Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

How pregnancy can affect autoimmune diseases progression?

Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother’s circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.     

An amyloid organelle, solid-state NMR evidence for cross-β assembly of gas vesicles

Functional amyloids have been identified in a wide range of organisms, taking on a variety of biological roles and being controlled by remarkable mechanisms of directed assembly. Here, we report that amyloid fibrils constitute the ribs of the buoyancy organelles of Anabaena flos-aquae. The walls of these gas-filled vesicles are known to comprise a single protein, GvpA, arranged in a low pitch helix. However, the tertiary and quaternary structures have been elusive. Using solid-state NMR correlation spectroscopy we find detailed evidence for an extended cross-β structure. This amyloid assembly helps to account for the strength and amphiphilic properties of the vesicle wall. Buoyancy organelles thus dramatically extend the scope of known functional amyloids.     

A palaeoparasitological analysis of rodent coprolites from the Cueva Huenul 1 archaeological site in Patagonia (Argentina)

The aim of the present study was to examine the parasite fauna present in rodent coprolites collected from Cueva Huenul 1 (CH1), northern Neuquén (Patagonia, Argentina), an archaeological site that provides stratified sequences of archaeological and palaeontological remains dating from the Late Pleistocene/Early Holocene Transition to the Late Holocene period. Twenty rodent coprolites collected from different sedimentary units from the site, with ages ranging from 13.844 ± 75-1.416 ± 37 years BP, were examined for parasites. Each coprolite was processed as a whole: rehydrated, homogenised, spontaneously sedimented and examined using light microscopy. The coprolites and the eggs of any parasites present were described, measured and photographed. In all, 158 parasite eggs were found in 10 coprolites. The faeces were positive for Viscachataenia quadrata Denegri, Dopchiz, Elissondo & Beveridge and Monoecocestus sp. Beddard (Cestoda: Anoplocephalidae) and for Heteroxynema (Cavioxyura) viscaciae Sutton & Hugot (Nematoda: Oxyuridae). The coprolites examined were tentatively attributed to Lagidium viscacia Molina (Mammalia, Rodentia, Caviomorpha, Chinchillidae). The life cycles of these parasites are discussed.     

Interspecific Interactions and the Scope for Parent-Offspring Conflict: High Mite Density Temporarily Changes the Trade-Off between Offspring Size and Number in the Burying Beetle,Nicrophorus vespilloides

Parents have a limited amount of resources to invest in reproduction and commonly trade-off how much they invest in offspring size (or quality) versus brood size. A negative relationship between offspring size and number has been shown in numerous taxa and it underpins evolutionary conflicts of interest between parents and their young. For example, previous work on vertebrates shows that selection favours mothers that produce more offspring, at the expense of individual offspring size, yet favours offspring that have relatively few siblings and therefore attain a greater size at independence. Here we analyse how this trade-off is temporarily affected by stochastic variation in the intensity of interspecific interactions. We examined the effect of the mite Poecilochirus carabi on the relationship between offspring size and number in the burying beetle, Nicrophorus vespilloides. We manipulated the initial number of mites in the reproductive event (by introducing either no mites, 4 mites, 10 mites, or 16 mites), and assessed the effect on the brood. We found a similar trade-off between offspring size and number in all treatments, except in the ''16 mite'' treatment where the correlation between offspring number and size flattened considerably. This effect arose because larvae in small broods failed to attain a high mass by dispersal. Our results show that variation in the intensity of interspecific interactions can temporarily change the strength of the trade-off between offspring size and number. In this study, high densities of mites prevented individual offspring from attaining their optimal weight, thus potentially temporarily biasing the outcome of parent-offspring conflict in favour of parents.     

Solid-State NMR Evidence for Inequivalent GvpA Subunits in Gas Vesicles

Gas vesicles are organelles that provide buoyancy to the aquatic microorganisms that harbor them. The gas vesicle shell consists almost exclusively of the hydrophobic 70-residue gas vesicle protein A, arranged in an ordered array. Solid-state NMR spectra of intact collapsed gas vesicles from the cyanobacterium Anabaena flos-aquae show duplication of certain gas vesicle protein A resonances, indicating that specific sites experience at least two different local environments. Interpretation of these results in terms of an asymmetric dimer repeat unit can reconcile otherwise conflicting features of the primary, secondary, tertiary, and quaternary structures of the gas vesicle protein. In particular, the asymmetric dimer can explain how the hydrogen bonds in the β-sheet portion of the molecule can be oriented optimally for strength while promoting stabilizing aromatic and electrostatic side-chain interactions among highly conserved residues and creating a large hydrophobic surface suitable for preventing water condensation inside the vesicle.     

Social immunity of the family: parental contributions to a public good modulated by brood size

Social immunity refers to any immune defence that benefits others, besides the individual that mounts the response. Since contributions to social immunity are known to be personally costly, they are contributions to a public good. However, individuals vary in their contributions to this public good and it is unclear why. Here we investigate whether they are responding to contributions made by others with experiments on burying beetle (Nicrophorus vespilloides) families. In this species, females, males and larvae each contribute to social immunity through the application of antimicrobial exudates upon the carrion breeding resource. We show experimentally that mothers reduce their contributions to social immunity when raising large broods, and test two contrasting hypotheses to explain why. Either mothers are treating social immunity as a public good, investing less in social immunity when their offspring collectively contribute more, or mothers are trading off investment in social immunity with investment in parental care. Overall, our experiments yield no evidence to support the existence of a trade-off between social immunity and other parental care traits: we found no evidence of a trade-off in terms of time allocated to each activity, nor did the relationship between social immunity and brood size change with female condition. Instead, and consistent with predictions from models of public goods games, we found that higher quality mothers contributed more to social immunity. Therefore our results suggest that mothers are playing a public goods game with their offspring to determine their personal contribution to the defence of the carrion breeding resource.     

Interspecific interactions change the outcome of sexual conflict over prehatching parental investment in the burying beetle Nicrophorus vespilloides

Sexual conflict arises when the optimal reproductive strategy differs for males and females. It is associated with every reproductive stage, yet few studies have considered how the outcome may be changed by interactions with other species. Here, we show that phoretic mites Poecilochirus carabi change the outcome of sexual conflict over the supply of prehatching parental investment in the burying beetle Nicrophorus vespilloides. Burying beetles require a small dead vertebrate for reproduction, which they prepare by shaving it, rolling up the flesh, and burying it. When pairs were given a medium‐sized mouse to prepare (13–16 g), mites changed how the costs of reproduction were divided between the sexes, with males then sustaining greater costs than females. We found no equivalent difference when pairs prepared larger or smaller carcasses. Thus, our experiment shows that the outcome of sexual conflict over prehatching parental investment is changed by interactions with other species during reproduction.     

Synthesis and antidiabetic activity of morpholinothiazolyl-2,4-thiazolidindione derivatives

We report the synthesis and the in vitro insulin releasing and glucose uptake activity of the morpholino thiazolyl-2,4-thiazolidinediones (1-15). Compounds 5, 11-15 (at lower concentration; 0.001?mg/ml) were able to increase insulin release in the presence of 5.6 mmol/l glucose. The compounds, except derivative 3 show an increase of glucose uptake. Various compounds are interesting potential antidiabetic leads showing pancreatic and extrapancreatic effects.