Unusual appearance of a pendulated gastric tumor : always think of GIST

Objective. To investigate the clinicopathological characteristics of gastrointestinal stromal tumor (GIST) with significant cystic changes and to assess the molecular genetic characteristics. Methods. In a 68-year-old man, a large abdominal tumoral mass was discovered incidentally. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a large cystic lesion with multiple contrast-enhancing septae and papillary projections. No clear connection with any of the surrounding organs was identified. Malignancy could not be excluded, and surgery was indicated. During surgery, the large mass was found to be attached by a narrow stalk to the large curvature of the stomach. Results. The histological features and immunohistiochemical profile of the tumor cells (positivity for CD117 and CD34) were consistent with a gastrointestinal stromal tumor with a high risk of progressive disease according to the Fletcher classification. Diagnosis was confirmed by mutational analysis; this demonstrated mutation in exon 14 of PDGFRA. During the followup of 97 months, the patient had a cancer-free survival. Conclusions. This case demonstrates that gastrointestinal stromal tumors (GISTs) with extensive cystic degeneration should be considered in the differential diagnosis of a cystic abdominal mass

Gendered self-views across 62 countries: A test of competing models

Social role theory posits that binary gender gaps in agency and communion should be larger in less egalitarian countries, reflecting these countries’ more pronounced sex-based power divisions. Conversely, evolutionary and self-construal theorists suggest that gender gaps in agency and communion should be larger in more egalitarian countries, reflecting the greater autonomy support and flexible self-construction processes present in these countries. Using data from 62 countries (N = 28,640), we examine binary gender gaps in agentic and communal self-views as a function of country-level objective gender equality (the Global Gender Gap Index) and subjective distributions of social power (the Power Distance Index). Findings show that in more egalitarian countries, gender gaps in agency are smaller and gender gaps in communality are larger. These patterns are driven primarily by cross-country differences in men’s self-views and by the Power Distance Index (PDI) more robustly than the Global Gender Gap Index (GGGI). We consider possible causes and implications of these findings.info:eu-repo/semantics/acceptedVersio

What’s in a surname? Physique, aptitude, and sports type comparisons between Tailors and Smiths

Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Bäumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were not significant. Study 2 examined two large datasets (Austria/Germany combined, and UK: N = 7001 and 20532) of men’s national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, implicit egotism as an alternative interpretation of the evidence, and directions for further inquiry are discussed in conclusion

Loss of Sugar Detection by GLUT2 Affects Glucose Homeostasis in Mice

International audienceBACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets

Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome

Transgenic Overexpression of Active Calcineurin in β-Cells Results in Decreased β-Cell Mass and Hyperglycemia

BACKGROUND:Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+) influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+) signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes. METHODOLOGY/PRINCIPAL FINDINGS:To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP)). To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP) mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis. CONCLUSIONS:Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes

Shedding light on plant litter decomposition: Advances, implications and new directions in understanding the role of photodegradation

Litter decomposition contributes to one of the largest fluxes of carbon (C) in the terrestrial biosphere and is a primary control on nutrient cycling. The inability of models using climate and litter chemistry to predict decomposition in dry environments has stimulated investigation of non-traditional drivers of decomposition, including photodegradation, the abiotic decomposition of organic matter via exposure to solar radiation. Recent work in this developing field shows that photodegradation may substantially influence terrestrial C fluxes, including abiotic production of carbon dioxide, carbon monoxide and methane, especially in arid and semi-arid regions. Research has also produced contradictory results regarding controls on photodegradation. Here we summarize the state of knowledge about the role of photodegradation in litter decomposition and C cycling and investigate drivers of photodegradation across experiments using a meta-analysis. Overall, increasing litter exposure to solar radiation increased mass loss by 23% with large variation in photodegradation rates among and within ecosystems. This variation was tied to both litter and environmental characteristics. Photodegradation increased with litter C to nitrogen (N) ratio, but not with lignin content, suggesting that we do not yet fully understand the underlying mechanisms. Photodegradation also increased with factors that increased solar radiation exposure (latitude and litter area to mass ratio) and decreased with mean annual precipitation. The impact of photodegradation on C (and potentially N) cycling fundamentally reshapes our thinking of decomposition as a solely biological process and requires that we define the mechanisms driving photodegradation before we can accurately represent photodegradation in global C and N models. © 2012 US Government

Susceptibility of Pancreatic Beta Cells to Fatty Acids Is Regulated by LXR/PPARα-Dependent Stearoyl-Coenzyme A Desaturase

Chronically elevated levels of fatty acids-FA can cause beta cell death in vitro. Beta cells vary in their individual susceptibility to FA-toxicity. Rat beta cells were previously shown to better resist FA-toxicity in conditions that increased triglyceride formation or mitochondrial and peroxisomal FA-oxidation, possibly reducing cytoplasmic levels of toxic FA-moieties. We now show that stearoyl-CoA desaturase-SCD is involved in this cytoprotective mechanism through its ability to transfer saturated FA into monounsaturated FA that are incorporated in lipids. In purified beta cells, SCD expression was induced by LXR- and PPARα-agonists, which were found to protect rat, mouse and human beta cells against palmitate toxicity. When their SCD was inhibited or silenced, the agonist-induced protection was also suppressed. A correlation between beta cell-SCD expression and susceptibility to palmitate was also found in beta cell preparations isolated from different rodent models. In mice with LXR-deletion (LXRβ-/- and LXRαβ-/-), beta cells presented a reduced SCD-expression as well as an increased susceptibility to palmitate-toxicity, which could not be counteracted by LXR or PPARα agonists. In Zucker fatty rats and in rats treated with the LXR-agonist TO1317, beta cells show an increased SCD-expression and lower palmitate-toxicity. In the normal rat beta cell population, the subpopulation with lower metabolic responsiveness to glucose exhibits a lower SCD1 expression and a higher susceptibility to palmitate toxicity. These data demonstrate that the beta cell susceptibility to saturated fatty acids can be reduced by stearoyl-coA desaturase, which upon stimulation by LXR and PPARα agonists favors their desaturation and subsequent incorporation in neutral lipids

Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

Type 1 diabetes mellitus is caused by immune-mediated destruction of pancreatic beta-cells leading to insulin deficiency, impaired intermediary metabolism, and elevated blood glucose concentrations. While at autoimmune diabetes onset a limited number of beta-cells persist, the cells' regenerative potential and its regulation have remained largely unexplored. Using two mouse autoimmune diabetes models, this study examined the proliferation of pancreatic islet ss-cells and other endocrine and non-endocrine subsets, and the factors regulating that proliferation.We adapted multi-parameter flow cytometry techniques (including DNA-content measurements and 5'-bromo-2'-deoxyuridine [BrdU] incorporation) to study pancreatic islet single cell suspensions. These studies demonstrate that beta-cell proliferation rapidly increases at diabetes onset, and that this proliferation is closely correlated with the diabetic animals' elevated blood glucose levels. For instance, we show that when normoglycemia is restored by exogenous insulin or islet transplantation, the beta-cell proliferation rate returns towards low levels found in control animals, yet surges when hyperglycemia recurs. In contrast, other-than-ss endocrine islet cells did not exhibit the same glucose-dependent proliferative responses. Rather, disease-associated alterations of BrdU-incorporation rates of delta-cells (minor decrease), and non-endocrine islet cells (slight increase) were not affected by blood glucose levels, or were inversely related to glycemia control after diabetes onset (alpha-cells).We conclude that murine beta-cells' ability to proliferate in response to metabolic need (i.e. rising blood glucose concentrations) is remarkably well preserved during severe, chronic beta-cell autoimmunity. These data suggest that timely control of the destructive immune response after disease manifestation could allow spontaneous regeneration of sufficient beta-cell mass to restore normal glucose homeostasis

How robust is the optimistic update bias for estimating self-risk and population base rates?

Humans hold unrealistically optimistic predictions of what their future holds. These predictions are generated and maintained as people update their beliefs more readily when receiving information that calls for adjustment in an optimistic direction relative to information that calls for adjustment in a pessimistic direction. Thus far this update bias has been shown when people make estimations regarding the self. Here, we examine whether asymmetric belief updating also exists when making estimations regarding population base rates. We reveal that while participants update beliefs regarding risk in the population in an asymmetric manner, such valence-dependent updating of base rates can be accounted for by priors. In contrast, we show that optimistic updating regarding the self is a robust phenomenon, which holds even under different empirical definitions of desirable information