Affiliation in the social interactions in captivity of the torch tail rat, Trinomys yonenagae (Rodentia: Echimyidae)

In a previous paper, we measured the affiliation between male individuals of Trinomys yonenagae and concluded that the intensity of affiliation was high and did not differ between animals from the same social group and from different social groups. In this paper, we report the results obtained with the same experimental procedure with female individuals. We also discuss sexual differences in the social interaction of this species. The experimental procedure was based on 40-min encounters between residents, which remained alone in an arena for 24 h, and introduced intruders, in a round-robin design. We quantified one variable indicative of activity level (number of squares crossed), one indicative of anxiety (time in marginal squares), three indicative of affiliation (number of physical contacts, mean distance between rodents, and total duration of physical contact), and the number of sound emissions. No aggressive behaviors were exhibited. The results indicate that there is a high level of affiliation mediated by acoustic communication both for males and females and that no anxiety is associated with social context, especially in females. The evolution of sociality in T. yonenagae was probably linked to an increase of tolerance especially among adult females. We also suggest that predation was a stronger selective pressure than resource availability in the evolution of sociality in this species.     

FALSE ANEURYSM OF THE LEFT VENTRICLE: CASE REPORT WITH PRE- AND POSTOPERATIVE EVALUATION

A 66-year-old woman developed chronic congestive heart failure after myocardial infarction of the anterior wall of the left ventricle. Angiographic studies revealed total proximal occlusion of the left anterior descending coronary artery and a large saccular aneurysm located on the anteroapical aspect of the left ventricle. Resection of a false aneurysm at operation resulted in improved cardiac function, and the patient made an uneventful recovery. Repeat evaluation six months later confirmed normal cardiac hemodynamics and left ventricular angiographic characteristics. To our knowledge, this is the first documented case of normalized heart function resulting from resection of a false aneurysm of the left ventricle. Functional classification according to the New York Heart Association improved dramatically, rising from Class IV preoperatively to Class I after operation.     

Cross-Sectional and Prospective Associations between Physical Activity and C-Reactive Protein in Males

BackgroundThere is conflicting evidence about the association between physical activity and inflammatory markers. Few prospective studies are available, particularly from low and middle-income countries. This study was aimed at assessing the cross-sectional and prospective associations between physical activity and C-reactive protein (CRP) levels in males belonging to the 1982 Pelotas (Brazil) Birth Cohort Study.MethodsThe sample comprised 2,213 males followed up at the ages of 18 and 23 years. We performed high sensitivity CRP assays; we used a cut-off of 3 mg/L in categorical analyses. We measured physical activity by self-report at ages 18 and 23 years. Body mass index and waist circumference were studies as possible mediators.ResultsCRP levels above the 3mg/L cut-off were found in 13.3% (95%CI: 11.7; 14.8) of the individuals. We found no evidence for an association between physical activity (leisure-time or all-domains) and either continuous (geometrical mean) or categorical CRP. We confirmed these null findings in (a) prospective and cross-sectional analyses; (b) trajectories analyses.ConclusionsThere was no association between CRP levels and physical activity levels in early adulthood in a large birth cohort. Little variability in CRP at this early age is the likely explanation for these null findings.     

Genomic Ancestry,Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

Background

Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification.

Materials/Methods

We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality.

Results

European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups.

Conclusions

Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.     

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug class.     

Poly(ADP-ribose) polymerases in double-strand break repair: Focus on PARP1, PARP2 and PARP3

Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins catalysed by Poly(ADP-ribose) polymerases (PARP). A wealth of recent advances in the biochemical and functional characterization of the DNA-dependent PARP family members have highlighted their key contribution in the DNA damage response network, the best characterized being the role of PARP1 and PARP2 in the resolution of single-strand breaks as part of the BER/SSBR process. How PARylation contributes to the repair of double-strand breaks is less well defined but has become recently the subject of significant research in the field. The aim of this review is to provide an overview of the current knowledge concerning the role of the DNA-activated PARP1, PARP2 and PARP3 in cellular response to double-strand breaks (DSB). In addition, we outline the biological significance of these properties in response to programmed DNA lesions formed during physiological processes such as antibody repertoire assembly and diversification.     

Production of a Plant-Derived Immunogenic Protein Targeting ApoB100 and CETP: Toward a Plant-Based Atherosclerosis Vaccine

In an effort to initiate the development of a plant-based vaccination model against atherosclerosis, a cholera toxin B subunit (CTB)-based chimeric protein was designed to target both ApoB100 and CETP epitopes associated with immunotherapeutic effects in atherosclerosis. Epitopes were fused at the C-terminus of CTB to yield a protein called CTB:p210:CETPe. A synthetic gene coding for CTB:p210:CETPe was successfully transferred to tobacco plants with no phenotypic alterations. Plant-derived CTB:p210:CETPe was expressed and assembled in the pentameric form. This protein retained the target antigenic determinants, as revealed by GM1-ELISA and Western blot analyses. Higher expresser lines reached recombinant protein accumulation levels up to 10 µg/g fresh weight in leaf tissues and these lines carry a single insertion of the transgene as determined by qPCR. Moreover, when subcutaneously administered, the biomass from these CTB:p210:CETPe-producing plants was able to elicit humoral responses in mice against both ApoB100 and CETP epitopes and human serum proteins. These findings evidenced for the first time that atherosclerosis-related epitopes can be expressed in plants retaining immunogenicity, which opens a new path in the molecular farming field for the development of vaccines against atherosclerosis.     

Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide.