Transient expression analysis of allelic variants of a VNTR in the dopamine transporter gene (DAT1)

BACKGROUND: The 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT1) has been associated with a range of psychiatric phenotypes, most notably attention-deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study we have characterised the genomic structure of the 9- and 10-repeat VNTR alleles, and directly examined the role of the polymorphism in mediating gene expression by measuring comparative in vitro cellular expression using a reporter-gene assay system. RESULTS: Differences in the sequence of the 9- and 10- repeat alleles were confirmed but no polymorphic differences were observed between individuals. There was no difference in expression of reporter gene constructs containing the two alleles. CONCLUSIONS: Our data suggests that this VNTR polymorphism may not have a direct effect on DAT1 expression and that the associations observed with psychiatric phenotypes may be mediated via linkage disequilibrium with other functional polymorphisms

Interpretable correlation descriptors for quantitative structure-activity relationships

<p>Abstract</p> <p>Background</p> <p>The topological maximum cross correlation (TMACC) descriptors are alignment-independent 2D descriptors for the derivation of QSARs. TMACC descriptors are generated using atomic properties determined by molecular topology. Previous validation (<it>J Chem Inf Model </it>2007, <b>47</b>: 626-634) of the TMACC descriptor suggests it is competitive with the current state of the art.</p> <p>Results</p> <p>Here, we illustrate the interpretability of the TMACC descriptors, through the analysis of the QSARs of inhibitors of angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR). In the case of the ACE inhibitors, the TMACC interpretation shows features specific to C-domain inhibition, which have not been explicitly identified in previous QSAR studies.</p> <p>Conclusions</p> <p>The TMACC interpretation can provide new insight into the structure-activity relationships studied. Freely available, open source software for generating the TMACC descriptors can be downloaded from <url>http://comp.chem.nottingham.ac.uk</url>.</p

Chandra X-ray Sources in the Collapsed-Core Globular Cluster M30 (NGC 7099)

We report the detection of six discrete, low-luminosity (Lx < 10^33 erg/s) X-ray sources, located within 12 arcsec of the center of the collapsed-core globular cluster M30 (NGC 7099), and a total of 13 sources within the half-mass radius, from a 50 ksec Chandra ACIS-S exposure. Three sources lie within the very small upper limit of 1.9 arcsec on the core radius. The brightest of the three core sources has a luminosity of Lx (0.5-6 keV) = 6x10^32 erg/s and a blackbody-like soft X-ray spectrum, which are both consistent with it being a quiescent low-mass X-ray binary (qLMXB). We have identified optical counterparts to four of the six central sources and a number of the outlying sources, using deep Hubble Space Telescope and ground-based imaging. While the two proposed counterparts that lie within the core may represent chance superpositions, the two identified central sources that lie outside of the core have X-ray and optical properties consistent with being CVs. Two additional sources outside of the core have possible active binary counterparts. We discuss the X-ray source population of M30 in light of its collapsed-core status.Comment: 18 pages, 13 figures (8 color), resubmitted to ApJ after incorporating referee comment

Identification Of Faint Chandra X-Ray Sources In The Core-Collapsed Globular Cluster NGC 6397: Evidence For A Bimodal Cataclysmic Variable Population

We have searched for optical identifications for 79 Chandra X-ray sources that lie within the half-mass radius of the nearby, core-collapsed globular cluster NGC 6397, using deep Hubble Space Telescope Advanced Camera for Surveys Wide Field Channel imaging in H alpha, R, and B. Photometry of these images allows us to classify candidate counterparts based on color-magnitude diagram location. In addition to recovering nine previously detected cataclysmic variables (CVs), we have identified six additional faint CV candidates, a total of 42 active binaries (ABs), two millisecond pulsars, one candidate active galactic nucleus, and one candidate interacting galaxy pair. Of the 79 sources, 69 have a plausible optical counterpart. The 15 likely and possible CVs in NGC 6397 mostly fall into two groups: a brighter group of six for which the optical emission is dominated by contributions from the secondary and accretion disk and a fainter group of seven for which the white dwarf dominates the optical emission. There are two possible transitional objects that lie between these groups. The faintest CVs likely lie near the minimum of the CV period distribution, where an accumulation is expected. The spatial distribution of the brighter CVs is much more centrally concentrated than those of the fainter CVs and the ABs. This may represent the result of an evolutionary process in which CVs are produced by dynamical interactions, such as exchange reactions, near the cluster center and are scattered to larger orbital radii, over their lifetimes, as they age and become fainter.NASA HST-GO-10257ANSF REU AST-0452975NSERCCIFARAstronom

Parenteral versus oral iron therapy for adults and children with chronic kidney disease

Background The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. Objectives To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD. Search methods In March 2010 we searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE and EMBASE without language restriction. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs in which oral and IV routes of iron administration were compared in adults and children with CKD. Data collection and analysis Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and for continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random‐effects model. Subgroup analysis and univariate meta‐regression were performed to investigate between study differences. Main results Twenty eight studies (2098 participants) were included. Risk of bias attributes were poorly performed and/or reported with low risk of bias reported in 12 (43%) studies for sequence generation, incomplete outcome reporting and selective outcome reporting and in 6 (16%) studies for allocation concealment. No study was blinded for participants, investigators and outcome assessors but all were considered at low risk of bias because the primary outcome of haemoglobin was a laboratory outcome and unlikely to be influenced by lack of blinding. Haemoglobin (22 studies, 1862 patients: MD 0.90 g/dL, 95% CI 0.44 to 1.37); ferritin (24 studies, 1751 patients: MD 243.25 μg/L, 95% CI 188.74 to 297.75); and transferrin saturation (18 studies, 1457 patients: MD 10.20%, 95% CI 5.56 to 14.83) were significantly increased by IV iron compared with oral iron. There was a significant reduction in erythropoiesis‐stimulating agent (ESA) dose in patients receiving dialysis who were treated with IV iron (9 studies, 487 patients: SMD ‐0.76, 95% CI ‐1.22 to ‐0.30). There was a high level of heterogeneity in all analyses. Mortality and cardiovascular morbidity did not differ significantly, but were reported in few studies. Gastrointestinal side effects were more common with oral iron, but hypotensive and allergic reactions were more common with IV iron. Authors' conclusions The included studies provide strong evidence for increased ferritin and transferrin saturation levels, together with a small increase in haemoglobin, in patients with CKD who were treated with IV iron compared with oral iron. From a limited body of evidence, we identified a significant reduction in ESA requirements in patients treated with IV iron, and found no significant difference in mortality. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient‐centred outcomes are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects

The hard quiescent spectrum of the neutron-star X-ray transient EXO 1745-248 in the globular cluster Terzan 5

We present a Chandra observation of the globular cluster Terzan 5 during times when the neutron-star X-ray transient EXO 1745-248 located in this cluster was in its quiescent state. We detected the quiescent system with a (0.5-10 keV) luminosity of ~2 x 10^{33} ergs/s. This is similar to several other neutron-star transients observed in their quiescent states. However, the quiescent X-ray spectrum of EXO 1745--48 was dominated by a hard power-law component instead of the soft component that usually dominates the quiescent emission of other neutron-star X-ray transients. This soft component could not conclusively be detected in EXO 1745-248 and we conclude that it contributed at most 10% of the quiescent flux in the energy range 0.5-10 keV. EXO 1745-248 is only the second neutron-star transient whose quiescent spectrum is dominated by the hard component (SAX J1808.4-3658 is the other one). We discuss possible explanations for this unusual behavior of EXO 1745-248, its relationship to other quiescent neutron-star systems, and the impact of our results on understanding quiescent X-ray binaries. We also discuss the implications of our results on the way the low-luminosity X-ray sources in globular clusters are classified.Comment: Accepted by ApJ Main Journal, September 22, 2004. Figure 2 is a color figur

Neurogenesis Deep Learning

Neural machine learning methods, such as deep neural networks (DNN), have achieved remarkable success in a number of complex data processing tasks. These methods have arguably had their strongest impact on tasks such as image and audio processing - data processing domains in which humans have long held clear advantages over conventional algorithms. In contrast to biological neural systems, which are capable of learning continuously, deep artificial networks have a limited ability for incorporating new information in an already trained network. As a result, methods for continuous learning are potentially highly impactful in enabling the application of deep networks to dynamic data sets. Here, inspired by the process of adult neurogenesis in the hippocampus, we explore the potential for adding new neurons to deep layers of artificial neural networks in order to facilitate their acquisition of novel information while preserving previously trained data representations. Our results on the MNIST handwritten digit dataset and the NIST SD 19 dataset, which includes lower and upper case letters and digits, demonstrate that neurogenesis is well suited for addressing the stability-plasticity dilemma that has long challenged adaptive machine learning algorithms.Comment: 8 pages, 8 figures, Accepted to 2017 International Joint Conference on Neural Networks (IJCNN 2017

Dietary patterns for adults with chronic kidney disease

This is the protocol for a review and there is no abstract. The objectives are as follows: This review will evaluate the benefits and harms of dietary patterns among adults with CKD (any stage including people with end-stage kidney disease (ESKD) treated with dialysis, transplantation or supportive care)