CD59 (CD59 molecule, complement regulatory protein)

Review on CD59 (CD59 molecule, complement regulatory protein), with data on DNA, on the protein encoded, and where the gene is implicated

Nuclear Scaffold Attachment Sites within ENCODE Regions Associate with Actively Transcribed Genes

The human genome must be packaged and organized in a functional manner for the regulation of DNA replication and transcription. The nuclear scaffold/matrix, consisting of structural and functional nuclear proteins, remains after extraction of nuclei and anchors loops of DNA. In the search for cis-elements functioning as chromatin domain boundaries, we identified 453 nuclear scaffold attachment sites purified by lithium-3,5-iodosalicylate extraction of HeLa nuclei across 30 Mb of the human genome studied by the ENCODE pilot project. The scaffold attachment sites mapped predominately near expressed genes and localized near transcription start sites and the ends of genes but not to boundary elements. In addition, these regions were enriched for RNA polymerase II and transcription factor binding sites and were located in early replicating regions of the genome. We believe these sites correspond to genome-interactions mediated by transcription factors and transcriptional machinery immobilized on a nuclear substructure

Effectiveness of Mechanisms and Models of Coordination between Organizations, Agencies and Bodies Providing or Financing Health Services in Humanitarian Crises: A Systematic Review.

BACKGROUND: Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes. METHODS: We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach. RESULTS: Of 14,309 identified citations from databases and organizations' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality. CONCLUSION: This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field

Dynamical density functional theory for orientable colloids including inertia and hydrodynamic interactions

Over the last few decades, classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become powerful tools in the study of colloidal fluids. Recently, previous DDFTs for spherically-symmetric particles have been generalised to take into account both inertia and hydrodynamic interactions, two effects which strongly influence non-equilibrium properties. The present work further generalises this framework to systems of anisotropic particles. Starting from the Liouville equation and utilising Zwanzig's projection-operator techniques, we derive the kinetic equation for the Brownian particle distribution function, and by averaging over all but one particle, a DDFT equation is obtained. Whilst this equation has some similarities with DDFTs for spherically-symmetric colloids, it involves a translational-rotational coupling which affects the diffusivity of the (asymmetric) particles. We further show that, in the overdamped (high friction) limit, the DDFT is considerably simplified and is in agreement with a previous DDFT for colloids with arbitrary shape particles.Comment: dynamical density functional theory ; colloidal fluids ; arbitrary-shape particles ; orientable colloid

Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels.

Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD

Haloperidol alters circadian clock gene product expression in the mouse brain.

OBJECTIVES: Circadian rhythms are patterns in behavioural and physiological measures that recur on a daily basis and are driven by an endogenous circadian timekeeping system whose molecular machinery consists of a number of clock genes. The typical anti-psychotic haloperidol has previously been shown to induce significant deficiencies in circadian timing in patients. In this study we examined the impact of haloperidol treatment on molecular components of the circadian clock in the mouse brain. METHODS: We examined how haloperidol treatment, either acute (both at day and night) or chronically over 14 days, alters the expression of three clock gene protein products (PER1, PER2, BMAL1) across the mouse brain by means of immunohistochemistry. RESULTS: Chronic haloperidol treatment significantly decreases the expression levels of PER1 in a number of brain areas, including the hippocampus, the prefrontal and cingulate cerebral cortex and the paraventricular nucleus of the hypothalamus. PER2 expression was only altered in the dentate gyrus and the CA3, and BMAL1 expression was only altered in the paraventricular nucleus of the hypothalamus. CONCLUSION: These data indicate that haloperidol has the potential to alter circadian rhythms via modulation of circadian clock gene expression

Upregulating CD59: a new strategy for protection of neurons from complement-mediated degeneration

An increasing number of studies have shown a critical role for the membrane attack complex, synthesized on activation of the terminal pathway of the complement system, in causing demyelination and neuronal death in neurodegeneration. The aim of this study was to develop a strategy to increase the resistance of neurons to complement damage by modulating the expression of membrane complement regulatory protein CD59, the only inhibitor of the terminal pathway of the complement cascade. We exploited our recent finding that CD59 expression is regulated by the neural-restrictive silencer factor (REST) and designed a novel REST-derived peptide (REST5) containing the nuclear localization domain of the wild-type protein. The effect of REST5 and the mechanism by which it modulates CD59 expression were modelled in neuroblastoma cells transfected with expression constructs, and then confirmed in human neurons differentiated from neural progenitor cells. REST5 increased the expression of CD59 in neurons by fivefold and protected them from complement-mediated lysis spontaneously triggered by neurons. As a source of complement, we used either human serum or conditioned medium from primary human oligodendroglia. This study brings new insight into immunopharmacological research that may serve to inhibit neuronal death triggered by the terminal pathway of complement activation

A role for SC35 and hnRNPA1 in the determination of amyloid precursor protein isoforms

The β-amyloid peptide (Aβ) that accumulates in senile plaques in Alzheimer’s disease is formed by cleavage of the Amyloid Precursor Protein (APP). The APP gene has several intronic Alu elements inserted in either the sense or antisense orientation. In this study, we demonstrate that binding of SC35 and hnRNPA1 to Alu elements on either side of exon 7 in the transcribed pre-mRNA is involved in alternative splicing of APP exons 7 and 8. Neuronal cells transfected with the full-length form of APP secrete higher levels of Aβ than cells transfected with the APP695 isoform lacking exons 7 and 8. Finally, we show that treatment of neuronal cells with estradiol results in increased expression of APP695, SC35, hnRNPA1, and lowers the level of secreted Aβ. An understanding of the regulation of splicing of APP may lead to the identification of new targets for treating Alzheimer’s disease