Integrating Traditional and Social Media Data to Predict Bilateral Migrant Stocks in the European Union

Although up-to-date information on the nature and extent of migration within the European Union (EU) is important for policymaking, timely and reliable statistics on the number of EU citizens residing in or moving across other member states are difficult to obtain. In this paper, we develop a statistical model that integrates data on EU migrant stocks using traditional sources such as census, population registers and Labour Force Survey, with novel data sources, primarily from the Facebook Advertising Platform. Findings suggest that combining different data sources provides near real-time estimates that can serve as early warnings about shifts in EU mobility patterns. Estimated migrant stocks match relatively well to the observed data, despite some overestimation of smaller migrant populations and underestimation for larger migrant populations in Germany and the United Kingdom. In addition, the model estimates missing stocks for migrant corridors and years where no data are available, offering timely now-casted estimates

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

PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Interferon-γ–Induced Pancreatic β-Cell Apoptosis

OBJECTIVE: The pathogenesis of type 1 diabetes has a strong genetic component. Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays a direct role in beta-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal beta-cells, besides evaluating its role in cytokine-induced signaling and beta-cell apoptosis. RESEARCH DESIGN AND METHODS: PTPN2 mRNA and protein expression was evaluated by real-time PCR and Western blot. Small interfering (si)RNAs were used to inhibit the expression of PTPN2 and downstream STAT1 in beta-cells, allowing the assessment of cell death after cytokine treatment. RESULTS: PTPN2 mRNA and protein are expressed in human islets and rat beta-cells and upregulated by cytokines. Transfection with PTPN2 siRNAs inhibited basal- and cytokine-induced PTPN2 expression in rat beta-cells and dispersed human islets cells. Decreased PTPN2 expression exacerbated interleukin (IL)-1beta + interferon (IFN)-gamma-induced beta-cell apoptosis and turned IFN-gamma alone into a proapoptotic signal. Inhibition of PTPN2 amplified IFN-gamma-induced STAT1 phosphorylation, whereas double knockdown of both PTPN2 and STAT1 protected beta-cells against cytokine-induced apoptosis, suggesting that STAT1 hyperactivation is responsible for the aggravation of cytokine-induced beta-cell death in PTPN2-deficient cells. CONCLUSIONS: We identified a functional role for the type 1 diabetes candidate gene PTPN2 in modulating IFN-gamma signal transduction at the beta-cell level. PTPN2 regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes

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

Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function

OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- to S-phase transition during the cycling of many cell types and is required for pancreatic beta-cell growth and function. However, the consequences of overexpression of E2F1 in beta-cells are unknown. RESEARCH DESIGN AND METHODS-The effects of E2F1 overexpression on beta-cell proliferation and function were analyzed in isolated rat beta-cells and in transgenic mice. RESULTS-Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta-cells 20-fold but also enhanced beta-cell death. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. CONCLUSIONS-Overexpression of E2F1, either in vitro or in vivo, can stimulate beta-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta-cells, making it a strategic target for therapeutic manipulation of beta-cell function. Diabetes 59:1435-1444, 201

JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells

Cytokines contribute to pancreatic β-cell apoptosis in type 1 diabetes (T1D) by modulation of β-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated β-cell dysfunction and death. The cytokines IL-1β+IFN-γ induced an early and transitory upregulation of JunB by NF-κB activation. Knockdown of JunB by RNA interference increased cytokine-mediated expression of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers, leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in purified rat primary β-cells. JunB knockdown β-cells and junB−/− fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished iNOS and ER markers expression and protected β-cells from cytokine-induced cell death. These findings demonstrate a novel and unexpected role for JunB as a regulator of defense mechanisms against cytokine- and ER stress-mediated apoptosis

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett’s esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett’s Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%–88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients

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

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