Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles of tau in the neocortex. We profiled DNA ...methylation in two regions of the cortex from 631 donors, performing an epigenome-wide association study of multiple measures of AD neuropathology. We meta-analyzed our results with those from previous studies of DNA methylation in AD cortex (total n = 2013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated with AD pathology including methylomic variation at loci not previously implicated in dementia. We subsequently profiled DNA methylation in NeuN+ (neuronal-enriched), SOX10+ (oligodendrocyte-enriched) and NeuN-/SOX10- (microglia- and astrocyte-enriched) nuclei, finding that the majority of DMPs identified in 'bulk' cortex tissue reflect DNA methylation differences occurring in non-neuronal cells. Our study highlights the power of utilizing multiple measures of neuropathology to identify epigenetic signatures of AD and the importance of characterizing disease-associated variation in purified cell-types.
Conservation practitioners, policy-makers and researchers work within shared spaces with many shared goals. Improving the flow of information between conservation researchers, practitioners and ...policy-makers could lead to dramatic gains in the effectiveness of conservation practice. However, several barriers can hinder this transfer including lack of time, inaccessibility of evidence, the real or perceived irrelevance of scientific research to practical questions, and the politically motivated spread of disinformation. Conservation Evidence works to overcome these barriers by providing a freely-available database of summarized scientific evidence for the effects of conservation interventions on biodiversity. The methods used to build this database – a combination of discipline-wide literature searching and subject-wide evidence synthesis – have been developed over the last 15 years to address the challenges of synthesizing large volumes of evidence of varying quality and measured outcomes. Here, we describe the methods to enhance understanding of the database and how it should be used. We discuss how the database can help to expand multi-directional information transfers between research, practice and policy, which should improve the implementation of evidence-based conservation and, ultimately, achieve better outcomes for biodiversity.
•Conservation effectiveness could be improved by integrating evidence and practice.•Evidence synthesis helps practitioners by collating multiple studies into reviews.•Conservation Evidence aims to review conservation actions for all taxa and habitats.•We describe the holistic search and synthesis methods used to build the database.•The database could help overcome barriers between research, practice and policy.
Recent studies have suggested a role for epigenetic mechanisms in the complex etiology of various neurodegenerative diseases. In this review, we discuss advances that have been made toward ...understanding the role of epigenetic processes in neurodegenerative disorders, with a particular focus on Alzheimer's disease, where the most extensive studies have been undertaken to date. We provide a brief overview of DNA modifications, followed by a summarization of studies of DNA modifications in Alzheimer's disease and other neurodegenerative diseases.
Epigenetic mechanisms have been hypothesized to play a role in a number of different neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we provide an overview of current studies performed in the field, with a focus on DNA methylation, before discussing the potential direction of future studies.
Hansen's disease (HD), or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to ...improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44-45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plants precisely control lignin deposition in spiral or annular secondary cell wall domains during protoxylem tracheary element (TE) development. Because protoxylem TEs function to transport water ...within rapidly elongating tissues, it is important that lignin deposition is restricted to the secondary cell walls in order to preserve the plasticity of adjacent primary wall domains. The Arabidopsis (Arabidopsis thaliana) inducible VASCULAR NAC DOMAIN7 (VND7) protoxylem TE differentiation system permits the use of mutant backgrounds, fluorescent protein tagging, and high-resolution live-cell imaging of xylem cells during secondary cell wall development. Enzymes synthesizing monolignols, as well as putative monolignol transporters, showed a uniform distribution during protoxylem TE differentiation. By contrast, the oxidative enzymes LACCASE4 (LAC4) and LAC17 were spatially localized to secondary cell walls throughout protoxylem TE differentiation. These data support the hypothesis that precise delivery of oxidative enzymes determines the pattern of cell wall lignification. This view was supported by Iac41ac17 mutant analysis demonstrating that laceases are necessary for protoxylem TE lignification. Overexpression studies showed that laceases are sufficient to catalyze ectopie lignin polymerization in primary cell walls when exogenous monolignols are supplied. Our data support a model of protoxylem TE lignification in which monolignols are highly mobile once exported to the cell wall, and in which precise targeting of laceases to secondary cell wall domains directs lignin deposition.
Response to Bender et al Smith, Rebecca L; Brooke, Christopher B
The Journal of infectious diseases,
12/2021, Letnik:
224, Številka:
11
Journal Article
Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic ...expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity.
The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic DNA with sodium bisulfite; however, this method cannot distinguish between 5-methylcytosine (5mC) ...and 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC is enriched in the brain, although little is known about its genomic distribution and how it differs between anatomical regions and individuals. In this study, we combine oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome-wide patterns of 5hmC in two distinct anatomical regions of the brain from multiple individuals.
We identify 37,145 and 65,563 sites passing our threshold for detectable 5hmC in the prefrontal cortex and cerebellum respectively, with 23,445 loci common across both brain regions. Distinct patterns of 5hmC are identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. Tissue-specific patterns of 5hmC are subsequently confirmed in an independent set of prefrontal cortex and cerebellum samples.
This study represents the first systematic analysis of 5hmC in the human brain, identifying tissue-specific hydroxymethylated positions and genomic regions characterized by inter-individual variation in DNA hydroxymethylation. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to systematically quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders.
For the next generation of nuclear reactors, HTGRs specifically, an unlikely air ingress warrants inclusion in the license applications of many international regulators. Much research on oxidation ...rates of various graphite grades under a number of conditions has been undertaken to address such an event. However, consequences to the reactor result from the microstructural changes to the graphite rather than directly from oxidation. The microstructure is inherent to a graphite's properties and ultimately degradation to the graphite's performance must be determined to establish the safety of reactor design. To understand the oxidation induced microstructural change and its corresponding impact on performance, a thorough understanding of the reaction system is needed. This article provides a thorough review of the graphite-molecular oxygen reaction in terms of kinetics, mass and energy transport, and structural evolution: all three play a significant role in the observed rate of graphite oxidation. These provide the foundations of a microstructurally informed model for the graphite-molecular oxygen reaction system, a model kinetically independent of graphite grade, and capable of describing both the observed and local oxidation rates under a wide range of conditions applicable to air-ingress.
•Critical review of graphite oxidation relevant to a high-temperature gas-cooled reactor.•Assesses oxidation in terms of microstructure and its evolution.•Model is applicable to all nuclear graphites by using a grade independent kinetics model for the graphite-O2 reaction system.
Infanticide is the killing of infants by conspecifics, and may be direct or indirect; and parental or non‐parental. Explanations for such behaviours range from forcing females with young back into ...heat, resource recycling in times of shortage and elimination of competitors. Though moderately well understood in some mammal groups, reports of infanticide in hystricomorph rodents are often contradictory and invariably based on captive observations, raising questions about the naturality of the behaviour and the conclusions derived from them. Here, we report the first wild observation of direct infanticide and cannibalism of two juvenile Azara's Agoutis Dasyptocta azarae by a group of adults in Paraguay, confirming that such behaviours also occur under natural conditions.
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