The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. Methods In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Results Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. Conclusions None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioningThis work was supported by the EU-project Disc Regeneration (NMP3-LA-2008-213904). Technical assistance of Iris Baum and the whole animal surgery team of the Institute of Orthopaedic Research and Biomechanics, Ulm, are gratefully acknowledged. DDAHA hydrogels were kindly provided by Cristina Longinotti (DDAHA, Anika Therapeutics, Abano Therme, Italy)

Properties of Galaxies in and around Voids

Two surveys for intrinsically faint galaxies towards nearby voids have been conducted at the MPI f\"ur Astronomie, Heidelberg. One selected targets from a new diameter limited ($\Phi \ge 5''$) catalog with morphological criteria while the other used digitized objective prism Schmidt plates to select mainly HII dwarf galaxies. For some 450 galaxies, redshifts and other optical data were obtained. We studied the spatial distribution of the sample objects, their luminosity function, and their intrinsic properties. Most of the galaxies belong to already well known sheets and filaments. But we found about a dozen highly isolated galaxies in each sample (nearest neighborhood distance $\ge 3 h_{75}^{-1} Mpc$). These tend to populate additional structures and are not distributed homogeneously throughout the voids. As our results on 'void galaxies' still suffer from small sample statistics, I also tried to combine similar existing surveys of nearby voids to get further hints on the larger structure and on the luminosity function of the isolated galaxies. No differences in the luminosity function of sheet and void galaxies could be found. The optical and infrared properties of both samples are in the normal range for samples dominated by late-type dwarfs. Follow-up HI studies show that the isolated dwarfs in both samples have unusual high amount of neutral gas for a given luminosity.Comment: 10 pages, 4 figures, latex, to appear in the proceedings of the 'Ringberg workshop on Large Scale Structure', hold Sep. 23-28, 199

Testimonial Injustice and Vulnerability: A Qualitative Analysis of Participation in the Court of Protection

This article explores participation in Court of Protection (COP) proceedings by people considered vulnerable. The paper is based on original data obtained from observing COP proceedings and reviewing COP case files. It is argued that the observed absence of the subject of proceedings is a form of testimonial injustice, that is, a failure to value a person in their capacity as a giver of knowledge. The issue of competence to give evidence is considered but it is argued that it is not the formal evidential rules that prohibit a vulnerable adult from giving evidence. Instead, it is the result of a persistent assumption that they are inherently vulnerable and therefore lack credibility as a knowledge giver. This assumption results in the voices of vulnerable adults being routinely absent from legal proceedings. It is argued that having a voice in the courtroom is essential and has a number of intrinsic and instrumental benefits. The paper concludes with a discussion about the implications of the research, including the current trend towards the increased use of special measures, and recommends a presumption in favour of the subject of COP proceedings giving evidence

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Cosmic rays and molecular clouds

This paper deals with the cosmic-ray penetration into molecular clouds and with the related gamma--ray emission. High energy cosmic rays interact with the dense gas and produce neutral pions which in turn decay into two gamma rays. This makes molecular clouds potential sources of gamma rays, especially if they are located in the vicinity of a powerful accelerator that injects cosmic rays in the interstellar medium. The amplitude and duration in time of the cosmic--ray overdensity around a given source depend on how quickly cosmic rays diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray observations of molecular clouds can be used both to locate the sources of cosmic rays and to constrain the properties of cosmic-ray diffusion in the Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics 2012, 27 pages, 10 figure

The changing form of Antarctic biodiversity

Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewher

The role of protected areas in the avoidance of anthropogenic conversion in a high pressure region : a matching method analysis in the core region of the brazilian cerrado

Global efforts to avoid anthropogenic conversion of natural habitat rely heavily on the establishment of protected areas. Studies that evaluate the effectiveness of these areas with a focus on preserving the natural habitat define effectiveness as a measure of the influence of protected areas on total avoided conversion. Changes in the estimated effectiveness are related to local and regional differences, evaluation methods, restriction categories that include the protected areas, and other characteristics. The overall objective of this study was to evaluate the effectiveness of protected areas to prevent the advance of the conversion of natural areas in the core region of the Brazil’s Cerrado Biome, taking into account the influence of the restriction degree, governmental sphere, time since the establishment of the protected area units, and the size of the area on the performance of protected areas. The evaluation was conducted using matching methods and took into account the following two fundamental issues: control of statistical biases caused by the influence of covariates on the likelihood of anthropogenic conversion and the non-randomness of the allocation of protected areas throughout the territory (spatial correlation effect) and the control of statistical bias caused by the influence of auto-correlation and leakage effect. Using a sample design that is not based on ways to control these biases may result in outcomes that underestimate or overestimate the effectiveness of those units. The matching method accounted for a bias reduction in 94–99% of the estimation of the average effect of protected areas on anthropogenic conversion and allowed us to obtain results with a reduced influence of the auto-correlation and leakage effects. Most protected areas had a positive influence on the maintenance of natural habitats, although wide variation in this effectiveness was dependent on the type, restriction, governmental sphere, size and age group of the unit

Listening Difficulties in Children: Behavior and Brain Activation Produced by Dichotic Listening of CV Syllables

Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6–13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD (n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation