Altered DNA methylation associated with a translocation linked to major mental illness

Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs, DISC1 and DUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

A comprehensive survey of the analytical, numerical and experimental methodologies for dynamics of multibody mechanical systems with clearance or imperfect joints

"Available online 19 December 2017"A comprehensive survey of the literature of the most relevant analytical, numerical, and experimental approaches for the kinematic and dynamic analyses of multibody mechanical systems with clearance joints is presented in this review. Both dry and lubricated clearance joints are addressed here, and an effort is made to include a large number of research works in this particular field, which have been published since the 1960′s. First, the most frequently utilized methods for modeling planar and spatial multibody mechanical systems with clearance joints are analyzed, and compared. Other important phenomena commonly associated with clearance joint models, such as wear, non-smooth behavior, optimization and control, chaos, and uncertainty and links’ flexibility, are then discussed. The main assumptions procedures and conclusions for the different methodologies are also examined and compared. Finally, future developments and new applications of clearance joint modeling and analysis are highlighted.This research was supported in part by the China 111 Project (B16003) and the National Natural Science Foundation of China under Grants 11290151, 11472042 and 11221202. The work was also supported by the Portuguese Foundation for Science and Technology with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941.info:eu-repo/semantics/publishedVersio

The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea

Seagrasses colonized the sea(1) on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet(2). Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes(3), genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae(4) and that is important for ion homoeostasis, nutrient uptake and O-2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming(5,6), to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants(7)

An integrated bioinformatics analysis reveals divergent evolutionary pattern of oil biosynthesis in high- and low-oil plants

Seed oils provide a renewable source of food, biofuel and industrial raw materials that is important for humans. Although many genes and pathways for acyl-lipid metabolism have been identified, little is known about whether there is a specific mechanism for high-oil content in high-oil plants. Based on the distinct differences in seed oil content between four high-oil dicots (20~50%) and three low-oil grasses (<3%), comparative genome, transcriptome and differential expression analyses were used to investigate this mechanism. Among 4,051 dicot-specific soybean genes identified from 252,443 genes in the seven species, 54 genes were shown to directly participate in acyl-lipid metabolism, and 93 genes were found to be associated with acyl-lipid metabolism. Among the 93 dicot-specific genes, 42 and 27 genes, including CBM20-like SBDs and GPT2, participate in carbohydrate degradation and transport, respectively. 40 genes highly up-regulated during seed oil rapid accumulation period are mainly involved in initial fatty acid synthesis, triacylglyceride assembly and oil-body formation, for example, ACCase, PP, DGAT1, PDAT1, OLEs and STEROs, which were also found to be differentially expressed between high- and low-oil soybean accessions. Phylogenetic analysis revealed distinct differences of oleosin in patterns of gene duplication and loss between high-oil dicots and low-oil grasses. In addition, seed-specific GmGRF5, ABI5 and GmTZF4 were predicted to be candidate regulators in seed oil accumulation. This study facilitates future research on lipid biosynthesis and potential genetic improvement of seed oil content

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

iGepros: an integrated gene and protein annotation server for biological nature exploration

<p>Abstract</p> <p>Background</p> <p>In the post-genomic era, transcriptomics and proteomics provide important information to understand the genomes. With fast development of high-throughput technology, more and more transcriptomics and proteomics data are generated at an unprecedented rate. Therefore, requirement of software to annotate those omics data and explore their biological nature arises. In the past decade, some pioneer works were presented to address this issue, but limitations still exist. Fox example, some of these tools offer command line only, which is not suitable for those users with little or no experience in programming. Besides, some tools don’t support large scale gene and protein analysis.</p> <p>Results</p> <p>To overcome these limitations, an integrated gene and protein annotation server named iGepros has been developed. The server provides user-friendly interfaces and detailed on-line examples, so most researchers even those with little or no programming experience can use it smoothly. Moreover, the server provides many functionalities to compare transcriptomics and proteomics data. Especially, the server is constructed under a model-view-control framework, which makes it easy to incorporate more functions to the server in the future.</p> <p>Conclusions</p> <p>In this paper, we present a server with powerful capability not only for gene and protein functional annotation, but also for transcriptomics and proteomics data comparison. Researchers can survey biological characters behind gene and protein datasets and accelerate their investigation of transcriptome and proteome by applying the server. The server is publicly available at <url>http://www.biosino.org/iGepros/</url>.</p

Disability Education in Medical Schools: A Paradigm Shift for Inclusive Care

Disability education for medical students is often insufficient and can contribute to health disparities for people with disabilities. Our interdisciplinary curriculum development team created a longitudinal 4-year disability education model aimed at improving patient care for people with disabilities. Central to our curriculum are progressive sessions aligned with students\u27 medical journey, including three required sessions covering interdisciplinary healthcare teams, implicit bias, health disparities, disability culture, shared decision-making, communication, and self-determination. Through the inclusion of people with disabilities, an interdisciplinary curriculum development team, and trainee-driven advocacy, our longitudinal multi-phasic disability education curriculum seeks to mitigate health disparities. Our innovative approach addresses the gap in disability education, fostering more compassionate and inclusive healthcare practices