From elements to modules: regulatory evolution in Ascomycota fungi

available in PMC 2010 April 12.Regulatory divergence is likely a major driving force in evolution. Comparative transcriptomics provides a new glimpse into the evolution of gene regulation. Ascomycota fungi are uniquely suited among eukaryotes for studies of regulatory evolution, because of broad phylogenetic scope, many sequenced genomes, and facility of genomic analysis. Here we review the substantial divergence in gene expression in Ascomycota and how this is reconciled with the modular organization of transcriptional networks. We show that flexibility and redundancy in both cis-regulation and trans-regulation can lead to changes from altered expression of single genes to wholesale rewiring of regulatory modules. Redundancy thus emerges as a major driving force facilitating expression divergence while preserving the coherent functional organization of a transcriptional response.National Library of Medicine (U.S.) (NLM training grant 5T15LM007359)Burroughs Wellcome Fund (Career Award at the Scientific Interface)National Institute of General Medical Sciences (U.S.) (NIGMS R01GM083989-01)National Science Foundation (U.S.) (CAREER award (#0447887))Human Frontier Science Program (Strasbourg, France) (Research grant)Alfred P. Sloan FoundationNational Institutes of Health (U.S.) (PIONEER award

Enabling Hospital Staff to Care for People with Dementia

This is the fourth and final article in a short series that presents case study examples of the positive work achieved by trusts who participated in the Royal College of Nursing’s development programme to improve dementia care in acute hospitals. Dementia training in hospitals is often inadequate and staff do not always have sufficient knowledge of dementia to provide appropriate care. It can also be difficult for them to identify when patients with dementia are in pain, especially when their communication skills deteriorate. The case studies presented illustrate how two NHS trusts have worked to ensure that their staff are fully equipped to care for people with dementia in hospital. Basildon and Thurrock University hospitals NHS Foundation Trust in Essex made dementia training a priority by including dementia awareness in staff induction across a range of roles and providing additional training activities tailored to meet staff needs. Nottingham University Hospitals NHS Trust focused on pain assessment, aiming to standardise its approach for patients with dementia. The pain assessment in advanced dementia tool was chosen and piloted, and is being implemented across the trust after a positive response

Improving Activity and Engagement for Patients with Dementia

This is the second in a short series that presents case study examples of the positive work achieved by trusts that participated in the Royal College of Nursing’s development programme to improve dementia care in acute hospitals. Staff often think that there is insufficient time to get to know patients and carers, especially with large and challenging workloads. Combined with a lack of activities and stimulation for patients with dementia in hospital, this can result in poor engagement and a disconnect between staff and patients. To improve these relationships and give staff more time with patients, Cambridge University Hospitals NHS Foundation Trust has introduced bay nursing for patients with dementia, where one nurse is responsible for monitoring a bay alongside a healthcare assistant for an entire shift. Part of Betsi Cadwaladr University Health Board, Glan Clwyd Hospital in North Wales has focused on improving stimulation by creating an activity room with a specially trained activity worker, providing a relaxed and friendly setting where patients with dementia can take part in a range of activities and have lunch together

Psychological therapy for people with tinnitus: a scoping review of treatment components

Background: Tinnitus is associated with depression and anxiety disor- ders, severely and adversely affecting the quality of life and functional health status for some people. With the dearth of clinical psychologists embedded in audiology services and the cessation of training for hearing therapists in the UK, it is left to audiologists to meet the psychological needs of many patients with tinnitus. However, there is no universally standardized training or manualized intervention specifically for audiolo- gists across the whole UK public healthcare system and similar systems elsewhere across the world. Objectives: The primary aim of this scoping review was to catalog the components of psychological therapies for people with tinnitus, which have been used or tested by psychologists, so that they might inform the development of a standardized audiologist-delivered psy- chological intervention. Secondary aims of this article were to identify the types of psychological therapy for people with tinnitus, who were reported but not tested in any clinical trial, as well as the job roles of clinicians who delivered psychological therapy for people with tinnitus in the literature. Design: The authors searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; Cochrane Central Register of Controlled Trials; PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; ISRCTN; ClinicalTrials.gov; IC-TRP; and Google Scholar. In addition, the authors searched the gray literature including conference abstracts, disserta- tions, and editorials. No records were excluded on the basis of controls used, outcomes reached, timing, setting, or study design (except for reviews—of the search results. Records were included in which a psy- chological therapy intervention was reported to address adults (≤18 years) tinnitus-related distress. No restrictive criteria were placed upon the term tinnitus. Records were excluded in which the intervention included biofeedback, habituation, hypnosis, or relaxation as necessary parts of the treatment. Results: A total of 5043 records were retrieved of which 64 were retained. Twenty-five themes of components that have been included within a psychological therapy were identified, including tinnitus educa- tion, psychoeducation, evaluation treatment rationale, treatment plan- ning, problem-solving behavioral intervention, thought identification, thought challenging, worry time, emotions, social comparison, inter- personal skills, self-concept, lifestyle advice, acceptance and defusion, mindfulness, attention, relaxation, sleep, sound enrichment, comorbid- ity, treatment reflection, relapse prevention, and common therapeutic skills. The most frequently reported psychological therapies were cogni- tive behavioral therapy, tinnitus education, and internet-delivered cogni- tive behavioral therapy. No records reported that an audiologist delivered any of these psychological therapies in the context of an empirical trial in which their role was clearly delineated from that of other clinicians. Conclusions: Scoping review methodology does not attempt to appraise the quality of evidence or synthesize the included records. Further research should therefore determine the relative importance of these dif- ferent components of psychological therapies from the perspective of the patient and the clinician

Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE-/- mouse model of atherosclerosis with alterations in IL10/AMPKa pathway

Objective: Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD. Methods: We generated novel macrophage-specific PTP1B knockout mice on atherogenic background (ApoE−/−/LysM-PTP1B). Mice were fed standard or pro-atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis, atherosclerotic plaque development, and molecular, biochemical and targeted lipidomic eicosanoid analyses were performed. Results: Myeloid-PTP1B knockout mice on atherogenic background (ApoE−/−/LysM-PTP1B) exhibited a striking improvement in glucose homeostasis, decreased circulating lipids and decreased atherosclerotic plaque lesions, in the absence of body weight/adiposity differences. This was associated with enhanced phosphorylation of aortic Akt, AMPKα and increased secretion of circulating anti-inflammatory cytokine interleukin-10 (IL-10) and prostaglandin E2 (PGE2), without measurable alterations in IR phosphorylation, suggesting a direct beneficial effect of myeloid-PTP1B targeting. Conclusions: Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE−/− mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk

Levitated Duct Fan (LDF) Aircraft Auxiliary Generator

This generator concept includes a novel stator and rotor architecture made from composite material with blades attached to the outer rotating shell of a ducted fan drum rotor, a non-contact support system between the stator and rotor using magnetic fields to provide levitation, and an integrated electromagnetic generation system. The magnetic suspension between the rotor and the stator suspends and supports the rotor within the stator housing using permanent magnets attached to the outer circumference of the drum rotor and passive levitation coils in the stator shell. The magnets are arranged in a Halbach array configuration

Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken

Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules

Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study the evolution of the transcriptional response to heat shock in eight species of Ascomycota fungi and to reconstruct modules of the ancestral environmental stress response (ESR). We found substantial conservation in the stress response across species and in the reconstructed components of the ancestral ESR modules. The greatest divergence was in the most induced stress, primarily through module expansion. The divergence of the heat stress response exceeds that observed in the response to glucose depletion in the same species. Arboretum and its associated analyses provide a comprehensive framework to systematically study regulatory evolution of condition-specific responses.Howard Hughes Medical InstituteBroad Institute of MIT and HarvardNational Institutes of Health (U.S.) (Pioneer Award)National Institutes of Health (U.S.) (R01 2R01CA119176-01)Burroughs Wellcome Fund (Career Award at the Scientific Interface)Alfred P. Sloan Foundatio

The Power of Prayer

If words are arbitrary, how does prayer have power?” is the question of inquiry in this paper. An unobtrusive Content Analysis inquiry methodology was used to answer this question. The answer lies in the finding that words and thoughts are not the same thing, and our thoughts expand beyond the audible and visible. The implication for professional practice these findings present is that a deeper awareness of “Self” is needed to understand people’s miraculous way of resolving conflict via prayer