IFN-gamma polymorphisms (IFN-gamma +2109 and IFN-gamma +3810) are associated with severe hepatic fibrosis in human hepatic schistosomiasis (Schistosoma mansoni)

Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).     

Neuronal untranslated BC1 RNA: targeted gene elimination in mice

Despite the potentially important roles of untranslated RNAs in cellular form or function, genes encoding such RNAs have until now received surprisingly little attention. One such gene encodes BC1 RNA, a small non-mRNA that is delivered to dendritic microdomains in neurons. We have now eliminated the BC1 RNA gene in mice. Three independent founder lines were established from separate embryonic stem cells. The mutant mice appeared to be healthy and showed no anatomical or neurological abnormalities. The gross brain morphology was unaltered in such mice, as were the subcellular distributions of two prototypical dendritic mRNAs (encoding MAP2 and CaMKIIalpha). Due to the relatively recent evolutionary origin of the gene, we expected molecular and behavioral consequences to be subtle. Behavioral analyses, to be reported separately, indicate that the lack of BC1 RNA appears to reduce exploratory activity.     

Human tibia bone marrow: defining a model for the study of haemodynamics as a function of age by near infrared spectroscopy

A human model allowing the non-invasive study of bone marrow haemodynamics has been developed. A decrease in postischaemic tissue reperfusion capability (postischaemic hyperaemia) as a function of age (range 25-72 years) was observed both in the human tibia and tibialis anterior muscle. In the tibia bone marrow the reperfusion capability started to decrease after 50 years and was lower than for muscle for all the age range. Mean basal muscle O(2) saturation (80.8% at 25 years) decreases as a function of age (-0.35%+/-0.13% per year) whereas it remains constant for bone marrow (84.8+/-2.8%). A Monte Carlo simulation has been performed to evaluate the accuracy of the derived O(2) saturation measurements and has shown that this parameter is robust even in the presence of substantial noise. It has also been demonstrated that it is necessary to use a multi wavelength NIR spectrometer and a second derivative based fitting algorithm to obtain reliable measurements from the bone marrow, and that the tissue scattering changes occurring during the protocol do not allow the use of the standard near infrared spectroscopy algorithms. The human tibia bone marrow model presented here and the related measurement technique should enable access to new areas of physiological research.     

Age-specific reproductive success in a long-lived bird: do older parents resist stress better?

In many vertebrates, reproductive performance increases with advancing age but mechanisms involved in such a pattern remain poorly studied. One potential mechanism may be the hormonal stress response, which shifts energy investment away from reproduction and redirects it towards survival. In birds, this stress response is achieved through a release of corticosterone and is also accompanied by a decrease in circulating prolactin, a hormone involved widely in regulating parental cares. It has been predicted that, when the value of the current reproduction is high relative to the value of future reproduction and survival, as it is expected to be in older adults, the stress response should be attenuated to ensure that reproduction is not inhibited. We tested this hypothesis by measuring the corticosterone and prolactin responses of known-age (8-36 years old) incubating snow petrels (Pagadroma nivea) to a standardized capture/handling stress protocol. We also investigated whether an attenuation of the stress responses will correlate with a lower occurrence of egg neglect, a frequently observed behaviour in snow petrels. The probability of successfully fledging a chick increased from 6 years to 12 years before stabilizing after 12 years of age. Corticosterone response to stress was unaffected by age. Prolactin response to stress, however, was influenced clearly by age: in both sexes older breeders had higher stress-induced prolactin levels than younger ones. This was due to an increasing attenuation of the prolactin response to stress with advancing age in females, and in males this was due to a probably higher intrinsic capacity of older males to secrete prolactin. Moreover, higher stress-induced prolactin levels were correlated with a lower probability of neglecting the egg. In young breeders, the combination of a robust corticosterone increase with a lower ability to maintain prolactin secretion during acute stress is probably one of the functional causes of their lower incubation commitment. We suggest that the ability to maintain a threshold level of prolactin during a stressful situation may be an important physiological mechanism involved in the improvement of reproductive performance with advancing age in long-lived birds.     

Sensitive and specific LC-ESI-MS/MS method for the determination of a styrylquinoline, BA011FZ041, a potent HIV anti-integrase agent, in rat plasma

A LC-MS/MS method was validated for the determination of BA011FZ041, a styrylquinoline derivative. After addition of BA011FZ055 as internal standard (IS), the method involved solid phase extraction (SPE), LC separation with an ether-phenyl column and quantification by MS/MS after positive ESI. The calibration curve, ranging from 1 to 500 ng/mL was fitted to a 1/x-weighted quadratic regression model. Lower limit of quantification (LLOQ) was 1 ng/mL using 100 microL of plasma. Intra- and inter-assay precision and accuracy values were within the regulatory limits. The method was successfully applied to the determination of BA011FZ041 in rat plasma and PBMCs after i.v. dosing.     

Senescence rates and late adulthood reproductive success are strongly influenced by personality in a long-lived seabird

Studies are increasingly demonstrating that individuals differ in their rate of ageing, and this is postulated to emerge from a trade-off between current and future reproduction. Recent theory predicts a correlation between individual personality and life-history strategy, and from this comes the prediction that personality may predict the intensity of senescence. Here we show that boldness correlates with reproductive success and foraging behaviour in wandering albatrosses, with strong sex-specific differences. Shy males show a strong decline in reproductive performance with age, and bold females have lower reproductive success in later adulthood. In both sexes, bolder birds have longer foraging trips and gain more mass per trip as they get older. However, the benefit of this behaviour appears to differ between the sexes, such that it is only matched by high reproductive success in males. Together our results suggest that personality linked foraging adaptations with age are strongly sex-specific in their fitness benefits and that the impact of boldness on senescence is linked to ecological parameters.     

Plumage colour variations in the Agapornis genus: a review

The genus Agapornis consists of nine small African parrot species that are globally well known as pets, but are also found in their native habitat. Illegal trapping, poaching and habitat destruction are the main threats these birds face in the wild. In aviculture, Agapornis breeding is highly popular all across the globe. Birds are mainly selected based on their plumage colour variations but very little molecular research has been conducted on this topic. There are 30 known colour variations amongst the nine species and most of these are inherited as Mendelian traits. However, to date none of the genes or polymorphisms linked to these variations have been identified or verified. Due to unethical breeding practices, the need for the development of molecular tests such as identification verification tests or species identity tests is growing. Future research is paramount to ensure the conservation of wild populations as well as aiding breeders in improving breeding strategies.     

Chirality in amino acids beyond the Cα configuration

Based on a CSD search, a meta‐analysis of 1179 structures of 19 natural amino acids H₃NC_αH(R)C′(O)O and their derivatives H₃NC_αH(R)C′(O)O(H/R/M), protonated, esterified, or coordinated at the carboxylic group, shows that the chirality chain with its two steps, established in the preceding paper for alanine, can be extended to natural amino acids. High diastereoselectivities are observed in the induction from the L configuration at C_α to the ?ψ and +ψ conformations, which in turn distort the planar carboxylic group C_αC′(O_cis)O_trans to asymmetric flat tetrahedra, showing that the chirality chain is an integral part of natural amino acids.