Pathogen-Inducible Regulatory Element

Qualitative transcriptional regulatory sequences functional in plants, plant tissue and in plant cells for inducible gene expression and quantitative transcriptional regulatory sequences for increasing the transcriptional expression of downstream genetic information in plants, plant tissue and plant cells are disclosed. Also disclosed are methods and recombinant DNA molecules for improving the disease resistance of transgenic plants, especially wherein an inducible promoter controls the expression of a protein capable of evoking the hypersensitive response in a plant

Association between maternal micronutrient status, oxidative stress and common genetic variants in antioxidant enzymes at 15 weeks’ gestation in nulliparous women who subsequently develop pre-eclampsia

Aims: Pre-eclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc and manganese, have previously been linked to pre-eclampsia at time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered prior to pre-eclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Methods: Pre-disease plasma samples (15+1 weeks’ gestation) were obtained from women enrolled in the international SCreening fOr Pregnancy Endpoints (SCOPE) study who subsequently developed pre-eclampsia (n=244), and age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, caeruloplasmin concentrations and activities, antioxidant capacity and markers of oxidative stress were measured by colorimetric assays. Sixty four tagSNPs within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Results: Plasma copper and caeruloplasmin concentrations were modestly, but significantly elevated in women who subsequently developed pre-eclampsia (both P<0.001) compared to controls (median [IQR], copper: 1957.4 [1787, 2177.5] vs. 1850.0 [1663.5, 2051.5] µg/L; caeruloplasmin: 2.5[1.4, 3.2] vs. 2.2[1.2, 3.0] µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for single nucleotide polymorphisms (SNPs) and antioxidant enzyme activity. Conclusions: This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks’ gestation that subsequently developed pre-eclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop pre-eclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the aetiology of pre-eclampsia

LRP1 Receptor Controls Adipogenesis and Is Up-Regulated In Human and Mouse Obese Adipose Tissue

The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARγ, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity

Effectiveness of a training program for police officers who come into contact with people with mental health problems : A pragmatic randomised controlled trial

INTRODUCTION: Police officers frequently come into contact with individuals with mental health problems. Specialist training in this area for police officers may improve how they respond to individuals with mental health problems; however, evidence to support this is sparse. This study evaluated the effectiveness of one bespoke mental health training package for frontline police officers relative to routine training. DESIGN: Pragmatic, two-armed cluster randomised controlled trial in one police force in England. Police stations in North Yorkshire were randomised with frontline police officers receiving either a bespoke mental health training package or routine training. The primary outcome was the number of incidents which resulted in a police response reported to the North Yorkshire Police control room up to six months after delivery of training. Secondary outcomes included: likelihood of incidents using Section 136 of the Mental Health Act; likelihood of incidents having a mental health tag applied; and number of individuals with a mental health warning marker involved in incidents. The appropriateness of mental health tags applied to a random sample of incidents was checked by an independent mental health professional. Routinely collected data were used. RESULTS: Twelve police stations were recruited and randomised (Intervention group n = 6; Control group n = 6), and 249 officers received the bespoke mental health training intervention. At follow-up, a median of 397 incidents were assigned to trial stations in the intervention group, and 498 in the control group. There was no evidence of a difference in the number of incidents with a police response (adjusted incidence rate ratio (IRR) 0.92, 95% CI 0.61 to 1.38, p = 0.69), or in the number of people with mental health warning markers involved in incidents (adjusted IRR 1.39, 95% CI 0.91 to 2.10, p = 0.13) between the intervention and control groups up to six months following the intervention; however, incidents assigned to stations in the intervention group were more likely to have a mental health tag applied to them than incidents assigned to control stations (adjusted odds ratio 1.41, 95% CI 1.16 to 1.71, p = 0.001). The review of 100 incidents suggests that there may be incidents involving individuals with mental health issues that are not being recorded as such (Kappa coefficient 0.65). There was no statistically significant difference in the likelihood of Section 136 of the Mental Health Act being applied to an incident. CONCLUSIONS: The bespoke one day mental health training delivered to frontline officers by mental health professionals did not reduce the number of incidents reported to the police control room up to six months after its delivery; however training may have a positive effect on how the police record incidents involving individuals with mental health problems. Our trial has shown that conducting pragmatic trials within the police setting is feasible and acceptable. There is a wealth of routinely collected police data that can be utilised for research and further collaboration between police forces and academia is encouraged. TRIAL REGISTRATION: ISRCTN (ISRCTN11685602). The authors confirm that all ongoing and related trials for this drug/intervention are registered

Managing Radiation Degradation of CCDs on the Chandra X-Ray Observatory--III

The CCDs on the Chandra X-ray Observatory are vulnerable to radiation damage from low-energy protons scattered off the telescope's mirrors onto the focal plane. Following unexpected damage incurred early in the mission, the Chandra team developed, implemented, and maintains a radiation-protection program. This program--involving scheduled radiation safing during radiation-belt passes, intervention based upon real-time space-weather conditions and radiation-environment modeling, and on-board radiation monitoring with autonomous radiation safing--has successfully managed the radiation damage to the CCDs. Since implementing the program, the charge-transfer inefficiency (CTI) has increased at an average annual rate of only 3.2x 10(exp -6) (2.3 percent) for the front-illuminated CCDs and 1.0x10(exp -6) (6.7 percent) for the back-illuminated CCDs. This paper describes the current status of the Chandra radiation-management program, emphasizing enhancements implemented since the previous papers

Are early social communication skills a harbinger for language development in infants later diagnosed autistic?—A longitudinal study using a standardized social communication assessment

The early emergence of social communication challenges and their impact on language in infants later diagnosed with autism has sparked many early intervention programs that target social communication skills. While research has consistently shown lower scores on social communication assessments in the first year of life, there is limited research at 12-months exploring associations between different dimensions of social communication and later language. Understanding associations between early social communication skills and language would enhance our ability to choose high priority intervention goals that will impact downstream language skills. The current study used a standardized assessment to profile social communication skills across 516 infants with a high (HL) or low likelihood (LL-Neg) for autism (84% White, 60% Male), based on the presence of a sibling with autism in the family. The primary aim of the study was to profile social communication skill development in the second year of life and to evaluate associations between social communication skills and later language. HL infants who met criteria for autism (HL-ASD, N = 81) demonstrated widespread reductions in social communication skills at 12-months compared to HL infants who did not meet criteria for autism (HL-Neg, N = 277) and LL-Neg (N = 158) infants. Across all infants in the study, those with better social communication skills at 12-months had better language at 24-months. However, within group analyses indicated that infants who met criteria for autism did not show this developmental coupling until 24-months-of-age at which point social communication was positively associated with downstream language skills. The cascading pattern of reduced social communication skills as well as overall significant positive associations with later language provide further evidence for the need to support developing social communication skills prior to formal autism diagnosis, a goal that could possibly be reached through pre-emptive interventions

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses

Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust

20 years of research on the Alcator C-Mod tokamak

The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental observation of ion cyclotron range of frequency (ICRF) mode-conversion, ICRF flow drive, demonstration of lower-hybrid current drive at ITER-like densities and fields and, using a set of novel diagnostics, extensive validation of advanced RF codes. Disruption studies on C-Mod provided the first observation of non-axisymmetric halo currents and non-axisymmetric radiation in mitigated disruptions. A summary of important achievements and discoveries are included.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)United States. Dept. of Energy (Cooperative Agreement DE-FG03-94ER-54241)United States. Dept. of Energy (Cooperative Agreement DE-AC02-78ET- 51013)United States. Dept. of Energy (Cooperative Agreement DE-AC02-09CH11466)United States. Dept. of Energy (Cooperative Agreement DE-FG02-95ER54309)United States. Dept. of Energy (Cooperative Agreement DE-AC02-05CH11231)United States. Dept. of Energy (Cooperative Agreement DE-AC52-07NA27344)United States. Dept. of Energy (Cooperative Agreement DE-FG02- 97ER54392)United States. Dept. of Energy (Cooperative Agreement DE-SC00-02060

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235