Transitions/relaxations in polyester adhesive/PET system

The correlations between the transitions and the dielectric relaxation processes of the oriented poly(ethylene terephthalate) (PET) pre-impregnated of the polyester thermoplastic adhesive have been investigated by differential scanning calorimetry (DSC) and dynamic dielectric spectroscopy (DDS). The thermoplastic polyester adhesive and the oriented PET films have been studied as reference samples. This study evidences that the adhesive chain segments is responsible for the physical structure evolution in the PET-oriented film. The transitions and dielectric relaxation modes’ evolutions in the glass transition region appear characteristic of the interphase between adhesive and PET film, which is discussed in terms of molecular mobility. The storage at room temperature of the adhesive tape involves the heterogeneity of the physical structure, characterized by glass transition dissociation. Thus, the correlation between the transitions and the dielectric relaxation processes evidences a segregation of the amorphous phases. Therefore, the physical structure and the properties of the material have been linked to the chemical characteristics

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug and evidence of drug resistance. Drug resistance has a genetic basis. In this study, genetic changes in β-tubulin, a gene associated with ivermectin resistance in nematodes, were seen in parasites obtained from the patients exposed to repeated ivermectin treatment compared with parasites obtained from the same patients before any exposure to ivermectin. Furthermore, the extent of the genetic changes was dependent on the level of ivermectin treatment exposure. This genetic selection was associated with a lower reproductive rate in the female parasites. The data indicates that this genetic selection is for a population of O. volvulus that is more tolerant to ivermectin. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. Monitoring for the possible development and spread of ivermectin resistance, as part of the control programmes, should be implemented so that any foci of resistant parasites can be treated by alternative control measures

Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation.

The Melanocortin-4 Receptor (MC4R) plays a pivotal role in energy homeostasis. We used human MC4R mutations associated with an increased or decreased risk of obesity to dissect mechanisms that regulate MC4R function. Most obesity-associated mutations impair trafficking to the plasma membrane (PM), whereas obesity-protecting mutations either accelerate recycling to the PM or decrease internalization, resulting in enhanced signaling. MC4R mutations that do not affect canonical Gαs protein-mediated signaling, previously considered to be non-pathogenic, nonetheless disrupt agonist-induced internalization, β-arrestin recruitment, and/or coupling to Gαs, establishing their causal role in severe obesity. Structural mapping reveals ligand-accessible sites by which MC4R couples to effectors and residues involved in the homodimerization of MC4R, which is disrupted by multiple obesity-associated mutations. Human genetic studies reveal that endocytosis, intracellular trafficking, and homodimerization regulate MC4R function to a level that is physiologically relevant, supporting the development of chaperones, agonists, and allosteric modulators of MC4R for weight loss therapy

Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation.

The Melanocortin-4 Receptor (MC4R) plays a pivotal role in energy homeostasis. We used human MC4R mutations associated with an increased or decreased risk of obesity to dissect mechanisms that regulate MC4R function. Most obesity-associated mutations impair trafficking to the plasma membrane (PM), whereas obesity-protecting mutations either accelerate recycling to the PM or decrease internalization, resulting in enhanced signaling. MC4R mutations that do not affect canonical Gαs protein-mediated signaling, previously considered to be non-pathogenic, nonetheless disrupt agonist-induced internalization, β-arrestin recruitment, and/or coupling to Gαs, establishing their causal role in severe obesity. Structural mapping reveals ligand-accessible sites by which MC4R couples to effectors and residues involved in the homodimerization of MC4R, which is disrupted by multiple obesity-associated mutations. Human genetic studies reveal that endocytosis, intracellular trafficking, and homodimerization regulate MC4R function to a level that is physiologically relevant, supporting the development of chaperones, agonists, and allosteric modulators of MC4R for weight loss therapy

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

High Level of Soluble HLA-G in the Female Genital Tract of Beninese Commercial Sex Workers Is Associated with HIV-1 Infection

Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009) and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008), and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P = 0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P = 0.03).This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis

The C-Terminus of Toxoplasma RON2 Provides the Crucial Link between AMA1 and the Host-Associated Invasion Complex

Host cell invasion by apicomplexan parasites requires formation of the moving junction (MJ), a ring-like apposition between the parasite and host plasma membranes that the parasite migrates through during entry. The Toxoplasma MJ is a secreted complex including TgAMA1, a transmembrane protein on the parasite surface, and a complex of rhoptry neck proteins (TgRON2/4/5/8) described as host cell-associated. How these proteins connect the parasite and host cell has not previously been described. Here we show that TgRON2 localizes to the MJ and that two short segments flanking a hydrophobic stretch near its C-terminus (D3 and D4) independently associate with the ectodomain of TgAMA1. Pre-incubation of parasites with D3 (fused to glutathione S-transferase) dramatically reduces invasion but does not prevent injection of rhoptry bulb proteins. Hence, the entire C-terminal region of TgRON2 forms the crucial bridge between TgAMA1 and the rest of the MJ complex but this association is not required for rhoptry protein injection