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"Adams, T"
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Lair of the serpent
Arriving in Cambodia as a teen medical volunteer, Jonathan learns that a fellow volunteer, his friend Delia whom he'd like to get to know better, has been kidnapped by human traffickers.
Book
A synthetic luciferin improves bioluminescence imaging in live mice
The synthetic firefly luciferase substrate CycLuc1 offers brighter bioluminescence and improved imaging in mouse models at lower doses than the standard D-luciferin.
Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate
D
-luciferin to access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luciferin, CycLuc1, improves BLI with existing luciferase reporters and enables imaging in the brain that could not be achieved with
D
-luciferin.
Journal Article
History vs women : the defiant lives that they don't want you to know
\"Looking through the ages and across the globe, [the authors] have reclaimed the stories of twenty-five remarkable women who dared to defy history and change the world around them. From Mongolian wrestlers to Chinese pirates, Native American ballerinas to Egyptian scientists, Japanese novelists to British Prime Ministers, [this book] will reframe the history that you thought you knew\"--Provided by publisher.
Book
Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish
Although the zebrafish is a major model organism, how they determine sex is not well understood. In domesticated zebrafish, sex determination appears to be polygenic, being influenced by multiple genetic factors that may vary from strain to strain, and additionally can be influenced by environmental factors. However, the requirement of germ cells for female sex determination is well documented: animals that lack germ cells, or oocytes in particular, develop exclusively as males. Recently, it has been determined that oocytes are also required throughout the adult life of the animal to maintain the differentiated female state. How oocytes control sex differentiation and maintenance of the sexual phenotype is unknown. We therefore generated targeted mutations in genes for two oocyte produced signaling molecules, Bmp15 and Gdf9 and here report a novel role for Bmp15 in maintaining adult female sex differentiation in zebrafish. Females deficient in Bmp15 begin development normally but switch sex during the mid- to late- juvenile stage, and become fertile males. Additionally, by generating mutations in the aromatase cyp19a1a, we show that estrogen production is necessary for female development and that the function of Bmp15 in female sex maintenance is likely linked to the regulation of estrogen biosynthesis via promoting the development of estrogen-producing granulosa cells in the oocyte follicle.
Journal Article
Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
Journal Article
Spin Transfer Torques in MnSi at Ultralow Current Densities
Spin manipulation using electric currents is one of the most promising directions in the field of spintronics. We used neutron scattering to observe the influence of an electric current on the magnetic structure in a bulk material. In the skyrmion lattice of manganese silicon, where the spins form a lattice of magnetic vortices similar to the vortex lattice in type II superconductors, we observe the rotation of the diffraction pattern in response to currents that are over five orders of magnitude smaller than those typically applied in experimental studies on current-driven magnetization dynamics in nanostructures. We attribute our observations to an extremely efficient coupling of inhomogeneous spin currents to topologically stable knots in spin structures.
Journal Article
Clinical prediction rules
Clinical prediction rules are mathematical tools that are intended to guide clinicians in their everyday decision making. The popularity of such rules has increased greatly over the past few years. This article outlines the concepts underlying their development and the pros and cons of their use
Journal Article
Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases
There is an unmet need for novel blood-based biomarkers that offer timely and accurate diagnostic and prognostic testing in inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic utility of serum calprotectin (SC) in IBD.
A total of 171 patients (n=96 IBD, n=75 non-IBD) were prospectively recruited. A multi-biomarker model was derived using multivariable logistic regression analysis. Cox proportional hazards model was derived to assess the contribution of each variable to disease outcomes.
SC correlated strongly with current biomarkers, including fecal calprotectin (FC) (n=50, ρ=0.50, P=1.6 × 10
). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37 (95% confidence interval (CI): 2.82-34.68), P=4.00 × 10
) compared with other markers (C-reactive protein (CRP): OR 8.52 (95% CI: 2.75-28.63), P=2.80 × 10
); albumin: OR 6.12 (95% CI: 1.82-22.16), P=0.004). In a subset of 50 patients with paired SC and FC, the area under receiver operating characteristic discriminating IBD from controls was better for FC than for SC (0.99, (95% CI 0.87-1.00) and 0.87 (95% CI:0.78-0.97), respectively; P=0.01). At follow-up (median 342 days; interquartile range: 88-563), SC predicted treatment escalation and/or surgery in IBD (hazard ratio (HR) 2.7, 95% CI: 1.1-4.9), in particular Crohn's disease (CD) (HR 4.2, 95% CI 1.2-15.3). A model incorporating SC and either CRP or albumin has a positive likelihood ratio of 24.14 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of cases (95% CI: 43-79%) and 80% (95% CI: 31-94%) in CD if ≥2 blood marker criteria are met.
A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts.
Journal Article
Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks
Targeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 (EZH2), and lysine-specific demethylase 1 (LSD1), and various signaling pathways essential for cancer cell growth and progression. These specific epigenetic regulators were chosen for review due to their targetability via pharmacological intervention and clinical relevance. Several studies have demonstrated improved efficacy from the dual inhibition of the epigenetic regulators and signaling kinases. Overall, the interactions between epigenetic regulators and kinase signaling pathways are likely influenced by several factors, including individual glioma subtypes, preexisting mutations, and overlapping/interdependent functions of the chromatin regulators. The insights gained by understanding how the genome and epigenome cooperate in high-grade gliomas will guide the design of future therapeutic strategies that utilize dual inhibition with improved efficacy and overall survival.
Journal Article