is controlled through a feedback loop involving the miR168 microRNA. This complex auto-regulatory loop, composed of miR168-guided AGO1-catalyzed cleavage of <it>AGO1 </it>mRNA and AGO1-mediated stabilization of miR168, was shown to ensure the maintenance of AGO1 homeostasis that is pivotal for the correct functioning of the miRNA pathway.</p> <p>Results</p> <p>We applied different approaches to studying the genomic organization and the structural and functional evolution of <it>MIR168 </it>homologs in Brassicaeae. A whole genome comparison of Arabidopsis and poplar, phylogenetic footprinting and phylogenetic reconstruction were used to date the duplication events originating <it>MIR168 </it>homologs in these genomes. While orthology was lacking between Arabidopsis and poplar <it>MIR168 </it>genes, we successfully isolated orthologs of both loci present in Arabidopsis (<it>MIR168a </it>and <it>MIR168b</it>) from all the Brassicaceae species analyzed, including the basal species <it>Aethionema grandiflora</it>, thus indicating that (1) independent duplication events took place in Arabidopsis and poplar lineages and (2) the origin of <it>MIR168 </it>paralogs predates both the Brassicaceae radiation and the Arabidopsis alpha polyploidization. Different phylogenetic footprints, corresponding to known functionally relevant regions (transcription starting site and double-stranded structures responsible for microRNA biogenesis and function) or for which functions could be proposed, were found to be highly conserved among <it>MIR168 </it>homologs. Comparative predictions of the identified microRNAs also indicate extreme conservation of secondary structure and thermodynamic stability.</p> <p>Conclusion</p> <p>We used a comparative phylogenetic footprinting approach to identify the structural and functional constraints that shaped <it>MIR168 </it>evolution in Brassicaceae. Although their duplication happened at least 40 million years ago, we found evidence that both <it>MIR168 </it>paralogs have been maintained throughout the evolution of Brassicaceae, most likely functionally as indicated by the extremely high conservation of functionally relevant regions, predicted secondary structure and thermodynamic profile. Interestingly, the expression patterns observed in Arabidopsis indicate that <it>MIR168b </it>underwent partial subfunctionalization as determined by the experimental characterization of its expression pattern provided in this study. We found further evolutionary evidence that pre-miR168 lower stem (the RNA-duplex structure adjacent to the miR-miR* stem) is significantly longer than animal lower stems and probably plays a relevant role in multi-step miR168 biogenesis.</p

Channel formation and visualization of melting and crystallization behaviors in direct‐contact latent heat storage systems

Thermal storage systems are an essential component for increasing the share of renewable energies in residential heating and for the valorization of waste heat. A key challenge for the widespread application of thermal storage systems is their limited power‐to‐capacity ratio. One potential solution for this challenge is represented by direct‐contact latent heat storage systems, in which a phase change material (PCM) is in direct contact with an immiscible heat transfer fluid (HTF). To demonstrate the applicability of the direct‐contact concept for domestic hot water production, a PCM with a phase change temperature of 59°C is chosen. To enable cost‐efficient implementation of the storage system, a eutectic mixture of two salt hydrates, magnesium chloride hexahydrate and magnesium nitrate hexahydrate, is chosen as the PCM. One key aspect for the direct‐contact concept is that, during discharge, the HTF channels in the PCM do not become clogged during the solidification of the PCM. In this study, the formation and topology of the channels in direct‐contact systems under an optimized flow condition are investigated via visual observation and X‐ray computed tomography. The elucidation of the channel structure provides information on the melting and crystallization behaviors of the PCM, which are shown schematically

Clinical Study Routine Follow-Up Cranial Computed Tomography for Deeply Sedated, Intubated, and Ventilated Multiple Trauma Patients with Suspected Severe Head Injury

Background. Missed or delayed detection of progressive neuronal damage after traumatic brain injury (TBI) may have negative impact on the outcome. We investigated whether routine follow-up CT is beneficial in sedated and mechanically ventilated trauma patients. Methods. The study design is a retrospective chart review. A routine follow-up cCT was performed 6 hours after the admission scan. We defined 2 groups of patients, group I: patients with equal or recurrent pathologies and group II: patients with new findings or progression of known pathologies. Results. A progression of intracranial injury was found in 63 patients (42%) and 18 patients (12%) had new findings in cCT 2 (group II). In group II a change in therapy was found in 44 out of 81 patients (54%). 55 patients with progression or new findings on the second cCT had no clinical signs of neurological deterioration. Of those 24 patients (44%) had therapeutic consequences due to the results of the follow-up cCT. Conclusion. We found new diagnosis or progression of intracranial pathology in 54% of the patients. In 54% of patients with new findings and progression of pathology, therapy was changed due to the results of follow-up cCT. In trauma patients who are sedated and ventilated for different reasons a routine follow-up CT is beneficial

Demography and mating system shape the genome-wide impact of purifying selection in Arabis alpina

YesPlant mating systems have profound effects on levels and structuring of genetic variation and can affect the impact of natural selection. Although theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study the effect of mating system on purifying selection by conducting population-genomic analyses on whole-genome resequencing data from 38 European individuals of the arctic-alpine crucifer Arabis alpina. We find that outcrossing and mixed-mating populations maintain genetic diversity at similar levels, whereas highly self-fertilizing Scandinavian A. alpina show a strong reduction in genetic diversity, most likely as a result of a postglacial colonization bottleneck. We further find evidence for accumulation of genetic load in highly self-fertilizing populations, whereas the genome-wide impact of purifying selection does not differ greatly between mixed-mating and outcrossing populations. Our results demonstrate that intermediate levels of outcrossing may allow efficient selection against harmful alleles, whereas demographic effects can be important for relaxed purifying selection in highly selfing populations. Thus, mating system and demography shape the impact of purifying selection on genomic variation in A. alpina. These results are important for an improved understanding of the evolutionary consequences of mating system variation and the maintenance of mixed-mating strategies.This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707492115/-/DCSupplemental

Effects of general practitioner training and family support services on the care of home-dwelling dementia patients - Results of a controlled cluster-randomized study

<p>Abstract</p> <p>Background</p> <p>More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. <it>Objective: </it>To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups.</p> <p>Method</p> <p>129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services.</p> <p>Results</p> <p>The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing.</p> <p>Conclusion</p> <p>Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Dementia care initiative in primary practice – study protocol of a cluster randomized trial on dementia management in a general practice setting

<p>Abstract</p> <p>Background</p> <p>Current guidelines for dementia care recommend the combination of drug therapy with non-pharmaceutical measures like counselling and social support. However, the scientific evidence concerning non-pharmaceutical interventions for dementia patients and their informal caregivers remains inconclusive. Targets of modern comprehensive dementia care are to enable patients to live at home as long and as independent as possible and to reduce the burden of caregivers. The objective of the study is to compare a complex intervention including caregiver support groups and counselling against usual care in terms of time to nursing home placement. In this paper the study protocol is described.</p> <p>Methods/Design</p> <p>The IDA (Initiative Demenzversorgung in der Allgemeinmedizin) project is designed as a three armed cluster-randomized trial where dementia patients and their informal caregivers are recruited by general practitioners. Patients in the study region of Middle Franconia, Germany, are included if they have mild or moderate dementia, are at least 65 years old, and are members of the German AOK (Allgemeine Ortskrankenkasse) sickness fund. In the control group patients receive regular treatment, whereas in the two intervention groups general practitioners participate in a training course in evidence based dementia treatment, recommend support groups and offer counseling to the family caregivers either beginning at baseline or after the 1-year follow-up. The study recruitment and follow-up took place from July 2005 to January 2009. 303 general practitioners were randomized of which 129 recruited a total of 390 patients. Time to nursing home admission within the two year intervention and follow-up period is the primary endpoint. Secondary endpoints are cognitive status, activities of daily living, burden of care giving as well as healthcare costs. For an economic analysis from the societal perspective, data are collected from caregivers as well as by the use of routine data from statutory health insurance and long-term care insurance.</p> <p>Discussion</p> <p>From a public health perspective, the IDA trial is expected to lead to evidence based results on the community effectiveness of non-pharmaceutical support measures for dementia patients and their caregivers in the primary care sector. For health policy makers it is necessary to make their decisions about financing new services based on strong knowledge about the acceptance of measures in the population and their cost-effectiveness.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Biological Earth observation with animal sensors

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change