Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Insulin Action in the Brain Clinically Relevant?

Last year marked the ninetieth anniversary of the discovery of insulin by Nobel Laureates Frederick Banting and John Macleod, as well as Charles Best and James Bertram Collip. The initial success of insulin’s ability to lower glucose levels in type 1 diabetes is now shadowed by the urgent need to characterize insulin resistance and secretion defects in type 2 diabetes and obesity. Insulin triggers signaling pathways in liver, muscle, and fat that inhibit glucose production and increase glucose uptake (1). However, it has only been in recent years that the brain has received attention for being an insulin-sensitive organ that regulates food intake (2) and glucose (3) and lipid (4) homeostasis in animals (Fig. 1). FIG. 1. A working hypothesis for insulin action in the brain. Insulin triggers signaling cascades in the brain to regulate food intake and modulate the reward-related hedonic food response. In addition, brain insulin action alters glucose and lipid metabolism. The hypothalamus (blue) is the main effector of the metabolic changes induced by insulin and can coordinate the prefrontal cortex (green) to regulate the hedonic assessment of appetite. WAT, white adipose tissue. Circulating insulin crosses the blood-brain barrier and acts on its receptor in the hypothalamus to lower food intake and body weight (2). Infusion of insulin into the central nervous system (CNS) lowers food intake in rats (5), mice (6), and baboons (7), whereas hyperphagia is detected in neuronal insulin receptor knockout mice (8). Further, high-fat feeding induces hypothalamic insulin resistance in rodents (9). Although these animal studies expand the role of insulin to regulate appetite and suggest that characterizing insulin signaling pathways may reveal novel targets that reverse brain insulin resistance in obesity, a central question remains, Is …
Probabilistic Head-Driven Parsing for Discourse Structure

We describe a data-driven approach to building interpretable discourse structures for appointment scheduling dialogues. We represent discourse structures as headed trees and model them with probabilistic head-driven parsing techniques. We show that dialogue-based features regarding turn-taking and domain specific goals have a large positive impact on performance. Our best model achieves an f-score of 43.2% for labelled discourse relations and 67.9% for unlabelled ones, significantly beating a right-branching baseline that uses the most frequent relations.
Odour Maps in the Brain of Butterflies with Divergent Host-Plant Preferences

Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.
Effects of Cysteine to Serine Substitutions in the Two Inter-Chain Disulfide Bonds of Insulin

Abstract Using sitedirected mutagenesis we deleted the two interchain disulfide bonds of insulin, separately or both, by substitution of the cysteine residues with serine. Deletion of A20-B19 or both of the two interchain disulfide bonds resulted in the complete loss of secretion of the mutant singlechain porcine insulin precursor (PIP) from Saccharomyces cerevisiae cells. Removal of the A7-B7 disulfide bond resulted in a large reduction of secretion, but we could obtain the mutant for analysis of its biological and some physico chemical properties. The A7-B7 disulfide bond deleted insulin mutant retained only 0.1% receptorbinding activity compared with porcine insulin, and its in vivo biological potency measured by mouse convulsion assay was also very low. We also studied some physicochemical properties of the mutant using circular dichroism, native polyacrylamide gel electrophoresis and reversedphase HPLC, which revealed some structural changes of the mutant peptides compared to native insulin. The present study shows that the two interchain disulfide bonds are important for efficient in vivo folding/secretion of PIP from yeast, especially the A20-B19 disulfide bond, and that the A7-B7 disulfide bond is crucial for maintaining the native conformation and biological activity of insulin.
Duration or disadvantage? Exploring nativity, ethnicity, and health in midlife.

OBJECTIVES This study examined nativity as a risk factor for poor physical and emotional health for an ethnically diverse population making the transition into retirement. The authors addressed whether the health disadvantage observed for immigrants lessens with increased time spent in the country (supporting theories of assimilation) or increases with duration of residence (supporting theories of cumulative disadvantage). METHODS The sample was drawn from Waves 1 and 2 of the Health and Retirement Study (HRS), an in-depth economic, social, and health database of persons in midlife and beyond. The analyses were restricted to 9,912 native-born and 1,031 foreign-born individuals. RESULTS The data revealed that after socioeconomic factors were controlled, foreign-born individuals were at higher risk of poor emotional health than their native-born counterparts. Although aging immigrants displayed worse health than the native-born population, this disadvantage was mediated by duration of residence (young age at migration) and socioeconomic incorporation. DISCUSSION These findings extend our understanding of nativity and duration as risk factors for poor physical and emotional health. Immigrants may overcome the nativity disadvantages found for emotional distress with increased duration of residence, but the pattern becomes more complicated with the inclusion of race and Hispanic ethnicity.
Europa's surface color suggests an ocean rich with sodium chloride

The composition of Europa's surface may be representative of the subsurface ocean; however, considerable debate persists regarding the endogenous or exogenous nature of a hydrated sulfate feature on Europa. Direct evidence of oceanic salts on Europa's surface has been largely inconclusive. We show that the observed color within geologically young features on Europa's surface can be explained by sodium chloride delivered from the ocean below. We find that sodium chloride, when exposed to Europa surface conditions, accumulates electrons in F and M centers, yielding a yellow‐brown discoloration comparable to Europa's surface. Irradiation of sodium chloride from Europa's ocean thus provides a simple and elegant solution to the color of the non‐ice material observed on Europa. This evidence for endogenous salts suggests that Europa's ocean is interacting with a silicate seafloor, a critical consideration for assessing habitability.
Predictors of Peer Victimization in Peruvian Adolescents

Background: While bullying is recognized as a major public health concern worldwide, little research has been conducted on prevalence and predictors of bullying in Latin American countries such as Peru. Considering the negative effects that may be experienced by bully victims, including poor academic performance, psychological distress and in extreme cases suicide, identifying the factors associated with peer victimization is important to effectively addressing peer bullying. The purpose of this study was to estimate the prevalence of peer victimization in a sample of high school students in Cusco, Peru and to explore the relationship between victimization and potential correlating factors. Methods: A cross-sectional study of 949 high school aged adolescents from Cusco, Peru was undertaken. Adolescents from Cusco high schools were recruited and required to obtain parental consent to participate. The final sample of students completed a survey to answer questions about demographics, bullying, their parents’ parenting behaviors, the status of their home internet connection, and academic performance. Chi-square tests and adjusted logistic regression analysis were calculated using Stata version 12.1 and were used to assess potential risk factors associated with being bullied among boys and girls. Results: Over 20% of the sample reported being mistreated or bullied by peers. More boys than girls reported being bullied (28.5% vs. 19.5%; p = 0.002). Girls whose parents engaged in more positive parenting behaviors were less likely to be bullied, while having a home Internet connection and spending more than 60 minutes on social media during the previous day were associated with an increased risk of being bullied. Among boys, no variables were significantly associated with being bullied. Conclusions: Health practitioners may want to design bullying interventions that differ for boys and girls. Interventions for girls could benefit from increased parental involvement in particular. The association between time spent on social media and bullying among girls could also be investigated. Further research is needed to understand predictors of being bullied among males in this region.
The effect of performance-based financing on maternal healthcare use in Burundi: a two-wave pooled cross-sectional analysis

ABSTRACT Background: Several developing countries, especially in Africa, have implemented performance-based financing (PBF) schemes with the aim of improving healthcare provision. PBF was first implemented in Burundi in 2006 as a pilot programme in three provinces and was rolled out nationwide in 2010. Objective: To enrich existing studies on Burundi in three ways. Firstly, by evaluating the effect of PBF on maternal care at primary and hospital levels; secondly, on the possession of maternity logbooks for maternal care records; and thirdly, how the amount of subsidies influences healthcare outputs. Design: We used data from repeated cross-sectional surveys in 500 households (intervention group: 225; control group: 275) conducted in 2006 and 2008. A total of 274 women, aged 15–49, who had recently given birth, were interviewed about the use of maternal healthcare and the possession of maternity logbooks. We performed a difference-in-differences analysis using pooled cross-sectional survey data from 2006 and 2008. Results: We found that PBF is associated with an increased institutional deliveries probability of 39.5 percentage points (p < 0.01) – a relative improvement of 81.8%. Institutional deliveries probability increased significantly only at health centre level by 33.6 percentage points (p < 0.01), a relative rise of 80.6%. There is an indication of a positive spillover effect of PBF on the possession of maternity logbooks. We found no PBF effect on the number of antenatal care visits and anti-tetanus immunization. Conclusions: Our findings suggest that institutional delivery highly improved because it came from a low baseline and its unit payment was relatively high, leading health workers to promote its use. The fact that deliveries mainly increased in health centres and not in hospitals may be explained by the context of how health delivery is organized in Burundi. Health policymakers have to determine the appropriate financial incentives that best influence the improvement of each health service.
Allogeneic transplant for chronic myeloid leukemia in 2010

Tyrosine kinase inhibitor (TKI) therapy has revolutionized the therapy of chronic myeloid leukemia (CML). Thus, while in the near past allogeneic transplantation was the curative option for CML, imatinib, nilotinib, and dasatinib have pushed transplantation to the role of salvage therapy in CML. Still, TKI therapy still fails some patients, and so the clinical challenge is to integrate transplantation in a safe and sane manner. This manuscript reviews the data on the variables that have an influence on outcome following transplantation, and discusses the variables to consider in determining who and when patients should receive transplantation.
Enhanced Recovery in Thoracic Surgery: A Review

The main goal of enhanced recovery program after thoracic surgery is to minimize stress response, reduce postoperative pulmonary complications, and improve patient outcome, which will in addition decrease hospital stay and reduce hospital costs. As minimally invasive technique, video-assisted thoracoscopic surgery represents an important element of enhanced recovery program in thoracic surgery. Anesthetic management during preoperative, intraoperative and postoperative period is essential for the enhanced recovery. In the era of enhanced recovery protocols, non-intubated thoracoscopic procedures present a step forward. This article focuses on the key elements of the enhanced recovery program in thoracic surgery. Having reviewed recent literature, the authors highlight potential procedures and techniques that might be incorporated into the program.
Preliminary assessment of a school-based healthy lifestyle intervention among rural elementary school children.

BACKGROUND Childhood obesity has become a national public health crisis in America. Physical inactivity and unhealthy eating behaviors may contribute to the childhood obesity epidemic. School-based healthy lifestyle interventions play a promising role in preventing and controlling childhood obesity. A comprehensive school-based healthy lifestyle intervention was implemented in 4 rural elementary schools in Kentucky. METHODS The intervention included 4 goals: improving physical education, health education, family/community involvement, and school wellness policies. Children's physical activity was assessed by pedometer, and nutrition was assessed by a previous day recall survey in January (baseline), February (t1), March (t2), April (t3), and May (t4) of 2011. RESULTS The intervention had significant effects on increasing the percentages of children meeting physical activity (1% vs 5%, p < .01) and nutrition (15% vs 26%, p < .01) recommendations. The effects of the intervention on physical activity and nutrition depended on school, grade, and age of the children. There was an increasing linear trend of physical activity and an increasing quadratic trend of nutrition over time among children. CONCLUSIONS The intervention had beneficial effects in improving healthy behaviors among children. Further studies are needed to assess its long-term effects and cost-effectiveness.
Body-hypomethylated human genes harbor extensive intragenic transcriptional activity and are prone to cancer-associated dysregulation

Abstract Genomic DNA methylation maps (methylomes) encode genetic and environmental effects as stable chemical modifications of DNA. Variations in DNA methylation, especially in regulatory regions such as promoters and enhancers, are known to affect numerous downstream processes. In contrast, most transcription units (gene bodies) in the human genome are thought to be heavily methylated. However, epigenetic reprogramming in cancer often involves gene body hypomethylation with consequences on gene expression. In this study, we focus on the relatively unexplored phenomenon that some gene bodies are devoid of DNA methylation under normal conditions. Utilizing nucleotide-resolution methylomes of diverse samples, we show that nearly 2000 human genes are commonly hypomethylated. Remarkably, these genes occupy highly specialized genomic, epigenomic, evolutionary and functional niches in our genomes. For example, hypomethylated genes tend to be short yet encode significantly more transcripts than expected based upon their lengths, include many genes involved in nucleosome and chromatin formation, and are extensively and significantly enriched for histone-tail modifications and transcription factor binding with particular relevance for cis-regulation. Furthermore, they are significantly more prone to cancer-associated hypomethylation and mutation. Consequently, gene body hypomethylation represents an additional layer of epigenetic regulatory complexity, with implications on cancer-associated epigenetic reprogramming.
A new model of work role performance: Positive behavior in uncertain and interdependent contexts

We propose that interdependence in a work context determines to what extent work roles are embedded within a broader social system and, further, that uncertainty determines whether work roles can be formalized or whether they emerge through adaptive and proactive behavior. Cross-classification of task, team member, and organization member behaviors with proficiency, adaptivity, and proactivity produced nine subdimensions of work role performance. Ratings from 491 supervisors from 32 organizations and self-ratings from employees in two organizations (n's = 1,228 and 927) supported the proposed distinctions. Self-reports of proactivity were positively correlated with two external measures of proactivity.
Difference in Celiac Disease Risk Between Swedish Birth Cohorts Suggests an Opportunity for Primary Prevention

OBJECTIVES. Sweden experienced a unique epidemic of celiac disease in children <2 years of age. The epidemic was partly explained by changes in infant feeding over time and indicated a multifactorial pathogenesis. The main aim of this study was to analyze celiac disease risk in epidemic and postepidemic birth cohorts up to preschool age, to explore further the opportunity for primary prevention. METHODS. A population-based incidence register of celiac disease in children covering the entire nation from 1998 to 2003 and part of the country back to 1973 was analyzed. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria for celiac disease were used. The annual incidence rate for each age group and the cumulative incidence according to age for each birth cohort were calculated. RESULTS. A considerable difference in cumulative incidences of celiac disease at comparable ages was demonstrated between birth cohorts from the epidemic and postepidemic periods. The difference persisted during the preschool years, although it decreased somewhat with age. During the last years of the follow-up period, there was again a successive increase in incidence rate among children <2 years of age. CONCLUSIONS. The difference in celiac disease risk between birth cohorts at comparable ages suggests an opportunity for primary prevention. This highlights the importance of further exploring the role of infant feeding and exogenous factors besides dietary gluten that might initiate or prevent disease development. Moreover, on the basis of postepidemic incidence trends, we speculate that the Swedish epidemic might not have been as unique as thought previously, although its magnitude was striking.
Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans

Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
The causes of epistasis

Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions—called epistasis—have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype–phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability.