Diet and mobility in a late neolithic population of coastal oman inferred from radiocarbon dating and stable isotope analysis

In Oman, the presence of highly productive marine environments, coupled with relatively limited land resources, have led to intense exploitation of coastal resources, but the question of the seasonality of occupation of coastal sites remains open. Our aim is to evaluate the contribution of marine resources to the diet of the Neolithic population of Ra's al‐Hamra 5 (RH‐5) to shed new light on its mobility, using stable isotopes and radiocarbon (¹⁴C) dating as dietary tracers. Charcoal, shell, human bone and enamel apatite from eight contemporary graves were sampled. Graves are thought to provide the best chance to obtain marine and terrestrial remains that were contemporary with the human remains in order to calculate the marine reservoir effect (MRE) for this period. Inter‐individual variation in human bone apatite δ¹³C value is small, suggesting a homogenous diet. Bone apatite ¹⁴C ages are very close to the shell ages while enamel is significantly younger and plots near the charcoal ages. Older enamel ages were obtained when a stronger acetic treatment was used, demonstrating that the young ages are due to diagenetic alteration rather than a diachronic change in diet and that only bone apatite retained in vivo dietary signals. Bone ages indicate a heavy reliance on marine resources and it is therefore unlikely that the individuals analyzed here were leaving the coast seasonally, although mobility along the coast cannot be excluded. Am J Phys Anthropol 153:353–364, 2014. © 2013 Wiley Periodicals, Inc.     

Cutting edge: Protective effect of CX3CR1+ dendritic cells in a vaccinia virus pulmonary infection model

The protective host immune response to viral infections requires both effective innate and adaptive immune responses. Cross-talk between the two responses is coordinated by the chemokine network and professional APCs such as dendritic cells (DCs). In mice, subpopulations of myeloid DCs in peripheral tissues such as lungs and in blood express CX3CR1 depending on the inflammation state. We thus examined the host response of mice deficient in the chemokine receptor CX3CR1 to an intranasal vaccinia virus infection. CX3CR1-deficient mice displayed significantly more severe morbidity and mortality compared with control wild-type mice within 10 d following vaccinia virus infection. CX3CR1(-/-) mice had increased viral loads and a reduced T cell response compared with wild-type mice. Finally, an adoptive transfer of CX3CR1(+/+) DCs completely protected CX3CR1(-/-) mice to a previously lethal infection. This study therefore opens up the possibility of novel antiviral therapeutics targeting lung DC recruitment.     

Endophytic fungi from Combretum leprosum with potential anticancer and antifungal activity

The recent increase in human diseases and cancers requires new drugs to combat them. Sources have been found in rare microorganisms, those from extreme habitats, and from endophytes. In this study, the biological activity of endophytic fungi associated with the Brazilian medicinal plant Combretum leprosum was assessed. Cytotoxic and antiproliferative effects were evaluated using seven human cancer cells lines (HeLa, ECV304, B16F10, J744, P388, Jurkat and k562). In addition the minimum inhibitory concentration (MIC) against pathogenic human fungal was determined using four Candida species and the filamentous fungi Cryptococcus neoformans and Trichophyton rubrum. A compound from extracts of phylotype Aspergillus oryzae CFE108 exhibited the most significant cytotoxicity effect against histiocytic sarcoma J774 (IC₅₀ of 0.80 μg?mL^?1), leukemia Jurkat (IC₅₀ of 0.89 μg?mL^?1), bladder carcinoma ECV304 (IC₅₀ of 3.08 μg?mL^?1) and cervical cancer HeLa (IC₅₀ of 2.97 μg?mL^?1). The extract from phylotypes Fusarium oxysporum CFE177 displayed antifungal activity and inhibited the growth of Candida glabrata (4 μg?mL^?1) as well as that of C. neoformans and T. rubrum with the lowest MIC being 62.5 μg?mL^?1. In addition, the fractions from A. oryzae CFE108 showed marked morphological activity (rounding up) on endothelial cells (tEnd.1 cells), which is indicative of potential antivascular activity. Our results indicate that the endophytes associated with this medicinal plant may be a source of novel drugs.     

A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

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Expression,purification and kinetic characterisation of human tissue transglutaminase

The expression of soluble recombinant transglutaminase (TGase) has proven to be a challenge for many research groups. Herein, we report a complementary method for the expression, in BL21(DE3) Escherichia coli, of recombinant human tissue transglutaminase (hTG2) whose solubility is enhanced through N-terminal fusion to glutathione S-transferase (GST). Moreover, we report the cleavage of the GST tag using PreScission? Protease (PSP) and purification of hTG2 in its untagged form, distinctively suitable for subsequent studies of its remarkable conformational equilibrium. The effects of co-solvents and storage conditions on stability of purified hTG2 are also reported. Furthermore, we demonstrate for the first time the use of a convenient chromogenic assay to measure the activity of the human enzyme. The utility of this assay was demonstrated in the measurement of the kinetic parameters of a wide variety of substrates and inhibitors of both hTG2 and the extensively studied guinea pig liver TGase. Finally, comparison of these results provides further evidence for the functional similarity of the two enzymes.     

Nickel superoxide dismutase: structural and functional roles of Cys2 and Cys6

Nickel superoxide dismutase (NiSOD) is unique among the family of superoxide dismutase enzymes in that it coordinates Cys residues (Cys2 and Cys6) to the redox-active metal center and exhibits a hexameric quaternary structure. To assess the role of the Cys residues with respect to the activity of NiSOD, mutations of Cys2 and Cys6 to Ser (C2S-NiSOD, C6S-NiSOD, and C2S/C6S-NiSOD) were carried out. The resulting mutants do not catalyze the disproportionation of superoxide, but retain the hexameric structure found for wild-type NiSOD and bind Ni(II) ions in a 1:1 stoichiometry. X-ray absorption spectroscopic studies of the Cys mutants revealed that the nickel active-site structure for each mutant resembles that of C2S/C6S-NiSOD and demonstrate that mutation of either Cys2 or Cys6 inhibits coordination of the remaining Cys residue. Mutation of one or both Cys residue(s) in NiSOD induces the conversion of the low-spin Ni(II) site in the native enzyme to a high-spin Ni(II) center in the mutants. This result indicates that coordination of both Cys residues is required to generate the native low-spin configurations and maintain catalytic activity. Analysis of the quaternary structure of the Cys mutants by differential scanning calorimetry, mass spectrometry, and size-exclusion chromatography revealed that the Cys ligands, particularly Cys2, are also important for stabilizing the hexameric quaternary structure of the native enzyme.     

Spatial heterogeneity lowers rather than increases host–parasite specialization

Abiotic environmental heterogeneity can promote the evolution of diverse resource specialists, which in turn may increase the degree of host–parasite specialization. We coevolved Pseudomonas fluorescens and lytic phage ?2 in spatially structured populations, each consisting of two interconnected subpopulations evolving in the same or different nutrient media (homogeneous and heterogeneous environments, respectively). Counter to the normal expectation, host–parasite specialization was significantly lower in heterogeneous compared with homogeneous environments. This result could not be explained by dispersal homogenizing populations, as this would have resulted in the heterogeneous treatments having levels of specialization equal to or greater than that of the homogeneous environments. We argue that selection for costly generalists is greatest when the coevolving species are exposed to diverse environmental conditions and that this can provide an explanation for our results. A simple coevolutionary model of this process suggests that this can be a general mechanism by which environmental heterogeneity can reduce rather than increase host–parasite specialization.     

Triterpenoid saponins from a cytotoxic root extract of Sideroxylonfoetidissimum subsp. gaumeri

Evaluation of the cytotoxicity of an ethanolic root extract of Sideroxylonfoetidissimum subsp. gaumeri (Sapotaceae) revealed activity against the murine macrophage-like cell line RAW 264.7. Systematic bioassay-guided fractionation of this extract gave an active saponin-containing fraction from which four saponins were isolated. Use of 1D (¹H, ¹³C, DEPT135) and 2D (COSY, TOCSY, HSQC, and HMBC) NMR, mass spectrometry and sugar analysis gave their structures as 3-O-(β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, 3-O-β-d-glucopyranosyl-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, 3-O-(β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, and the known compound, 3-O-β-d-glucopyranosyl-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-protobassic acid. Two further saponins were obtained from the same fraction, but as a 5:4 mixture comprising 3-O-(β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid and 3-O-(β-d-apiofuranosyl-(1 → 3)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, respectively. This showed greater cytotoxicity (IC₅₀ = 11.9 ± 1.5 μg/ml) towards RAW 264.7 cells than the original extract (IC₅₀ = 39.5 ± 4.1 μg/ml), and the saponin-containing fraction derived from it (IC₅₀ = 33.7 ± 6.2 μg/ml).     

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing,Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review

Background

Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions.

Methods

A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes.

Findings

This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities.

Conclusions

There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.