A comparative study of higher plant diversity and communities on opencast sites of varying age and adjacent undisturbed areas

A survey of three habitat types (woodland, hedgerow and pasture) on opencast sites of varying age and adjacent undisturbed sites N,W. of Durham was undertaken. Time since disturbance seems to be the primary influence on the development of organic content of the soils on opencast sites and the corresponding reduction in pH; soil water content is variable but is generally lower on recently restored and thus more consolidated soils. The quality of soil on the opencast woodland sites selected stress-tolerant ruderal plants as constant members of the community, the troughs in the plantations provided a suitable niche for bryophytes and liverworts. The plant diversity of pastures was comparable both on and off opencast sites due to similar farming practise (eg. ploughing and re-seeding). The ground flora of hedgerows was influenced also by aspect and was more diverse when protected from grazing by livestock by a fence

Solution structure of the Hop TPR2A domain and investigation of target druggability by NMR, biochemical and in silico approaches

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in tumour biology by promoting the stabilisation and activity of oncogenic ‘client’ proteins. Inhibition of Hsp90 by small-molecule drugs, acting via its ATP hydrolysis site, has shown promise as a molecularly targeted cancer therapy. Owing to the importance of Hop and other tetratricopeptide repeat (TPR)-containing cochaperones in regulating Hsp90 activity, the Hsp90-TPR domain interface is an alternative site for inhibitors, which could result in effects distinct from ATP site binders. The TPR binding site of Hsp90 cochaperones includes a shallow, positively charged groove that poses a significant challenge for druggability. Herein, we report the apo, solution-state structure of Hop TPR2A which enables this target for NMR-based screening approaches. We have designed prototype TPR ligands that mimic key native ‘carboxylate clamp’ interactions between Hsp90 and its TPR cochaperones and show that they block binding between Hop TPR2A and the Hsp90 C-terminal MEEVD peptide. We confirm direct TPR-binding of these ligands by mapping 1H–15N HSQC chemical shift perturbations to our new NMR structure. Our work provides a novel structure, a thorough assessment of druggability and robust screening approaches that may offer a potential route, albeit difficult, to address the chemically challenging nature of the Hop TPR2A target, with relevance to other TPR domain interactors

Enzymatic activities and functional interdependencies of Bacillus subtilis lipoteichoic acid synthesis enzymes

Lipoteichoic acid (LTA) is an important cell wall polymer in Gram-positive bacteria. The enzyme responsible for polyglycerolphosphate LTA synthesis is LtaS, first described in Staphylococcus aureus. Four LtaS orthologues, LtaSBS, YfnI, YqgS and YvgJ, are present in Bacillus subtilis. Using an in vitro enzyme assay, we determined that all four proteins are Mn2+-dependent metal enzymes that use phosphatidylglycerol as a substrate. We show that LtaSBS, YfnI and YqgS can produce polymers, suggesting that these three proteins are bona-fide LTA synthases while YvgJ functions as an LTA primase, as indicated by the accumulation of a GroP-Glc2-DAG glycolipid. Western blot analysis of LTA produced by ltaSBS, yfnI, yqgS and yvgJ single, triple and the quadruple mutant, showed that LTA production was only abolished in the quadruple and the YvgJ-only expressing mutant. B. subtilis strains expressing YfnI in the absence of LtaSBS produced LTA of retarded mobility, presumably caused by an increase in chain length as suggested by a structural analysis of purified LTA. Taken together, the presented results indicate that the mere presence or absence of LTA cannot account for cell division and sporulation defects observed in the absence of individual enzymes and revealed an unexpected enzymatic interdependency of LtaS-type proteins in B. subtilis

Multifactorial discrimination, discrimination salience, and prevalent experiences of internalized homophobia in middle-aged and older MSM

Objectives: We sought to test whether discrimination salience and multifactorial discrimination were associated with prevalent experiences of internalized homophobia among middle-aged and older men who have sex with men (MSM). Methods: We analyzed data from 498 middle-aged and older MSM from the Multicenter AIDS Cohort Study (MACS) who reported any lifetime discrimination experience. We estimated the prevalence ratio of current internalized homophobia using multivariable Poisson regressions, accounting for discrimination salience, multifactorial discrimination, and covariates. We then assessed whether multifactorial discrimination moderated the association between discrimination salience and internalized homophobia. Results: Over half (56.4%) of our sample reported any current experience of internalized homophobia. More than two-thirds reported multifactorial discrimination (68.2%) and more than one-third (36.7%) reported moderate-to-high discrimination salience. Increases in discrimination salience (PR = 1.11; 95% CI: 1.03-1.20) were associated with any current internalized homophobia among middle-aged and older MSM. Multifactorial discrimination was not statistically associated with internalized homophobia and did not moderate the association between discrimination salience and internalized homophobia. Conclusions: Our study underscores internalized homophobia as a persisting concern among MSM in midlife and older adulthood. Our findings suggest that salience, as a characteristic of discrimination experiences, may have a greater impact on internalized homophobia compared with exposure. Future research efforts should assess facets of discrimination salience, such as severity, frequency, and chronicity, to better understand how discrimination shapes psychosocial well-being across the life course. Mental health advocates at policy, organizational, and community levels should aim to reduce intersectional stigma and address individual experiences of internalized homophobia

Debris disk size distributions: steady state collisional evolution with P-R drag and other loss processes

We present a new scheme for determining the shape of the size distribution, and its evolution, for collisional cascades of planetesimals undergoing destructive collisions and loss processes like Poynting-Robertson drag. The scheme treats the steady state portion of the cascade by equating mass loss and gain in each size bin; the smallest particles are expected to reach steady state on their collision timescale, while larger particles retain their primordial distribution. For collision-dominated disks, steady state means that mass loss rates in logarithmic size bins are independent of size. This prescription reproduces the expected two phase size distribution, with ripples above the blow-out size, and above the transition to gravity-dominated planetesimal strength. The scheme also reproduces the expected evolution of disk mass, and of dust mass, but is computationally much faster than evolving distributions forward in time. For low-mass disks, P-R drag causes a turnover at small sizes to a size distribution that is set by the redistribution function (the mass distribution of fragments produced in collisions). Thus information about the redistribution function may be recovered by measuring the size distribution of particles undergoing loss by P-R drag, such as that traced by particles accreted onto Earth. Although cross-sectional area drops with 1/age^2 in the PR-dominated regime, dust mass falls as 1/age^2.8, underlining the importance of understanding which particle sizes contribute to an observation when considering how disk detectability evolves. Other loss processes are readily incorporated; we also discuss generalised power law loss rates, dynamical depletion, realistic radiation forces and stellar wind drag.Comment: Accepted for publication by Celestial Mechanics and Dynamical Astronomy (special issue on EXOPLANETS

Fusion of secretory vesicles isolated from rat liver

Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences

Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD

The relation between the column density structures and the magnetic field orientation in the Vela C molecular complex

We statistically evaluated the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, inferred from polarized thermal emission of Galactic dust observed by the Balloon-borne Large-Aperture Submillimetre Telescope for Polarimetry (BLASTPol) at 250, 350, and 500 μm, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.0 that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondence between (a) the trends in relative orientation between the column density structures and the projected magnetic field; and (b) the shape of the column density probability distribution functions (PDFs). In the sub-regions of Vela C dominated by one clear filamentary structure, or "ridges", where the high-column density tails of the PDFs are flatter, we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or "nests", where the maximum values of the column density are smaller than in the ridge-like sub-regions and the high-column density tails of the PDFs are steeper, such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region

A new approach to estimating hazard posed by debris flows in the Westfjords of Iceland

The aim of this study is to improve the assessment of hazard posed by debris flows to the people and settlements of northwest Iceland by studying very recent examples from above the town of Ísafjörður and other nearby localities. Debris flows are a recognised hazard in the region: above Ísafjörður, they occur with particularly high frequency and have appreciable volumes (up to 14 000 m3). We have used airborne laser altimeter (LiDAR) and differential Global Positioning System (GPS) data to produce isopach maps of flows that occurred in 1999, 2007, and 2008. Our data show that these flows begin depositing at higher slope gradients and are also more mobile than hillslope debris flows reported by other authors. Above a 19° slope, erosion is initiated independent of the distance along the flowpath. Using the isopach maps and associated field observations, we have found a relationship between ground slope and patterns in deposition volume. We have used this finding as a basis for an empirical model that enables an estimate of the total travel distance and final thickness of future debris flows to be calculated. This has enabled us to identify areas of the town which are at risk; some of these are not obvious without this analysis. This model is notable for its simplicity, which allows future debris flow characteristics to be predicted without the need to determine the precise fluid dynamic parameters of the flow such as viscosity and velocity, which are required to implement more complex models