DNA Methylation Differences in Monozygotic Twin Pairs Discordant for Schizophrenia Identifies Psychosis Related Genes and Networks

Background Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. Methods We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. Results The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; “cell death and survival” and a “cellular movement and immune cell trafficking”. These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. Conclusions The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia

First Demonstration of Electrostatic Damping of Parametric Instability at Advanced LIGO

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

“Friday is my research day”: chance, time and desire in the search for the teaching-research nexus in the life of a university teacher

This paper builds on some ideas recently presented by Boyd et al. (2010). In that paper, the focus was on the ways in which experienced academic staff articulate the teaching-research nexus. By presenting six short case accounts, this paper describes how a reflective narrative activity enabled some ‘new to academe’ teachers to identify the teaching research nexus in their own work. For each of them, there was some particular reason or stimulus that led to them articulating the teaching-learning nexus in their work. Given the effectiveness of this method for enabling staff to consider the teaching-research nexus, this paper speculates on ways of drawing all academic staff to encounter the ‘concept’ of the teaching-research nexus

Characterization of a Mud Deposit Offshore of the Patos Lagoon, Southern Brazil

Rapid deposition of mud on the beach along the shoreface of Rio Grande do Sul, Brazil dramatically influences the normal operations in the littoral zone. In the surf zone, fluid and suspended mud opposes water-wave movement and dissipates water-wave energy; on the beach, mud limits trafficability. As part of a multinational, multidisciplinary program to evaluate the influence of mud strength, density and viscosity on water-wave attenuation, sediments were evaluated in situ or collected for evaluation from an area offshore of Cassino Beach, slightly south of the Patos Lagoon mouth. Shear strength of deposited sediments ranged from 0.6 kPa at the seafloor to 3.4 kPa at similar to 1 m below the seafloor. Mud sediments were also collected to simulate the in situ response of fluid mud to shear stresses. For this determination, theological evaluations were made using a strain-controlled Couette viscometer on numerous remixed samples that ranged in density from 1.05 to 1.30 g/cm(3). it was determined that this mud is a non-ideal Bingham material in that it has a true initial yield stress as well as a upper Bingham yield stress. Initial yield stress ranged from 0.59 to 2.62 Pa, upper Bingham yield stress ranged from 1.05 to 7.6 Pa. Apparent viscosity ranged from 0.02 to 4.7 Pa s with the highest viscosities occurring between the two yield stresses. Sediment strength in the remixed samples is 2 to 3 orders of magnitude lower than the horizontal shear strength of the sediment bed as determined by shear vane or predicted from penetrometer measurements. This difference is partially due to the fact that rheological evaluations are made on fully remixed sediments, whereas horizontal shear strength is determined within relatively undisturbed sediments. Similar values of viscosity and shear strength are comparable to those determined for mud in other coastal areas where fluid mud deposits occur. (C) 2009 Elsevier Ltd. All rights reserved

High Pressure Processing of Dairy Foods

End of Project ReportThe term High Pressure Processing (HPP) is used to describe the technology whereby products are exposed to very high pressures in the region of 50 - 800 MPa (500 - 8000 Atmospheres). The potential application of HPP in the food industry has gained popularity in recent years, due to developments in the construction of HPP equipment which makes the technology more affordable. Applying HPP to food products results in modifications to interactions between individual components, rates of enzymatic reactions and inactivation of micro-organisms. The first commercial HPP products appeared on the market in 1991 in Japan, where HPP is now being used commercially for products such as jams, sauces, fruit juices, rice cakes and desserts. The pioneering research into the application of HPP to milk dates back to the end of the 19th century. Application of HPP to milk has been shown to modify its gel forming characteristics as well as reducing its microbial load. HPP offers the potential to induce similar effects to those generated by heat on milk protein. Recent reports have also indicated that HPP could accelerate the ripening of cheese. Much of the Irish cheese industry is based on the production of Cheddar cheese, the ripening time for which can vary from 4 - 12 months or more, depending on grade. A substantial portion of the cost associated with Cheddar manufacture is therefore attributed to storage under controlled conditions during ripening. Thus, any technology which may accelerate the ripening of Cheddar cheese while maintaining a balanced flavour and texture is of major economic significance. While food safety is a dominant concern, consumers are increasingly demanding foods that maintain their natural appearance and flavour, while free of chemical preservatives. HPP offers the food industry the possibility of achieving these twin goals as this technology can lead to reduced microbial loads without detrimentally effecting the nutritional or sensory qualities of the product. The development of food ingredients with novel functional properties offers the dairy industry an opportunity to revitalise existing markets and develop new ones. HPP can lead to modifications in the structure of milk components, in particular protein, which may provide interesting possibilities for the development of high value nutritional and functional ingredients. Hence these projects set out to investigate the potential of HPP in the dairy industry and to identify products and processes to which it could be applied.Department of Agriculture, Food and the Marin

Providing Epidemiologic Data in Lumbar Spine Imaging Reports Did Not Affect Subsequent Utilization of Spine Procedures: Secondary Outcomes from a Stepped-Wedge Randomized Controlled Trial

OBJECTIVE: To evaluate the effect of inserting epidemiologic information into lumbar spine imaging reports on subsequent non-surgical and surgical procedures involving the thoracolumbosacral spine and sacroiliac (SI) joints. DESIGN: Analysis of secondary outcomes from the Lumbar Imaging with Reporting of Epidemiology (LIRE) pragmatic stepped-wedge randomized trial. SETTING: Primary care clinics within four integrated healthcare systems in the United States. SUBJECTS: 238,886 patients aged ≥18 years who received lumbar diagnostic imaging between 2013-2016. METHODS: Clinics were randomized to receive text containing age- and modality-specific epidemiologic benchmarks indicating the prevalence of common spine imaging findings in people without low back pain, inserted into lumbar spine imaging reports (the LIRE intervention ). The study outcomes were receiving (1) any non-surgical lumbosacral or sacroiliac spine procedure (lumbosacral epidural steroid injection, facet joint injection, or facet joint radiofrequency ablation; or sacroiliac joint injection) or (2) any surgical procedure involving the lumbar, sacral, or thoracic spine (decompression surgery or spinal fusion or other spine surgery). RESULTS: The LIRE intervention was not significantly associated with subsequent utilization of non-surgical lumbosacral or sacroiliac spine procedures (odds ratio [OR]=1.01, 95% confidence interval [CI] 0.93-1.09; p = 0.79) or any surgical procedure (OR = 0.99, 95 CI 0.91-1.07; p = 0.74) involving the lumbar, sacral, or thoracic spine. The intervention was also not significantly associated with any individual spine procedure. CONCLUSIONS: Inserting epidemiologic text into spine imaging reports had no effect on non-surgical or surgical procedure utilization among patients receiving lumbar diagnostic imaging

Stages of condom use in a high HIV-risk sample

The goals were to (1) clarify high risk individuals into one of five stages of readiness for consistent condom use based on the Transtheoretical Model of behavior change (e.g., Prochaska, Norcross and DiClemente, 1994); (2) investigate whether frequency of condom use was different for vaginal vs. anal sex, and for steady vs. other partners; and (3) explore whether condom use was related to several demographic variables. Street interviews were conducted in six major geographic areas across the United States on a diverse sample of 345 individuals engaging in high HIV-risk behaviors. Percentages of individuals found in each of five stages of condom use were: 36% Precontemplators, 15% Contemplators, 7% in Preparation, 7% in Action, and 35% in Maintenance. Individuals used condoms more with other, casual partners than with a steady partner, and slightly more when engaging in anal sex rather than vaginal sex. Condoms were also used more by: men, Caucasians, non-heterosexuals, and those who were not in a steady relationship than by others not in these categories. Still, the majority of high-risk individuals were not using condoms and were not prepared to start. This presents an urgent need for effective interventions to encourage condom use

Aberrant T-cell exhaustion in SCID survivors with poor T-cell reconstitution post transplant

BACKGROUND: Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes. OBJECTIVE: We hypothesized that CD4+ T-cell lymphopenia could be associated with a state of T-cell exhaustion in previously transplanted SCID patients. METHODS: We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years post-HCT. RESULTS: Compared to post-HCT SCID patients with normal CD4+ T-cell counts, those with poor T-cell reconstitution showed lower frequency of naïve CD45RA+/CCR7+ T cells, recent thymic emigrants (RTEs), and T-cell receptor excision circles (TRECs). They also had a restricted TCR repertoire, increased expression of inhibitory receptors (PD1, 2B4, CD160, BTLA, CTLA-4), and increased activation markers (HLA-DR, perforin) on their total and naïve CD8+ T cells, suggesting T-cell exhaustion and aberrant activation, respectively. The exhaustion score of CD8+ T cells was inversely correlated with CD4+ T-cell count, RTEs, TRECs, and TCR diversity. Exhaustion scores were higher among recipients of unconditioned HCT, especially when further in time from HCT. Patients with fewer CD4+ T cells showed a transcriptional signature of exhaustion. CONCLUSION: Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion due to diminished production of T-lineage cells. Elevated expression of inhibitory receptors on their T cells may be a biomarker of poor long-term T-cell reconstitution. CLINICAL IMPLICATIONS: Hematopoietic cell transplantation for severe combined immunodeficiency may require conditioning to guarantee durable production of new T cells, preventing development of CD4+ T-cell lymphopenia and CD8+ T-cell exhaustion

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p\u3c0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p\u3c0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences