Distribution and Redistribution of HIV-1 Nucleocapsid Protein in Immature, Mature, and Integrase-Inhibited Virions: a Role for Integrase in Maturation

During virion maturation, HIV-1 capsid protein assembles into a conical core containing the viral ribonucleoprotein (vRNP) complex, thought to be composed mainly of the viral RNA and nucleocapsid protein (NC). After infection, the viral RNA is reverse transcribed into double-stranded DNA, which is then incorporated into host chromosomes by integrase (IN) catalysis. Certain IN mutations (class II) and antiviral drugs (allosteric IN inhibitors [ALLINIs]) adversely affect maturation, resulting in virions that contain “eccentric condensates,” electron-dense aggregates located outside seemingly empty capsids. Here we demonstrate that in addition to this mislocalization of electron density, a class II IN mutation and ALLINIs each increase the fraction of virions with malformed capsids (from ∼12% to ∼53%). Eccentric condensates have a high NC content, as demonstrated by “tomo-bubblegram” imaging, a novel labeling technique that exploits the susceptibility of NC to radiation damage. Tomo-bubblegrams also localized NC inside wild-type cores and lining the spherical Gag shell in immature virions. We conclude that eccentric condensates represent nonpackaged vRNPs and that either genetic or pharmacological inhibition of IN can impair vRNP incorporation into mature cores. Supplying IN in trans as part of a Vpr-IN fusion protein partially restored the formation of conical cores with internal electron density and the infectivity of a class II IN deletion mutant virus. Moreover, the ability of ALLINIs to induce eccentric condensate formation required both IN and viral RNA. Based on these observations, we propose a role for IN in initiating core morphogenesis and vRNP incorporation into the mature core during HIV-1 maturation

Eating Behavior, Physical Activity and Exercise Training: A Randomized Controlled Trial in Young Healthy Adults

Regular physical activity (PA) is an important part of the treatment of several medical conditions, including overweight and obesity, in which there may be a weakened appetite control. Eating behaviour traits influence weight control and may be different in active and sedentary subjects. This paper reports the relationships between the time spent in sedentary behaviour and physical activity (PA) of different intensity, and eating behaviour traits in young, healthy adults. Additionally, it reports the results of a six-month-long, randomized, controlled trial to examine the effect of an exercise intervention on eating behaviour traits. A total of 139 young (22.06 ± 2.26 years) healthy adults (68.35% women) with a Body Mass Index (BMI) of 24.95 ± 4.57 kg/m2 were enrolled. Baseline assessments of habitual PA were made using wrist-worn triaxial accelerometers; eating behaviour traits were examined via the self-reported questionnaires: Binge Eating, Three-Factor Eating Questionnaire-R18 and Control of Eating Questionnaire. The subjects were then randomly assigned to one of three groups: control (usual lifestyle), moderate-intensity exercise (aerobic and resistance training 3¨C4 days/week at a heart rate equivalent to 60% of the heart rate reserve (HRres) for the aerobic component, and at 50% of the 1 repetition maximum (RM) for the resistance component), or vigorous-intensity exercise (the same training but at 80% HRres for half of the aerobic training, and 70% RM for the resistance training). At baseline, sedentary behaviour was inversely associated with binge eating (r = −0.181, p < 0.05) and with uncontrolled eating (r = −0.286, p = 0.001). Moderate PA (MPA) was inversely associated with craving control (r = −0.188, p < 0.05). Moderate-to-vigorous PA (MVPA) was directly associated with binge eating (r = 0.302, p < 0.001) and uncontrolled eating (r = 0.346, p < 0.001), and inversely associated with craving control (r = −0.170, p < 0.015). Overall, PA was directly associated with binge eating (r = 0.275, p = 0.001), uncontrolled eating (r = 0.321, p < 0.001) and emotional eating (r = 0.204, p < 0.05). Additionally, only emotional eating was modified by the intervention, increasing in the vigorous-intensity exercise group (p < 0.05). In summary, we observed that time spent in sedentary behaviour/PA of different intensity is associated with eating behaviour traits, especially binge eating in young adults. In contrast, the six-month exercise intervention did not lead to appreciable changes in eating behaviour traits

Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

The decisions of Spanish youth : a cross-section study

The original publication is available at www.springerlink.comThis paper presents a simultaneous model for the joint decisions of working, studying and leaving the parental household by young people in Spain. Using cross-section data from the 1990–1991 Encuesta de Presupuestos Familiares, the model is estimated by a two stage estimation method. Endogeneity of the three decisions proves to be important in order to understand the dynamics of household formation. Our results also confirm a number of plausible intuitions about the effect of individual characteristics and economic variables on these decisions, and provide some new insights into the reasons for young people in Spain remaining in large numbers in the parental home. Most of the results are gender independent.Publicad

Water Solubilization Using Nonionic Surfactants from Renewable Sources in Microemulsion Systems

In this study the effect of temperature, NaCl and oils (hydrocarbons: C8–C16) on the formation and solubilization capacity of the systems of oil/monoacylglycerols (MAG):ethoxylated fatty alcohols (CEO20)/propylene glycol (PG)/water was investigated. The effects of the surfactant mixture on the phase behavior and the concentration of water or oil in the systems were studied at three temperatures (50, 55, 60 °C) and with varied NaCl solutions (0.5; 2; 11%). Electrical conductivity measurement, FTIR spectroscopy and the DSC method were applied to determine the structure and type of the microemulsions formed. The dimension of the microemulsion droplets was characterized by dynamic light scattering. It has been stated that the concentration of CEO20 has a strong influence on the shape and extent of the microemulsion areas. Addition of a nonionic surfactant to the mixture with MAG promotes an increase in the area of microemulsion formation in the phase diagrams, and these areas of isotropic region did not change considerably depending on the temperature, NaCl solution and oil type. It was found that, depending on the concentration of the surfactant mixture, it was possible to obtain U-type microemulsions with dispersed particles size distribution ranging from 25 to 50 nm and consisting of about 30–32% of the water phase in the systems. The conditions under which the microemulsion region was found (electrolyte and temperature—insensitive, comparatively low oil and surfactant concentration) could be highly useful in detergency

Is there an association between depressive and urinary symptoms during and after pregnancy?

Depressive symptoms and urinary symptoms are both highly prevalent in pregnancy. In the general population, an association is reported between urinary symptoms and depressive symptoms. The association of depressive and urinary symptoms has not yet been assessed in pregnancy. In this study, we assessed (1) the prevalence of depressive symptoms, over-active bladder (OAB) syndrome, urge urinary incontinence (UUI) and stress urinary incontinence (SUI) during and after pregnancy using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Urogenital Distress Inventory (UDI) and (2) the association of depressive symptoms with urinary incontinence and over-active bladder syndrome during and after pregnancy, controlling for confounding socioeconomic, psychosocial, behavioural and biomedical factors in a cohort of healthy nulliparous women. Our data show a significant increase in prevalence of depressive symptoms, UUI, SUI and OAB during pregnancy and a significant reduction in prevalence of depressive symptoms, SUI and OAB after childbirth. UUI prevalence did not significantly decrease after childbirth. In univariate analysis, urinary incontinence and the OAB syndrome were significantly associated with a CES-D score indicative of a possible clinical depression at 36 weeks gestation. However, after adjusting for possible confounding factors, only the OAB syndrome remained significantly associated (OR 4.4 [1.8–10.5]). No association was found between depressive and urinary symptoms at 1 year post-partum. Only OAB was independently associated with depressive symptoms during pregnancy. Possible explanations for this association are discussed

IL-10 overexpression predisposes to invasive aspergillosis by suppressing antifungal immunity

© 2017 American Academy of Allergy, Asthma & ImmunologyProinflammatory immune responses are critically required for antimicrobial host defenses; however, excessive inflammation has the potential to damage host tissues thereby paradoxically contributing to the progression of infection. A central negative regulator of inflammatory responses is IL-10, an immunosuppressive cytokine with a wide variety of functions across multiple cell types. Although the role of IL-10 during infection appears to vary for different microorganisms, a largely detrimental role has been attributed to this cytokine during fungal disease. Given the variable risk of infection and its outcome among patients with comparable predisposing factors, susceptibility to invasive aspergillosis (IA) is thought to rely largely on genetic predisposition. The initial investigation of genetic variability at the IL10 locus led to the identification of single nucleotide polymorphisms (SNPs) influencing its transcriptional activity; thus, IL-10 may be a reasonable candidate for the genetic regulation of susceptibility to IA in high-risk patients.Supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/2014 to A.C., IF/01390/2014 to E.T., IF/00021/2014 to R.S., and SFRH/BPD/96176/2013 to C.C.), the Conselho de Reitores das Universidades Portuguesas (CRUP), Portugal (Ações Integradas Luso-Alemãs A-43/16), the Deutscher Akademischer Austauschdienst (DAAD) (project-ID 57212690), the Fondo de Investigaciones Sanitarias (Madrid, Spain) (grant #PI12/02688) and the ERA-NET PathoGenoMics (grant #0315900A).info:eu-repo/semantics/publishedVersio