Serial measurements of circulating tissue plastninogen activator and fibrin(ogen) degradation products predict outcome in gestational proteinuric hypertension

Gestational proteinuric hypertension (GPH), a major cause of maternal death, may be characterised by hypertension and proteinuria alone or may progress to disturbed coagulation and multiorgan failure. Since the condition can only be reversed by termination of pregnancy, there is a need for reliable indicators of severity. We found circulating levels of tissue plasminogen activator (tPA)(27,98 ± 2,12 v. 7,17 ± 0,81 ng/ml, mean ± SEM), fibrin(ogen) degradation products (FDP) (7,55 ± 1,99 v. 1,92 ± 0,47 μg/ml) and fibronectin (221 ± 15,2 v. 120 ± 15,2 μg/ml) to be significantly increased in 21 patients with severe GPH when compared with 21 normotensive, age- and gestational age-matched pregnant controls. More importantly, patients who developed severe GPH showed a progressive increase in tPA and FDP levels with time. This was in contrast to patients who had hypertension and proteinuria alone, in whom tPA and FDP concentrations did not increase. Parallel measurements did not reveal a fall in platelet count or an increase in urinary protein excretion in patients who subsequently progressed to severe disease. Our findings may be of assistance to clinicians faced with the need to prolong pregnancy in patients with GPH in order to ensure fetal viability

Association between Regulator of G Protein Signaling 9–2 and Body Weight

Regulator of G protein signaling 9–2 (RGS9–2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9–2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9–2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9–2 as a factor in regulating body weight.National Institute of Mental Health (U.S.) (R41MH78570 award)National Center for Research Resources (U.S.) (Rhode Island IDeA Network of Biomedical Research Excellence (RI-INBRE) Award P20RR016457-10

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

That\u27s Not in the Book! : Narrative Discord from Text to Film

What happens to the reader’s understanding of a text when it is brought to life on the big screen? This session explores narrative changes film adaptations have made to now-classic texts. How do specific changes affect the viewer’s reception of the story, ultimately affecting the “cultural work” the story performs? In her landmark study Sensational Designs, Jane Tompkins argues that the “cultural work” performed by any given text equates to the way in which that text engages with and then alters the fabric of the social world around it. While film adaptations often propel under-recognized stories into the marketplace, film versions, by altering the viewers’ relationship to the original text, also alter the “cultural work” these texts perform, making them less significant in the overall cultural landscape. Specifically, our session focuses on film adaptations where the protagonist becomes more heroic and where the text’s original narrative uncertainty is removed. We highlight the sacrifices a text must make as it is adapted to the screen, explore what effect these sacrifices have upon the viewer, and note how the resulting film adaptations—intended for mainstream market consumption—cheat the viewer out of participatory moments that dilute the text’s potential for affecting social change. For example, when reading Margaret Atwood’s The Handmaid’s Tale or Edgar Allen Poe’s “The Cask of Amontillado,” the reader must determine the narrator’s reliability, timeline, and audience. Film versions of these stories pre-decide such elements, therefore threatening and ultimately changing the reader’s critical connection with the text

Changing the Way We Teach the First-Year Research Project: Intense Collaboration between Reference Librarians and Composition Instructors

When first-year composition students face the traditional research paper, they often struggle to fully engage with the research process. What would happen if reference librarians worked intensively with composition instructors to help students better understand scholarly research? Normally, at Eastern Florida State College, composition students attend one library instruction during the semester to strengthen their informational literacy skills and prepare them to conduct research for the remainder of their academic careers. Our research instruction pilot program changes the current methods in place for library instruction in composition courses and includes the reference librarians as an integral part of the learning process. Our pilot program measures the success of students who receive the benefit of intensive instruction from the reference librarians against those students who receive one classroom-based library session. Our panel will present our collaboration (two instructors and two librarians) over one semester (spring, 2015). We will discuss the particulars of the intensive library instruction, present results of a research pre-test and post-test, and wrap up with our assessment of the process. We expect the students who are exposed to the instructional collaboration to show improvement in the quality of the overall research project. However, we also hope to see a change in the attitudes and confidence levels of those students; this difference in attitude may be cause enough for all composition courses to consider intensive collaborative strategies when tasked with teaching the research paper. Our panel will provide conference participants “real-life” examples of research assignments utilizing our collaborative model

Mixing up the Menu: Info Lit as an Appetizer and not the Main Course

When the primary course for teaching information literacy within the college is not a prerequisite, or even a co-requisite, for your course, what are teachers to do? Often, students focus on gaining information processing skills in their FYW or FYE courses. These core courses are sometimes a misnomer, required to graduate but not necessarily required in the first semester or even the first academic year. Our panel will examine four courses outside of the First-Year Writing sequence, courses where the competencies do not specifically address information literacy (or if so only in tangential ways). Our panel will include four instructors who each teach a different developmental or humanities course. We will talk about strategies we can incorporate into our classroom assignments that promote information literacy skills to students who have perhaps never before completed college-level research for an assignment

Bis[2-(1H-imidazol-2-yl-&amp;#954;N3)-1H-imidazol-3-ium]silver(I) trinitrate

The synthesis of the title salt, [Ag(C6H7N4)2](NO3)3, was carried out employing a 1:2 molar ratio of 2,2&amp;#8242;-biimidazole and silver nitrate respectively. The cation has crystallographically-imposed C2 symmetry with the metal atom in an almost linear coordination environment [N&amp;#8212;Ag&amp;#8212;N = 177.01&amp;#8197;(17)&amp;#176;]. The crystal structure displays N&amp;#8212;H...O and C&amp;#8212;H...O hydrogen-bonding interactions