Maternal and paternal care in the rock cavy,Kerodon rupestris,a South American hystricomorph rodent

The maternal and paternal behavior of Kerodon rupestris was examined. Quantitative differences between fathers and mothers and between mothers raising young with fathers present and with fathers absent were assessed. Growth rates of young raised by paired females and by lone females were compared. The male provides direct paternal care to the young by engaging in allogrooming, sniffing, and huddling. There is no significant difference between the sexes in the amount of contact promoting behavior given to the offspring, nor are the sexes significantly different in the amount of exploratory sniffing of the offspring. When the male is absent, the female spends a greater amount of time in contact with the young. Young raised by lone females gained significantly more weight than young raised by paired females. The suggestion that indirect paternal care acts to reduce female aggression to the young and relieve the energy expenditure burden of the female is discussed. The results indicate that social experience is gained at the expense of physical nurturing when the male is present.     

Personal model‐assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD

To elucidate the molecular mechanisms underlying non‐alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome‐scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD⁺ and glutathione (GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD⁺ repletion on the development of NAFLD, we added precursors for GSH and NAD⁺ biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof‐of‐concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.     

BID‐dependent release of mitochondrial SMAC dampens XIAP‐mediated immunity against Shigella

The X‐linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti‐apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase‐mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP‐mediated immune response by inducing the BID‐dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain‐dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization.     

Amphisexual parental behavior of a terrestrial breeding frog Eleutherodactylus johnstonei in Guyana

Parental care in Elcutherodactylus johnstonei, a terrestriallybreeding frog, was uniparental, but was uniparental, bu carewas provided by either sex. I tested Maynard Smith's evoluntionarilystable strategy, continous breeding model III, by examiningsocial and ecological conditions under which the provided parentalcare in Georgetown, Guyana, South America. During the long wetseason most males chosen by frmales as mates provided parentalcare. No males that acquired females through satellite behaviorand displacement competition provided care. Females providedparental care in most cases when males failed to do so, andsome returned to nests for 72 h, even after being repeatedlydriven away by attending males. Females initiated maternal careup to 72 h after oviposition following temporary removal ofmales. Male-biased operational sex ratios were significantlydifferent for wet and dry months, and no females provided carewhen rainfall was << mm. Additionally operational sexratio multiply regressed on paternal and maternal care and rainfallindicated that paternal and maternal care were significantlycorrelated with operational sex ratio. Rainfall was not relatedto opeational sex ratio. During the dryer months only malesprovided care. Males provided less care during weter months,when moe gravid females were avialable as mates. Significantto protect progeny. Although there was support for Maynard Smith'smodel of evolution of amphisexual cae form biparental care,it was difficult to ascertain clearly whether amphisexual parentalbehavior from either biparental bahiour or no care. This uncertailtyensues because the behaviour of females and males and developmentof progeny may have become coadapted after the initial evolutionof care in E. johnstonsi.     

Mutant Alleles at the Brown Locus Encoding Tyrosinase‐Related Protein‐1 (TRP‐1) Affect Proliferation of Mouse Melanocytes in Culture *

Tyrosinase related protein‐1 (TRP‐1) is a melanocyte‐specific gene product involved in eumelanin synthesis. Mutation in the Tyrp1 gene is associated with brown pelage in mouse and oculocutaneous albinism Type 3 in humans (OCA3). It has been demonstrated that TRP‐1 expresses DHICA oxidase activity in the murine system. However, its actual function in the human system is still unclear. The study was designed to determine the effects of mutation at two Typr1 alleles, namely the Tyrp1^b (brown) and Tyrp1^b‐cj (cordovan) compared with wild type Tyrp1^B (black) on melanocyte function and melanin biosynthesis. The most significant finding was that both of the Tyrp1 mutations (i.e. brown expressing a point mutation and cordovan expressing decreased amount of TRP‐1 protein) resulted in attenuation of cell proliferation rates. Neither necrosis nor apoptosis was responsible for the observed decrease in cell proliferation rates of the brown and cordovan melanocytes. Ultrastructural evaluation by electron microscopic analysis revealed that both mutations in Tyrp1 affected melanosome maturation without affecting its structure. These observations demonstrate that mutation in Tyrp1 compromised tyrosinase activity within the organelle. DOPA histochemistry revealed differences in melanosomal stages between black and brown melanocytes but not between black and cordovan melanocytes. There were no significant differences in tyrosine hydroxylase activities of tyrosinase and TRP‐1 in wild type black, brown and cordovan melanocyte cell lysates. We conclude that mutations in Tyrp1 compromise cell proliferation and melanosomal maturation in mouse melanocyte cultures.     

Bacteriophages and bacteriophage‐derived endolysins as potential therapeutics to combat Gram‐positive spore forming bacteria

Since their discovery in 1915, bacteriophages have been routinely used within Eastern Europe to treat a variety of bacterial infections. Although initially ignored by the West due to the success of antibiotics, increasing levels and diversity of antibiotic resistance is driving a renaissance for bacteriophage‐derived therapy, which is in part due to the highly specific nature of bacteriophages as well as their relative abundance. This review focuses on the bacteriophages and derived lysins of relevant Gram‐positive spore formers within the Bacillus cereus group and Clostridium genus that could have applications within the medical, food and environmental sectors.