Long-term observation of adsorbed heavy metal ions in sediment samples by MRI

Recently, we have reported studies of transport and sorption of heavy metal ions in water-saturated quartz sand columns under relatively fast water flow. In these experiments, clear indications for a fast and strong adsorption of the ions to the sediment could be found. Here we report the findings in a series of other experiments performed under static conditions. In this case, much higher concentrations of ions are adsorbed to the sand and remain immobile over time scales of more than a year. Changes in the MRI contrast observed for the sediment areas with the adsorbed ions indicate rearrangements in the distribution of the ions during the first days after administration to the sediment. EDX-studies of the ion distribution after several days indicate a spatially inhomogeneous distribution of adsorbed ions on the surface of the quartz sand. If the adsorbed ions are subjected to flow, a part of adsorbed ions moves away with the water flow. Also all ions are rapidly accessible to acid leaching

Neanderthal subsistence at Chez-Pinaud Jonzac (Charente-Maritime, France): A kill site dominated by reindeer remains, but with a horse-laden diet?

During the MIS 4 in Southwestern France, Quina Neanderthal from the north of the Aquitaine was characterized by a hunting specialization on the reindeer and the lack of diversity in their diet. They developed task-specific locations dedicated to the capture, the butchery, and the consumption of reindeer, and the whole society seems, in this region, to be dependent on this food resource. In this context, the site of Chez-Pinaud at Jonzac (France) occupies a specific place. First, interpreted as a reindeer kill and butchery site, the recent recovery of the site underlines the importance of the large ungulate (horse and bison) to the faunal spectrum (30% of the NISP). Considering the quantity of meat and grease that these species can provide to hunters, the new zooarchaeological analyses suggest that at least the horse may have played a major role in the diet of the Neanderthal population. Since Jonzac is one of the largest sites for this period, these results relativize the importance of reindeer specialization of the Quina population and the lack of diversityl in their diet

Fluxbrane Inflation

As a first step towards inflation in genuinely F-theoretic setups, we propose a scenario where the inflaton is the relative position of two 7-branes on holomorphic 4-cycles. Non-supersymmetric gauge flux induces an attractive inter-brane potential. The latter is sufficiently flat in the supergravity regime of large volume moduli. Thus, in contrast to brane-antibrane inflation, fluxbrane inflation does not require warping. We calculate the inflaton potential both in the supergravity approximation and via an open-string one-loop computation on toroidal backgrounds. This leads us to propose a generalisation to genuine Calabi-Yau manifolds. We also comment on competing F-term effects. The end of inflation is marked by the condensation of tachyonic recombination fields between the 7-branes, triggering the formation of a bound state described as a stable extension along the 7-brane divisor. Hence our model fits in the framework of hybrid D-term inflation. We work out the main phenomenological properties of our D-term inflaton potential. In particular, our scenario of D7/D7 inflation avoids the familiar observational constraints associated with cosmic strings.Comment: 49 pages, 3 figures; v3: refs adde

A Three-Hybrid Approach to Scanning the Proteome for Targets of Small Molecule Kinase Inhibitors

AbstractIn this study, we explored the application of a yeast three-hybrid (Y3H)-based compound/protein display system to scanning the proteome for targets of kinase inhibitors. Various known cyclin-dependent kinase (CDK) inhibitors, including purine and indenopyrazole analogs, were displayed in the form of methotrexate-based hybrid ligands and deployed in cDNA library or yeast cell array-based screening formats. For all inhibitors, known cell cycle CDKs as well as novel candidate CDK-like and/or CDK-unrelated kinase targets could be identified, many of which were independently confirmed using secondary enzyme assays and affinity chromatography. The Y3H system described here may prove generally useful in the discovery of candidate drug targets

The POT1-TPP1 telomere complex is a telomerase processivity factor

Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 ( protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1 - TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62923/1/nature05454.pd

Cancer survivors’ experiences of a community-based cancer-specific exercise programme: results of an exploratory survey

Purpose Exercise levels often decline following cancer diagnosis despite growing evidence of its benefits. Treatment side-effects, older age, lack of confidence and opportunity to exercise with others in similar circumstances influence this. Our study explored the experiences of people attending a cancer-specific community-based exercise programme (CU Fitter™). Methods A survey distributed to those attending the programme gathered demographic/clinical information, self-reported exercise levels, information provision and barriers to/benefits of exercise. Results Sixty surveys were evaluable from 65/100 returned (62% female, 68% >60yrs, 66% breast/prostate cancer). Most (68%) were receiving treatment. 68% attended classes once or twice weekly. 55% received exercise advice after diagnosis, usually from their hospital doctor/nurse. More (73%) had read about exercising, but less used the internet to source information (32%). Self-reported exercise levels were higher currently than before diagnosis (p=0.05). 48% said their primary barrier to exercising was the physical impact of cancer/treatment. Improving fitness/health (40%) and social support (16%) were the most important gains from the programme. Many (67%) had made other lifestyle changes and intented to keep (50%), or increase (30%) exercising. Conclusions This community-based cancer-specific exercise approach engaged people with cancer and showed physical, psychological, and social benefits. Implications for cancer survivors Community grown exercise initiatives bring cancer survivors together creating their own supportive environment. Combining this with instructors familiar with the population and providing an open-ended service may prove particularly motivating and beneficial. Further work is required to provide evidence for this

Association of polymorphisms in HCN4 with mood disorders and obsessive compulsive disorder

Hyperpolarization activated cyclic nucleotide-gated (HCN) potassium channels are implicated in the control of neuronal excitability and are expressed widely in the brain. HCN4 is expressed in brain regions relevant to mood and anxiety disorders including specific thalamic nuclei, the basolateral amygdala, and the midbrain dopamine system. We therefore examined the association of HCN4 with a group of mood and anxiety disorders. We genotyped nine tag SNPs in the HCN4 gene using Sequenom iPLEX Gold technology in 285 Caucasian patients with DSM-IV mood disorders and/or obsessive compulsive disorder and 384 Caucasian controls. HCN4 polymorphisms were analyzed using single marker and haplotype-based association methods. Three SNPs showed nominal association in our population (rs12905211, rs3859014, rs498005). SNP rs12905211 maintained significance after Bonferroni correction, with allele T and haplotype CTC overrepresented in cases. These findings suggest HCN4 as a genetic susceptibility factor for mood and anxiety disorders; however, these results will require replication using a larger sample

Fluxbranes: Moduli Stabilisation and Inflation

Fluxbrane inflation is a stringy version of D-term inflation in which two fluxed D7-branes move towards each other until their (relative) gauge flux annihilates. Compared to brane-antibrane inflation, the leading-order inflationary potential of this scenario is much flatter. In the present paper we first discuss a new explicit moduli stabilisation procedure combining the F- and D-term scalar potentials: It is based on fluxed D7-branes in a geometry with three large four-cycles of hierarchically different volumes. Subsequently, we combine this moduli stabilisation with the fluxbrane inflation idea, demonstrating in particular that CMB data (including cosmic string constraints) can be explained within our setup of hierarchical large volume CY compactifications. We also indicate how the eta-problem is expected to re-emerge through higher-order corrections and how it might be overcome by further refinements of our model. Finally, we explain why recently raised concerns about constant FI terms do not affect the consistent, string-derived variant of D-term inflation discussed in this paper.Comment: In section 3 an improved model is discusse

Unique Properties of Eukaryote-Type Actin and Profilin Horizontally Transferred to Cyanobacteria

A eukaryote-type actin and its binding protein profilin encoded on a genomic island in the cyanobacterium Microcystis aeruginosa PCC 7806 co-localize to form a hollow, spherical enclosure occupying a considerable intracellular space as shown by in vivo fluorescence microscopy. Biochemical and biophysical characterization reveals key differences between these proteins and their eukaryotic homologs. Small-angle X-ray scattering shows that the actin assembles into elongated, filamentous polymers which can be visualized microscopically with fluorescent phalloidin. Whereas rabbit actin forms thin cylindrical filaments about 100 µm in length, cyanobacterial actin polymers resemble a ribbon, arrest polymerization at 5-10 µm and tend to form irregular multi-strand assemblies. While eukaryotic profilin is a specific actin monomer binding protein, cyanobacterial profilin shows the unprecedented property of decorating actin filaments. Electron micrographs show that cyanobacterial profilin stimulates actin filament bundling and stabilizes their lateral alignment into heteropolymeric sheets from which the observed hollow enclosure may be formed. We hypothesize that adaptation to the confined space of a bacterial cell devoid of binding proteins usually regulating actin polymerization in eukaryotes has driven the co-evolution of cyanobacterial actin and profilin, giving rise to an intracellular entity