The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts

Man was created  with the provision of spiritual awareness of the existence of God. When in the course of his life to find a variety of  problems, which he first headed the Lord. From every human being must  feel that awareness.  If then it is collective  awareness  activities conducted in order to meet the spiritual needs that can be implemented together. That is a God given institution called the Assembly of  dzikir. If then the activity was done with a lot of people, over time some of them  do not  know the exact substance  and virtues of the assembly  itself, but just following everyone else  alone. Moreover, many activities that  involve  mass was boarded by-worldly orientation of  material interests, economic and political. Then the activity will become a kind of wetland that can be exploited in the interests of a handful of people. Key words: majelis dzikir, spiritual awareness, mass cultur

Complement in the homeostatic and ischemic brain

The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke

Review: Astrocytes in Alzheimer's disease and other age-associated dementias; a supporting player with a central role.

Astrocytes have essential roles in the central nervous system and are also implicated in the pathogenesis of neurodegenerative disease. Forming non-overlapping domains, astrocytes are highly complex cells. Immunohistochemistry to a variety of proteins can be used to study astrocytes in tissue, labelling different cellular components and subpopulations, including GFAP, ALDH1L1, CD44, NDRG2 and amino acid transporters, but none of these label the entire astrocyte population. Increasing heterogeneity is recognised in the astrocyte population, a complexity that is relevant both to their normal function and pathogenic roles. They are involved in neuronal support, as active components of the tripartite synapse and in cell interactions within the neurovascular unit, where they are essential for blood brain barrier maintenance and neurovascular coupling. Astrocytes change with age, and their responses may modulate the cellular effects of neurodegenerative pathologies, which alone do not explain all of the variance in statistical models of neurodegenerative dementias. Astrocytes respond to both the neurofibrillary tangles and plaques of Alzheimer's disease, to hyperphosphorylated tau and Aβ, eliciting an effect which may be neuroprotective or deleterious. Astrocyte hypertrophy, in the form of gliosis, occurs, but also astrocyte injury and atrophy. Loss of normal astrocyte functions may contribute to reduced support for neurons and dysfunction of the neurovascular unit. Understanding how astrocytes contribute to dementia requires an understanding of the underlying heterogeneity of astrocyte populations, and the complexity of their responses to pathology. Enhancing the supportive and neuroprotective components of the astrocyte response has potential translational applications in therapeutic approaches to dementia. This article is protected by copyright. All rights reserved

Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation

BACKGROUND: CpG methylation variation is involved in human trait formation and disease susceptibility. Analyses within populations have been biased towards CpG-dense regions through the application of targeted arrays. We generate whole-genome bisulfite sequencing data for approximately 30 adipose and blood samples from monozygotic and dizygotic twins for the characterization of non-genetic and genetic effects at single-site resolution. RESULTS: Purely invariable CpGs display a bimodal distribution with enrichment of unmethylated CpGs and depletion of fully methylated CpGs in promoter and enhancer regions. Population-variable CpGs account for approximately 15–20 % of total CpGs per tissue, are enriched in enhancer-associated regions and depleted in promoters, and single nucleotide polymorphisms at CpGs are a frequent confounder of extreme methylation variation. Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific. Tobacco smoking is associated with differential methylation in blood with no evidence of this exposure impacting cell counts. Opposite to non-genetic effects, genetic effects of CpG methylation are shared across tissues and thus limit inter-tissue epigenetic drift. CpH methylation is rare, and shows similar characteristics of variation patterns as CpGs. CONCLUSIONS: Our study highlights the utility of low pass whole-genome bisulfite sequencing in identifying methylome variation beyond promoter regions, and suggests that targeting the population dynamic methylome of tissues requires assessment of understudied intergenic CpGs distal to gene promoters to reveal the full extent of inter-individual variation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0856-1) contains supplementary material, which is available to authorized users

Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression

INTRODUCTION Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ

An epigenome-wide association study of total serum immunoglobulin E concentration

Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations-with a meta-analysis false discovery rate less than 10(-4)-between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases

Reduction of plant protection products - economic and biological consequences for the pest and weed development in sugar beet-grain-croprotations

Die Diskussion um den Einsatz von Pflanzenschutzmitteln hat in den letzten Jahren auf nationaler Ebene zur Initiierung des Reduktionsprogramms chemischer Pflanzenschutz geführt, in dem gefordert wird, den Pflanzenschutzmitteleinsatz auf das notwendige Maß zu beschränken. Dabei ist das notwendige Maß definiert als die wirtschaftlichste Variante der Befalls bezogenen Pflanzenschutzmittelapplikation. Im Rahmen dieser Arbeit wurden die Möglichkeiten einer Reduktion des Einsatzes von Pflanzenschutzmitteln sowie deren ökonomische und biologische Folgen ausgehend vom heutigen Standard des Pflanzenschutzmitteleinsatzes, der guten fachlichen Praxis analysiert. In 3-jährigen Feldversuchen wurde diese Problemanalyse unter möglichst praxisnahen Bedingungen durchgeführt, um eine Übertragung der Ergebnisse in die landwirtschaftliche Praxis zu prüfen und zu ermöglichen. Im zweiten Teil der Arbeit wurde der Einfluss der Sortenresistenz bei Wintergerste und Winterweizen auf die Möglichkeit der Reduktion des Fungizideinsatzes ermittelt. Im Weizen wurde darüber hinaus der Einfluss einer wendenden und nicht wendenden Bodenbearbeitung auf den Befallsdruck von Krankheiten und dem sich daraus ableitenden Fungizidbedarf untersucht. Die Pflanzenschutzmittelanwendung nach guter fachlicher Praxis zeigte die sicherste insektizide, herbizide und fungizide Wirkung und wies auch den höchsten Gewinn auf. Durch die Anwendung von Expertenwissen und Prognosemodellen wurde demgegenüber der Einsatz von Pflanzenschutzmitteln über die Fruchtfolge um 35 % reduziert. Während die Reduktion in Zuckerrüben unwirtschaftlich war, führte die Reduktion im Getreide gegenüber der guten fachlichen Praxis zu leichten Gewinnen. Eine Reduzierung des Pflanzenschutzmitteleinsatzes um die Hälfte gegenüber der guten fachlichen Praxis führte dagegen zu unbefriedigenden Ergebnissen aus biologischer und ökonomischer Sicht. Der generelle Verzicht auf Pflanzenschutzmittel führte zu starken wirtschaftlichen Verlusten und ist für eine wettbewerbsfähige Landwirtschaft unrealistisch. Durch den Anbau von resistenteren Sorten konnte der Fungizideinsatz um ca. 25 % reduziert werden und zwar schwerpunktmäßig im Winterweizen, wobei der Gesamtaufwand an Pflanzenschutzmitteln dadurch nur um 5 % reduziert wurde. In den Fungizidversuchen im Weizen- und der Gerste konnte gezeigt werden, dass bei Nutzung krankheitsresistenter Sorten im Hinblick auf den Befall bis zu zwei Drittel des Fungizideinsatzes gespart werden konnte. Die Versuche zeigen überdies die Schwierigkeit der Festlegung des optimalen sortenspezifischen Fungizideinsatzes (notwendiges Maß). Im Winterweizen nach nichtwendender Bodenbearbeitung wurde auf Grund des notwendigen protektiven Schutzes gegenüber Drechslera-tritici-repentis 45 % mehr Fungizide in der Expertenvariante eingesetzt. Der Einsatz von Pflanzenschutzmitteln in der Landwirtschaft wird auch zukünftig im Spannungsfeld zwischen ökologischen Interessen, dem Schutz des Naturhaushalts und der Notwendigkeit einer ökonomischen Produktion diskutiert werden müssen