Factors associated with spatial clustering of foot-and-mouth disease in Nepal

The purpose of this study was to quantify associations between hypothesized epidemiological factors and the spatial distribution of foot-and-mouth disease (FMD) in Nepal. Spatial clustering of reports of at least one FMD case by Village Development Committee (VDC) in 2004 was examined by use of the spatial scan statistic. A Bayesian Poisson multivariate regression model was used to quantify the association between the number of reports and 25 factors hypothesized to be associated with FMD risk. The spatial scan statistic identified (P < 0.01) two clusters of FMD reports. Large numbers of people, buffalo, and animal technicians in a district were associated with an elevated risk of a VDC reporting ≥1 FMD case. The knowledge of high-risk areas and factors associated with the risk of FMD in Nepal could be applied in future disease control programs

Protein profiling and pseudo-parallel reaction monitoring to monitor a fusion-associated conformational change in hemagglutinin.

Influenza infection requires viral escape from early endosomes into the cytosol, which is enabled by an acid-induced irreversible conformational transformation in the viral protein hemagglutinin. Despite the direct relationship between this conformational change and infectivity, label-free methods for characterizing this and other protein conformational changes in biological mixtures are limited. While the chemical reactivity of the protein backbone and side-chain residues is a proxy for protein conformation, coupling this reactivity to quantitative mass spectrometry is a challenge in complex environments. Herein, we evaluate whether electrophilic amidination coupled with pseudo-parallel reaction monitoring is an effective label-free approach to detect the fusion-associated conformational transformation in recombinant hemagglutinin (rHA). We identified rHA peptides that are differentially amidinated between the pre- and post-fusion states, and validated that this difference relies upon the fusion-associated conformational switch. We further demonstrate that we can distinguish the fusion profile in a matrix of digested cellular lysate. This fusion assay can be used to evaluate fusion competence for modified HA. Graphical abstract

DNA Spools under Tension

DNA-spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core are ubiquitous in nature. We develop a general theory describing the non-equilibrium behavior of DNA-spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics

Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by Munc18c <i>In Vitro</i>

Background: Translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the plasma membrane is responsible for the increased rate of glucose transport into fat and muscle cells in response to insulin. This represents a specialised form of regulated membrane trafficking. Intracellular membrane traffic is subject to multiple levels of regulation by conserved families of proteins in all eukaryotic cells. Notably, all intracellular fusion events require SNARE proteins and Sec1p/Munc18 family members. Fusion of GLUT4-containing vesicles with the plasma membrane of insulin-sensitive cells involves the SM protein Munc18c, and is regulated by the formation of syntaxin 4/SNAP23/VAMP2 SNARE complexes. Methodology/Principal Findings Here we have used biochemical approaches to characterise the interaction(s) of Munc18c with its cognate SNARE proteins and to examine the role of Munc18c in regulating liposome fusion catalysed by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. We demonstrate that Munc18c makes contacts with both t- and v-SNARE proteins of this complex, and directly inhibits bilayer fusion mediated by the syntaxin 4/SNAP23/VAMP2 SNARE complex. Conclusion/Significance Our reductionist approach has enabled us to ascertain a direct inhibitory role for Munc18c in regulating membrane fusion mediated by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. It is important to note that two different SM proteins have recently been shown to stimulate liposome fusion mediated by their cognate SNARE complexes. Given the structural similarities between SM proteins, it seems unlikely that different members of this family perform opposing regulatory functions. Hence, our findings indicate that Munc18c requires a further level of regulation in order to stimulate SNARE-mediated membrane fusion

Fetal hyperglycemia and a high fat diet contribute to aberrant glucose tolerance and hematopoiesis in adulthood

Background Children exposed to gestational diabetes mellitus (GDM) during pregnancy are at increased risk of obesity, diabetes, and hypertension. Our goal was to identify metabolic and hematopoietic alterations after intrauterine exposure to maternal hyperglycemia that may contribute to the pathogenesis of chronic morbidities. Methods Streptozotocin treatment induced maternal hyperglycemia during the last third of gestation in rat dams. Offspring of control mothers (OCM) and diabetic mothers (ODM) were evaluated for weight, glucose tolerance, insulin tolerance, and hematopoiesis defects. The effects of aging were examined in normal and high fat diet (HFD)-fed young (8-week-old) and aged (11-month-old) OCM and ODM rats. Results Young adult ODM males on a normal diet, but not females, displayed improved glucose tolerance due to increased insulin levels. Aged ODM males and females gained more weight than OCM on a HFD and had worse glucose tolerance. Aged ODM males fed a HFD were also neutrophilic. Increases in bone marrow cellularity and myeloid progenitors preceded neutrophilia in ODM males fed a HFD. Conclusion When combined with other risk factors like HFD and aging, changes in glucose metabolism and hematopoiesis may contribute to the increased risk of obesity, type 2 diabetes, and hypertension observed in children of GDM mothers

Receiver Function Constraints on Crustal Seismic Velocities and Partial Melting beneath the Red Sea Rift and Adjacent Regions, Afar Depression

The Afar Depression is an ideal locale for the investigation of crustal processes involved in the transition from continental rifting to oceanic spreading. To provide relatively high resolution images of the crust beneath the Red Sea rift (RSR) represented by the Tendaho graben in the Afar Depression, we deployed an array of 18 broadband seismic stations in 2010 and 2011. Stacking of about 2300 receiver functions from the 18 and several nearby stations along the ~200 km long array reveals an average crustal thickness of 22 ± 4 km, ranging from ~17 km near the RSR axis to 30 km within the overlap zone between the Red Sea and Gulf of Aden rifts. The resulting anomalously high Vp/Vs ratios decrease from 2.40 in the southwest to 1.85 within the overlap zone. We utilize theoretical Vp and melt fraction relationships to obtain an overall highly reduced average crustal Vp of ~5.1 km/s. The melt percentage is about 10% beneath the RSR while the overlap zone contains minor quantities of partial melt. The observed high Vp/Vs values beneath most of the study area indicate widespread partial melting beneath the southwest half of the profile, probably as a result of gradual eastward migration of the RSR axis. Our results also suggest that the current extensional strain in the lower crust beneath the region is diffuse, while the strain field in the upper crust is localized along narrow volcanic segments. These disparate styles of deformation imply a high degree of decoupling between the upper and lower crust

Gamifying self-management of chronic illnesses: amixed-methods study

Background: Self-management of chronic illnesses is an ongoing issue in health care research. Gamification is a concept that arose in the field of computer science and has been borrowed by many other disciplines. It is perceived by many that gamification can improve the self-management experience of people with chronic illnesses. This paper discusses the validation of a framework (called The Wheel of Sukr) that was introduced to achieve this goal.Objective: This research aims to (1) discuss a gamification framework targeting the self-management of chronic illnesses and (2) validate the framework by diabetic patients, medical professionals, and game experts.Methods: A mixed-method approach was used to validate the framework. Expert interviews (N=8) were conducted in order to validate the themes of the framework. Additionally, diabetic participants completed a questionnaire (N=42) in order to measure their attitudes toward the themes of the framework.Results: The results provide a validation of the framework. This indicates that gamification might improve the self-management of chronic illnesses, such as diabetes. Namely, the eight themes in the Wheel of Sukr (fun, esteem, socializing, self-management, self-representation, motivation, growth, sustainability) were perceived positively by 71% (30/42) of the participants with P value &lt;.001.Conclusions: In this research, both the interviews and the questionnaire yielded positive results that validate the framework (The Wheel of Sukr). Generally, this study indicates an overall acceptance of the notion of gamification in the self-management of diabete

The MafA transcription factor becomes essential to islet β-cells soon after birth

The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB

Chemistry courses as the turning point for premedical students

Previous research has documented that negative experiences in chemistry courses are a major factor that discourages many students from continuing in premedical studies. This adverse impact affects women and students from under-represented minority (URM) groups disproportionately. To determine if chemistry courses have a similar effect at a large public university, we surveyed 1,036 students from three entering cohorts at the University of California, Berkeley. We surveyed students at the beginning of their first year at the university and again at the end of their second year. All subjects had indicated an interest in premedical studies at the time they entered the university. We conducted follow-up interviews with a stratified sub-set of 63 survey respondents to explore the factors that affected their level of interest in premedical studies. Using a 10-point scale, we found that the strength of interest in premedical studies declined for all racial/ethnic groups. In the follow-up interviews, students identified chemistry courses as the principal factor contributing to their reported loss of interest. URM students especially often stated that chemistry courses caused them to abandon their hopes of becoming a physician. Consistent with reports over more than 50 years, it appears that undergraduate courses in chemistry have the effect of discouraging otherwise qualified students, as reflected in their admission to one of the most highly selective public universities in the US, from continuing in premedical studies, especially in the case of URM students. Reassessment of this role for chemistry courses may be overdue