Is Telomere Length Socially Patterned? Evidence from the West of Scotland Twenty-07 Study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages.     

HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells

Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.     

Stretch-induced activation of ERK in myocytes is p38 and calcineurin-dependent

Activation of specific mitogen-activated protein kinases (MAPKs) has been suggested to be involved in phenotype modulation of cells subjected to mechanical strain, which may be common to different mechano-sensitive cell types. We have submitted C2C12 myocytes to a static stretch and examined its effect upon the activation of ERK. Stretch induced a rapid but transient activation of ERK. This activation was however prevented when cells were pre-treated with inhibitors of p38 and calcineurin. The dependence of strain-induced ERK activation upon p38 suggests a cross-talk between these two pathways when mediating a response to a mechanical stimulus in this cell type. This suggests that cross relationships between these MAP kinases may be of crucial importance for myocyte phenotype modulation and differentiation in response to a mechanical stimulus.     

Speciation,phase association and potential bioavailability of phosphorus on a Svalbard glacier

Glacier surfaces are known to harbour abundant and active microbial communities. Phosphorus has been shown to be deficient in glacial environments, and thus is one of the limits on microbial growth and activity. We quantified the phosphorus pool in cryoconite debris and the concentration of dissolved phosphorus in supraglacial water on Werenskioldbreen, a Svalbard glacier. The mean total P content of the cryoconite debris was ~2.2 mg g⁻¹, which is significantly more than would be expected in rock debris from local sources. 57% of this P was present in the fraction defined as organic P. It may account for the P in excess of the rock debris, and could be explained by allochthonous input of organic matter. The concentration of total dissolved P in supraglacial water was very low (5.2–8.5 μg l⁻¹), which was probably caused by efficient flushing and re-adsorption onto mineral surfaces. Dissolved organic P (DOP) was a very important component of the dissolved phosphorus pool on Werenskioldbreen, as concentrations of DOP typically exceeded those of dissolved inorganic P (or SRP) by more than four times in all the glacial water types. It is very difficult to assess whether P was limiting in this environment solely on the basis of the N:P ratios in the debris or biomass. There may be some degree of biological control over the C:N:P ratios in the debris, but the phosphorus cycling in the supraglacial environment on this glacier seems to be mainly controlled by physical and geochemical processes.     

Cartilage link protein interacts with neurocan, which shows hyaluronan binding characteristics different from CD44 and TSG-6

The interaction of neurocan with hyaluronan was qualitatively characterized with alkaline phosphatase fusion proteins secreted by mammalian cells. The wild type neurocan hyaluronan binding domain fused to alkaline phosphatase bound to immobilized hyaluronan under physiological as well as moderately hypertonic conditions, whereas its ability to bind to immobilized chondroitin sulfate dropped rapidly with increasing salt concentration. Strong hyaluronan binding ability was still evident when in both link modules within the hyaluronan binding domain a basic amino acid was mutated, which is well conserved among link modules of hyaluronan binding proteins. A strong enhancement of the binding of neurocan to immobilized hyaluronan was observed after preincubation of the immobilized hyaluronan with cartilage link protein. Moreover, this preincubation mediated also the binding of a fusion protein representing only the immunoglobulin module of neurocan linked to alkaline phosphatase, which showed no binding to immobilized hyaluronan alone. The interaction of the neurocan immunoglobulin module with link protein could also be shown by overlay blot analysis. These observations suggest that the hyaluronan binding characteristics of paired link modules are different from those of single link modules, and that the reported temporal co-expression of cartilage link protein and of neurocan in developing brain implicates the possibility of a cooperative function of these molecules.     

Low frequency of mutations in the core promoter and precore regions of hepatitis B virus in anti-HBe positive Brazilian carriers

Background  

Mutations in the core promoter and precore regions of the hepatitis B virus (HBV) genome, notably the double substitution (AGG to TGA) at nt positions 1762-1764 in the core promoter, and the precore stop codon mutation G to A at nt 1896, can often explain the anti-HBe phenotype in chronic carriers. However, the A1896 mutation is restricted to HBV isolates that have T at nt 1858. The double substitution at positions 1762-1764 has been described to occur preferentially in patients infected with strains showing C instead of T at nt 1858.     

Effect of different carbon sources on the enhanced biological phosphorus removal in a sequencing batch reactor

The effect of the different carbon sources acetate, acetate/glucose or glucose on the enhanced biological phosphorus removal (EBPR) process was studied by experiments under alternating anaerobic–aerobic conditions in one sequencing batch reactor for each carbon source. The glucose was consumed completely within the first 30 min of the anaerobic phase whereas acetate degradation was slow and incomplete. Phosphate was released independently of the carbon source during the whole anaerobic phase. The highest phosphate release (27 mg P l⁻¹) and polyhydroxyalkanoate (PHA) storage (20 mg C g⁻¹ dry matter (DM)) during the anaerobic phase as well as the highest polyphosphate (poly-P) (8 mg P g⁻¹ DM) and glycogen storage (17 mg C g⁻¹ DM) during the aerobic phase were observed with acetate. In contrast to other investigations, glycogen storage did not increase with glucose as substrate but was significantly smaller than with acetate. The PHA composition was also influenced strongly by the carbon source. The polyhydroxyvalerate (PHV) portion of the PHA was maximal 17% for acetate and 82% for glucose. Due to the strong influence of the carbon source on the PHA concentration and composition, PHA storage seems to regulate mainly the phosphate release and uptake. This revised version was published online in July 2006 with corrections to the Cover Date.     

Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates.

Waardenburg-Shah syndrome combines the reduced enteric nervous system characteristic of Hirschsprung's disease with reduced pigment cell number, although the cell biological basis of the disease is unclear. We have analysed a zebrafish Waardenburg-Shah syndrome model. We show that the colourless gene encodes a sox10 homologue, identify sox10 lesions in mutant alleles and rescue the mutant phenotype by ectopic sox10 expression. Using iontophoretic labelling of neural crest cells, we demonstrate that colourless mutant neural crest cells form ectomesenchymal fates. By contrast, neural crest cells which in wild types form non-ectomesenchymal fates generally fail to migrate and do not overtly differentiate. These cells die by apoptosis between 35 and 45 hours post fertilisation. We provide evidence that melanophore defects in colourless mutants can be largely explained by disruption of nacre/mitf expression. We propose that all defects of affected crest derivatives are consistent with a primary role for colourless/sox10 in specification of non-ectomesenchymal crest derivatives. This suggests a novel mechanism for the aetiology of Waardenburg-Shah syndrome in which affected neural crest derivatives fail to be generated from the neural crest.     

Significant decreases in the intensity of staining for proteins and protein thiols in basal-cell epitheliomas (basaliomas) as compared to normal skin

Microphotometric measurements of fast reacting protein thiols (PSHr) and proteins were performed on freshly frozen sections of samples from normal skin (26 cases as controls) and from 45 basal cell epitheliomas (basalioma; BCE). The intensity of the staining (E/micron2) for both proteins and PSHr was significantly higher in normal epidermis than in the adjacent dermis. The values of QE (quotient of values observed in the epidermis divided by those observed in the dermis) were calculated to be 3.48 for proteins (QE, Prot) and 4.62 for PSHr (QE, PSHr). In cases of BCE, significantly lower QE values were found: QE, Prot = 2.16 and QE, PSHr = 1.72. The decrease of QE, PSHr was due to a decrease in the staining intensity observed in the BCEs, whereas practically no changes occurred in the adjacent dermis. The decrease of QE, Prot was mainly caused by a decrease in the staining intensity in the BCE (by 68%) as well as in the adjacent dermis (by 36%). By dividing the mean extinction value (E/micron2) for PSHr by the E/micron2 for proteins, a new quotient, PSHr/Prot, is obtained which can serve as a quantitative measure of the content of the tissue proteins of PSHr. The proteins of normal epidermis contained more PSHr than dermal proteins. The proteins of BCEs also contained more PSHr than those of the adjacent dermis, but the PSHr/Prot values of both tissues were 1.5 to 1.6 times greater than the corresponding values for normal epidermis and dermis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)