Potential mechanisms of avian sex manipulation

The aim of this review is to consider the potential mechanisms birds may use to manipulate the sex of their progeny, and the possible role played by maternal hormones. Over the past few years there has been a surge of reports documenting the ability of birds to overcome the rigid process of chromosomal sex determination. However, while many of these studies leave us in little doubt that mechanisms allowing birds to achieve this feat do exist, we are only left with tantalizing suggestions as to what the precise mechanism or mechanisms may be. The quest to elucidate them is made no easier by the fact that a variety of environmental conditions have been invoked in relation to sex manipulation, and there is no reason to assume that any particular mechanism is conserved among the vast diversity of species that can achieve it. In fact, a number of intriguing proposals have been put forward. We begin by briefly reviewing some of the most recent examples of this phenomenon before highlighting some of the more plausible mechanisms, drawing on recent work from a variety of taxa. In birds, females are the heterogametic sex and so non-Mendelian segregation of the sex chromosomes could conceivably be under maternal control. Another suggestion is that follicles that ultimately give rise to males and females grow at different rates. Alternatively, the female might selectively abort embryos or 'dump lay' eggs of a particular sex, deny certain ova a chance of ovulation, fertilization or zygote formation, or selectively provision eggs so that there is sex-specific embryonic mortality. The ideas outlined in this review provide good starting points for testing the hypotheses both experimentally (behaviourally and physiologically) and theoretically.     

A structural biologist's view of the oestrogen receptor

Here we review the results that have emerged from our structural studies on the oestrogen receptor ligand-binding domain (ER-LBD). The effects of agonists and antagonists on the structure of ER- and ERβ-LBDs are examined. In addition, the findings from structural studies of ER-LBD in complex with peptide fragments corresponding to the NR-box II and III modules of the p160 coactivator TIF2 are discussed in the context of the assembly of ER:coactivator complexes. Together these studies have broadened our understanding of ER function by providing a unique insight into ER's ligand specificity, it's ability to interact with coactivators and the structural changes that underlie receptor agonism and antagonism.     

Pregnancy outcome for nomadic Turkana pastoralists of Kenya

The outcome of an individual pregnancy is a key component of overall reproductive success and is strongly influenced by environmental, behavioral, and biological variation within populations. This prospective study examined the outcomes of 68 pregnancies among nomadic Turkana of Kenya from July 1993 to July 1994. A total of 12 women experienced pregnancy losses, and 3 women experienced live births with a subsequent perinatal death. The following characteristics are associated with increased risk for experiencing a fetal or perinatal death: severe morbidity episodes, shorter nonpregnant intervals, lower third-trimester weight, higher third-trimester summed skinfolds but limited third-trimester reduction in summed skinfolds, and higher activity levels late in gestation. Turkana newborns measured within 48 hr of birth (n = 19) weighed an average of 2,860 +/- 640 g and had a mean ponderal index of 2.72 +/- 0.46. Variation in birth weight was predicted by preterm delivery, delivery during the wet season, and maternal morbidity levels. Birth length averaged 50.8 +/- 6.8 cm and was positively influenced by full term delivery, better maternal health, and birth during the dry season. These results suggest complicated pathways linking the physical environment, subsistence requirements, heterogeneity in maternal fitness, behavior, and pregnancy outcome. The results augment the larger picture of reproductive success for Turkana nomads who live in a highly variable savanna environment.     

Avian Egg Odour Encodes Information on Embryo Sex,Fertility and Development

Avian chemical communication is a rapidly emerging field, but has been hampered by a critical lack of information on volatile chemicals that communicate ecologically relevant information (semiochemicals). A possible, but as yet unexplored, function of olfaction and chemical communication in birds is in parent-embryo and embryo-embryo communication. Communication between parents and developing embryos may act to mediate parental behaviour, while communication between embryos can control the synchronicity of hatching. Embryonic vocalisations and vibrations have been implicated as a means of communication during the later stages of development but in the early stages, before embryos are capable of independent movement and vocalisation, this is not possible. Here we show that volatiles emitted from developing eggs of Japanese quail (Coturnix japonica) convey information on egg fertility, along with the sex and developmental status of the embryo. Specifically, egg volatiles changed over the course of incubation, differed between fertile and infertile eggs, and were predictive of embryo sex as early as day 1 of incubation. Egg odours therefore have the potential to facilitate parent-embryo and embryo-embryo interactions by allowing the assessment of key measures of embryonic development long before this is possible through other modalities. It also opens up the intriguing possibility that parents may be able to glean further relevant information from egg volatiles, such as the health, viability and heritage of embryos. By determining information conveyed by egg-derived volatiles, we hope to stimulate further investigation into the ecological role of egg odours.     

Osteological,Biomolecular and Geochemical Examination of an Early Anglo-Saxon Case of Lepromatous Leprosy

We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21–35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America.     

The interplay of cyclic stretch and vascular endothelial growth factor in regulating the initial steps for angiogenesis

Angiogenesis is regulated by chemical and mechanical factors in vivo. The regulatory role of mechanical factors and how chemical and mechanical angiogenic regulators work in concert remains to be explored. We investigated the effect of cyclic uniaxial stretch (20%, 1 Hz), with and without the stimulation of vascular endothelial growth factor (VEGF), on sprouting angiogenesis by employing a stretchable three‐dimensional cell culture model. When compared to static controls, stretch alone significantly increased the density of endothelial sprouts, and these sprouts aligned perpendicular to the direction of stretch. The Rho‐associated kinase (ROCK) inhibitor Y27632 suppressed stretch‐induced sprouting angiogenesis and associated sprout alignment. While VEGF is a potent angiogenic stimulus through ROCK‐dependent pathways, the combination of VEGF and stretch did not have an additive effect on angiogenesis. In the presence of VEGF stimulation, the ROCK inhibitor suppressed stretch‐induced sprout alignment but did not affect stretch‐induced sprout density; in contrast, the receptor tyrosine kinase (RTK) inhibitor sunitinib had no effect on stretch‐induced alignment but trended toward suppressed stretch‐induced sprout density. Our results suggest that the formation of sprouts and their directionality do not have completely identical regulatory pathways, and thus it is possible to separately manipulate the number and pattern of new sprouts. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:248–257, 2015     

The 'human revolution' in lowland tropical Southeast Asia: the antiquity and behavior of anatomically modern humans at Niah Cave (Sarawak, Borneo)

Recent research in Europe, Africa, and Southeast Asia suggests that we can no longer assume a direct and exclusive link between anatomically modern humans and behavioral modernity (the 'human revolution'), and assume that the presence of either one implies the presence of the other: discussions of the emergence of cultural complexity have to proceed with greater scrutiny of the evidence on a site-by-site basis to establish secure associations between the archaeology present there and the hominins who created it. This paper presents one such case study: Niah Cave in Sarawak on the island of Borneo, famous for the discovery in 1958 in the West Mouth of the Great Cave of a modern human skull, the 'Deep Skull,' controversially associated with radiocarbon dates of ca. 40,000 years before the present. A new chronostratigraphy has been developed through a re-investigation of the lithostratigraphy left by the earlier excavations, AMS-dating using three different comparative pre-treatments including ABOX of charcoal, and U-series using the Diffusion-Absorption model applied to fragments of bones from the Deep Skull itself. Stratigraphic reasons for earlier uncertainties about the antiquity of the skull are examined, and it is shown not to be an 'intrusive' artifact. It was probably excavated from fluvial-pond-desiccation deposits that accumulated episodically in a shallow basin immediately behind the cave entrance lip, in a climate that ranged from times of comparative aridity with complete desiccation, to episodes of greater surface wetness, changes attributed to regional climatic fluctuations. Vegetation outside the cave varied significantly over time, including wet lowland forest, montane forest, savannah, and grassland. The new dates and the lithostratigraphy relate the Deep Skull to evidence of episodes of human activity that range in date from ca. 46,000 to ca. 34,000 years ago. Initial investigations of sediment scorching, pollen, palynomorphs, phytoliths, plant macrofossils, and starch grains recovered from existing exposures, and of vertebrates from the current and the earlier excavations, suggest that human foraging during these times was marked by habitat-tailored hunting technologies, the collection and processing of toxic plants for consumption, and, perhaps, the use of fire at some forest-edges. The Niah evidence demonstrates the sophisticated nature of the subsistence behavior developed by modern humans to exploit the tropical environments that they encountered in Southeast Asia, including rainforest.     

DNA accelerates the inhibition of human cathepsin V by serpins

A balance between proteolytic activity and protease inhibition is crucial to the appropriate function of many biological processes. There is mounting evidence for the presence of both papain-like cysteine proteases and serpins with a corresponding inhibitory activity in the nucleus. Well characterized examples of cofactors fine tuning serpin activity in the extracellular milieu are known, but such modulation has not been studied for protease-serpin interactions within the cell. Accordingly, we present an investigation into the effect of a DNA-rich environment on the interaction between model serpins (MENT and SCCA-1), cysteine proteases (human cathepsin V and human cathepsin L), and cystatin A. DNA was indeed found to accelerate the rate at which MENT inhibited cathepsin V, a human orthologue of mammalian cathepsin L, up to 50-fold, but unexpectedly this effect was primarily effected via the protease and secondarily by the recruitment of the DNA as a "template" onto which cathepsin V and MENT are bound. Notably, the protease-mediated effect was found to correspond both with an altered substrate turnover and a conformational change within the protease. Consistent with this, cystatin inhibition, which relies on occlusion of the active site rather than the substrate-like behavior of serpins, was unaltered by DNA. This represents the first example of modulation of serpin inhibition of cysteine proteases by a co-factor and reveals a mechanism for differential regulation of cathepsin proteolytic activity in a DNA-rich environment.     

Characterizing early events associated with the activation of target genes by 1,25-dihydroxyvitamin D3 in mouse kidney and intestine in vivo

In this report, we explore the interaction of the vitamin D receptor (VDR) at regulatory sites within both the Cyp24a1 and the Trpv6 genes using chromatin immunoprecipitation techniques in a mouse model in vivo. We show that exogenous 1,25(OH)(2)D(3) induces rapid VDR and RXR (retinoid X receptor) binding to the Cyp24a1 gene in both the kidney and the intestine and to the Trpv6 gene in the intestine. Separate studies of Trpv6 in vitro suggest that VDR binding occurs directly to VDR response elements located -2 and -4 kb upstream of the TSS. VDR binding is dose-dependent, demonstrating EC(50) values that are comparable with those for the induction of both Cyp24a1 and Trpv6 mRNA. Importantly, interaction of the VDR with these targets results in rapid changes in histone 4 acetylation as well as the recruitment of RNA polymerase II. The presence of both VDR and RNA polymerase II at these sites declines between 3-6 h, whereas the changes observed in acetylation decrease more slowly. Finally, we show that whereas mediator protein 1 is recruited to the Cyp24a1 promoter in the intestine, this coactivator is apparently not required for Trpv6 activation. These studies provide the first evidence for 1,25(OH)(2)D(3)-induced VDR interaction at key target genes in vivo, revealing the consequences of that interaction on the Cyp24a1 and Trpv6 genes.