Mexican Trypanosoma cruzi T. cruzi I Strains with Different Degrees of Virulence Induce Diverse Humoral and Cellular Immune Responses in a Murine Experimental Infection Model

It is has been shown that the majority of T. cruzi strains isolated from Mexico belong to the T. cruzi I (TCI). The immune response produced in response to Mexican T. cruzi I strains has not been well characterized. In this study, two Mexican T. cruzi I strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro)(Qro) strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa) strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNγ, RANTES, MIG, MIP-1β, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice

Levels and patterns of objectively assessed physical activity and compliance with different public health guidelines in university students

ArticleBackground Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.Fundación para la Investigación SanitariaMinistry of Health and Consumer AffairsInstituto de Salud Carlos IIIRed de Investigación en Actividades Preventivas y de Promoción de Salu

Prevalence and trends of thinness, overweight and obesity among children and adolescents aged 3-18 years across Europe: a protocol for a systematic review and meta-analysis

Introduction Increasing prevalence of both thinness and excess weight during childhood and adolescence is a significant public health issue because of short-term health consequences and long-term tracking of weight status. Monitoring weight status in Europe may serve to identify countries and regions where rates of these disorders are either slowing down or increasing to evaluate recent policies aimed at appropriate body weight, and to direct future interventions. This study protocol provides a standardised and transparent methodology to improve estimating trends of thinness, overweight and obesity in children aged 3-18 years and adolescents across the European region between 2000 and 2017. Methods and analysis This protocol is guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and the Cochrane Collaboration Handbook. To identify relevant studies, a search will be conducted in MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science databases. From the selected studies, relevant references will be screened as supplemental sources. Finally, open search in websites from health institutions will be conducted to identify weight status data not published in scientific journals. Cross-sectional, follow-up studies and panel surveys reporting weight status (objectively measured height and weight) according to the International Obesity Task Force criteria, and written in English or Spanish will be included. Subgroup analyses will be carried out by gender, age, study year and country or European region. Discussion This study will provide a comprehensive description of weight status of children and adolescents across Europe from 2000 to 2017. The results will be disseminated in a peer-reviewed journal. This study will use data exclusively from published research or institutional literature, so institutional ethical approval is not required

Agreement between dual-energy X-ray absorptiometry and quantitative ultrasound to evaluate bone health in adolescents: The PRO-BONE study

Purpose: The present study aims to investigate the association between dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) parameters and the intermethods agreement in active males. Methods: In this cross-sectional study, bone health (by DXA and calcaneal QUS), physical activity (by accelerometers), and anthropometrics measurements were assessed in 117 active adolescents (12–14 y old). Bivariate correlation coefficients were calculated to assess the relationships between DXA standard regions of interest and QUS parameters. Intraclass correlation coefficients and Bland–Altman plots were used to assess the level of agreement between bone mineral content regions derived from DXA and stiffness index. The measurements were z score transformed for comparison. Results: Most QUS parameters were positive and significantly correlated with DXA outcomes (stiffness index: r = .43–.52; broadband ultrasound attenuation: r = .50–.58; speed of sound: r = .25–.27) with the hip showing the highest correlations. Moreover, the present study found fair to good intraclass correlation coefficients of agreement (.60–.68) between DXA and QUS to assess bone health. The Bland–Altman analysis showed a limited percentage of outliers (3.2%–8.6%). Conclusion: QUS device could represent an acceptable alternative method to assess bone health in active adolescent males

Optimizing the Parameters Governing the Fragmentation of Cross-Linked Peptides in a Tribrid Mass Spectrometer

We compared the five different ways of fragmentation available on a tribrid mass spectrometer and optimized their collision energies with regard to optimal sequence coverage of cross-linked peptides. We created a library of bis­(sulfosuccinimidyl)­suberate (BS3/DSS) cross-linked precursors, derived from the tryptic digests of three model proteins (Human Serum Albumin, creatine kinase, and myoglobin). This enabled in-depth targeted analysis of the fragmentation behavior of 1065 cross-linked precursors using the five fragmentation techniques: collision-induced dissociation (CID), beam-type CID (HCD), electron-transfer dissociation (ETD), and the combinations ETciD and EThcD. EThcD gave the best sequence coverage for cross-linked <i>m</i>/<i>z</i> species with high charge density, while HCD was optimal for all others. We tested the resulting data-dependent decision tree against collision energy-optimized single methods on two samples of differing complexity (a mix of eight proteins and a highly complex ribosomal cellular fraction). For the high complexity sample the decision tree gave the highest number of identified cross-linked peptide pairs passing a 5% false discovery rate (on average ∼21% more than the second best, HCD). For the medium complexity sample, the higher speed of HCD proved decisive. Currently, acquisition speed plays an important role in allowing the detection of cross-linked peptides against the background of linear peptides. Enrichment of cross-linked peptides will reduce this role and favor methods that provide spectra of higher quality. Data are available via ProteomeXchange with identifier PXD006131

Elastic electron scattering from 3-hydroxytetrahydrofuran: experimental and theoretical studies

We report the results of measurements and calculations for elastic electron scattering from 3-hydroxytetrahydrofuran (C4H8O2). The measurements are performed with a crossed electron-target beam apparatus and the absolute cross-sections are determined using the relative flow technique. The calculations are carried out using the Schwinger multichannel method in the static-exchange plus polarization (SEP) approximation. A set of angular differential cross-sections (DCS) is provided at five incident energies (6.5, 8, 10, 15 and 20 eV) over an angular range of 20–130°, and the energy dependence of the elastic DCS at a scattering angle of 120° is also presented. Integral elastic and elastic momentum transfer cross-sections have also been derived and calculated. The results are compared with those of recent measurements and calculations for the structurally similar molecule tetrahydrofuran (C4H8O)

Agreement Between Standard Body Composition Methods to Estimate Percentage of Body Fat in Young Male Athletes.

This is author's accepted manuscript.Final version available from Human Kinetics via the DOI in this record.PURPOSE: To examine the intermethods agreement of dual-energy X-ray absorptiometry (DXA) and foot-to-foot bioelectrical impedance analysis (BIA) to assess the percentage of body fat (%BF) in young male athletes using air-displacement plethysmography (ADP) as the reference method. METHODS: Standard measurement protocols were carried out in 104 athletes (40 swimmers, 37 footballers, and 27 cyclists, aged 12-14 y). RESULTS: Age-adjusted %BF ADP and %BF BIA were significantly higher in swimmers than footballers. ADP correlates better with DXA than with BIA (r = .84 vs r = .60, P < .001). %BF was lower when measured by DXA and BIA than ADP (P < .001), and the bias was higher when comparing ADP versus BIA than ADP versus DXA. The intraclass correlation coefficients between DXA and ADP showed a good to excellent agreement (r = .67-.79), though it was poor when BIA was compared with ADP (r = .26-.49). The ranges of agreement were wider when comparing BIA with ADP than DXA with ADP. CONCLUSION: DXA and BIA seem to underestimate %BF in young male athletes compared with ADP. Furthermore, the bias significantly increases with %BF in the BIA measurements. At the individual level, BIA and DXA do not seem to predict %BF precisely compared with ADP in young athletic populations.This work was done as part of the PRO-BONE study. It has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PCIG13-GA-2013-618496. M.V.N-F. received a PhD Student Internships Abroad scholarship from the National Council for Scientific and Technological Development (CNPq; process: 200340/2015-8) and a Brazilian PhD Student scholarship from the São Paulo Research Foundation (FAPESP; process. 2016/18436-8 and 2017/11732-3). E.U-G. received a PhD scholarship from Universidad de Castilla-La Mancha (2014/10340). A.C.F.M. received a postdoctoral scholarship from the São Paulo Research Foundation (FAPESP; process: 2014/13367-2 and 2015/14319-4)

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention