C-terminal amino acids are essential for human heat shock protein 70 dimerization

The human inducible heat shock protein 70 (hHsp70), which is involved in several major pathologies, including neurodegenerative disorders and cancer, is a key molecular chaperone and contributes to the proper protein folding and maintenance of a large number of protein structures. Despite its role in disease, the current structural knowledge of hHsp70 is almost exclusively based on its Escherichia coli homolog, DnaK, even though these two proteins only share ~50 % amino acid identity. For the first time, we describe a complete heterologous production and purification strategy that allowed us to obtain a large amount of soluble, full-length, and non-tagged hHsp70. The protein displayed both an ATPase and a refolding activity when combined to the human Hsp40. Multi-angle light scattering and bio-layer interferometry analyses demonstrated the ability of hHsp70 to homodimerize. The role of the C-terminal part of hHsp70 was identified and confirmed by a study of a truncated version of hHsp70 that could neither dimerize nor present refolding activity.

Electronic supplementary material

The online version of this article (doi:10.1007/s12192-014-0526-3) contains supplementary material, which is available to authorized users.     

PEM Anchorage on Titanium Using Catechol Grafting

Background

This study deals with the anchorage of polyelectrolyte films onto titanium surfaces via a cathecol-based linker for biomedical applications.

Methodology

The following study uses a molecule functionalized with a catechol and a carboxylic acid: 3-(3,4-dihydroxyphenyl)propanoic acid. This molecule is anchored to the TiO₂ substrate via the catechol while the carboxylic acid reacts with polymers bearing amine groups. By providing a film anchorage of chemisorption type, it makes possible to deposit polyelectrolytes on the surface of titanium.

Principal Findings

Infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), contact angle and atomic force microscopy (AFM) measurements show that the different steps of grafting have been successfully performed.

Conclusions

This method based on catechol anchorage of polyelectrolytes open a window towards large possibilities of clinical applications.     

Metapopulation patterns of additive and nonadditive genetic variance in the sea bass (Dicentrarchus labrax)

Describing and explaining the geographic within‐species variation in phenotypes (“phenogeography”) in the sea over a species distribution range is central to our understanding of a variety of eco‐evolutionary topics. However, phenogeographic studies that have a large potential to investigate adaptive variation are overcome by phylogeographic studies, still mainly focusing on neutral markers. How genotypic and phenotypic data could covary over large geographic scales remains poorly understood in marine species. We crossed 75 noninbred sires (five origins) and 26 dams (two origins; each side of a hybrid zone) in a factorial diallel cross in order to investigate geographic variation for early survival and sex ratio in the metapopulation of the European sea bass (Dicentrarchus labrax), a highly prized marine fish species. Full‐sib families (N = 1,950) were produced and reared in a common environment. Parentage assignment of 7,200 individuals was performed with seven microsatellite markers. Generalized linear models showed significant additive effects for both traits and pleiotropy between traits. A significant nonadditive genetic effect was detected. Different expression of traits and distinct relative performances were found for reciprocal crosses involving populations located on each side of the main hybrid zone located at the Almeria‐Oran front, illustrating asymmetric reproductive isolation. The poor fitness performance observed for the Western Mediterranean population of sea bass is discussed as it represents the main source of seed hatchery production, but also because it potentially illustrates nonadaptive introgression and maladaptation.     

A polygenic hypothesis for sex determination in the European sea bass Dicentrarchus labrax

Polygenic sex determination, although suspected in several species, is thought to be evolutionarily unstable and has been proven in very few cases. In the European sea bass, temperature is known to influence the sex ratio. We set up a factorial mating, producing 5.893 individuals from 253 full-sib families, all reared in a single batch to avoid any between-families environmental effects. The proportion of females in the offspring was 18.3%, with a large variation between families. Interpreting sex as a threshold trait, the heritability estimate was 0.62 +/- 0.12. The observed distribution of family sex ratios was in accordance with a polygenic model or with a four-sex-factors system with environmental variance and could not be explained by any genetic model without environmental variance. We showed that there was a positive genetic correlation between weight and sex (r(A) = 0.50 +/- 0.09), apart from the phenotypic sex dimorphism in favor of females. This supports the hypothesis that a minimum size is required for sea bass juveniles to differentiate as females. An evolution of sex ratio by frequency-dependent selection is expected during the domestication process of Dicentrarchus labrax populations, raising concern about the release of such fish in the wild.     

Fetal and maternal factors associated with infant mortality in vervet monkeys

Background Causes of infant death remain unknown in significant proportions of human and non‐human primate pregnancies. Methods A closed breeding colony with high rates of infant mortality had pregnancies assessed (n = 153) by fetal measurements and maternal characteristics. Infant outcome was classified as neonatal death (stillborn or died <48 hours from birth), postnatal death (died 2–30 days) or surviving (alive after 30 days). Results Fetal size did not predict outcome. Poor maternal glycemic control and low social ranking increased odds for adverse outcome (OR = 3.72, P = 0.01 and 2.27, P = 0.04, respectively). Male sex was over‐represented in stillbirths (P = 0.04), and many were macrosomic, but size did not associate with maternal glycemic control measured as glycated hemoglobin A1c. Postnatally dead infants were smaller (P < 0.01), which associated with behavioral factors and glycemic control. Conclusions Fetal growth estimates predicted gestational age but not fetal outcome. Maternal social status and metabolic health, particularly glycemic control, increased risks of adverse pregnancy outcome.     

Serotonergic influences on life-history outcomes in free-ranging male rhesus macaques

Several studies have demonstrated that nonhuman primate males with low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) exhibit antisocial behavior patterns. Included in these deleterious patterns are impulse control deficits associated with violence and premature death. No studies to date have longitudinally studied the long-term outcome of young subjects with low CSF 5-HIAA concentrations as they mature into adults. In this study we examined longitudinal relations among serotonergic and dopaminergic functioning, as reflected in CSF metabolite concentrations, aggression, age at emigration, dominance rank, and mortality in free-ranging rhesus macaque (Macaca mulatta) males. Our results indicate long-term consistency of individual differences in levels of 5-HIAA in CSF in the subject population from the juvenile period of development through adulthood. We found a significant negative correlation between 5-HIAA concentrations measured in juveniles and rates of high-intensity aggression in the same animals as adults. Further, CSF 5-HIAA concentrations were lower in juveniles that died than in animals that survived. For the young animals that migrated there was a positive correlation between CSF 5-HIAA concentration and age at emigration, whereas for the animals that remained in their troop until later in sexual maturity there was a negative correlation between CSF 5-HIAA concentration and age of emigration. After animals emigrated to a new troop, social dominance rank in the new troop was positively correlated with early family social dominance rank, but inversely correlated with juvenile CSF 5-HIAA concentrations. Taken together, our findings suggest that males with low central serotonin levels early in life delay migration and show high levels of violence and premature death, but the males that survive achieve high rank. These findings indicate that longitudinal measures of serotonergic and dopaminergic functioning are predictive of major life-history outcomes in nonhuman primate males. Low concentrations of CSF 5-HIAA are associated with negative life-history patterns characterized by social instability and excessive aggression, and positive life-history patterns characterized by higher dominance rank.     

A new membrane electrode for the detection of antibody.

A new membrane electrode sensitive to specific antibody is described which incorporates dinitrophenyl antigen in polyvinyl chloride matrix membrane on to the surface of a solid-state graphite-loaded epoxy-resin electrode. The sensitivity of the electrode is based on the ionophoric property of the dinitrophenyl antigen. Response curves for the potassium ion and its specific antibody are reported.