Distant X-ray Galaxies: Insights from the Local Population

A full understanding of the origin of the hard X-ray background requires a complete and accurate census of the distant galaxies that produce it. Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths, which hinders efforts to perform this census. This chapter discusses the insights that can be obtained through comparison of the distant population to local X-ray galaxies, whose properties are well characterized. Such comparisons will ultimately aid investigations into the cosmic evolution of supermassive black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

Resolving the extragalactic hard X-ray background

The origin of the hard (2-10 keV) X-ray background has remained mysterious for over 35 years. Most of the soft (0.5-2 keV) X-ray background has been resolved into discrete sources, which are primarily quasars; however, these sources do not have the flat spectral shape required to match the X-ray background spectrum. Here we report the results of an X-ray survey 30 times more sensitive than previous studies in the hard band and four times more sensitive in the soft band. The sources detected in our survey account for at least 75 per cent of the hard X-ray background. The mean X-ray spectrum of these sources is in good agreement with that of the background. The X-ray emission from the majority of the detected sources is unambiguously associated with either the nuclei of otherwise normal bright galaxies or optically faint sources, which could either be active nuclei of dust enshrouded galaxies or the first quasars at very high redshifts.Comment: Nature article in pres

Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature

Smith-Magenis syndrome (SMS) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies. While the majority of SMS cases harbor an ~3.5 Mb common deletion on 17p11.2 that encompasses the retinoic acid induced-1 (RAI1) gene, some patients carry small intragenic deletions or point mutations in RAI1. We present data on two cases of Smith-Magenis syndrome with mutation of RAI1. Both cases are phenotypically consistent with SMS and RAI1 mutation but also have other anomalies not previously reported in SMS, including spontaneous pneumothoraces. These cases also illustrate variability in the SMS phenotype not previously shown for RAI1 mutation cases, including hearing loss, absence of self-abusive behaviours, and mild global delays. Sequencing of RAI1 revealed mutation of the same heptameric C-tract (CCCCCCC) in exon 3 in both cases (c.3103delC one case and and c.3103insC in the other), resulting in frameshift mutations. Of the seven reported frameshift mutations occurring in poly C-tracts in RAI1, four cases (~57%) occur at this heptameric C-tract. Collectively, these results indicate that this heptameric C-tract is a preferential hotspot for single nucleotide insertion/deletions (SNindels) and therefore, should be considered a primary target for analysis in patients suspected for mutations in RAI1. We expect that as more patients are sequenced for mutations in RAI1, the incidence of frameshift mutations in this hotspot will become more evident

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Alternative uses for co-products: Harnessing the potential of valuable compounds from meat processing chains

peer-reviewedOpportunities for exploiting the inherent value of protein-rich meat processing co-products, in the context of increased global demand for protein and for sustainable processing systems, are discussed. While direct consumption maybe the most profitable route for some, this approach is influenced greatly by local and cultural traditions. A more profitable and sustainable approach may be found in recognizing this readily available and under-utilised resource can provide high value components, such as proteins, with targeted high value functionality of relevance to a variety of sectors. Applications in food & beverages, petfood biomedical and nutrition arenas are discussed. Utilization of the raw material in its entirety is a necessary underlying principle in this approach to help maintain minimum waste generation. Understanding consumer attitudes to these products, in particular when used in food or beverage systems, is critical in optimizing commercialization strategies.This work forms part of the ReValueProtein Research Project (Grant Award No. 11/F/043) which is supported by the Irish Department of Agriculture, Food and the Marine (DAFM) and the Food Institutional Research Measure (FIRM) both funded by the Irish Government under the National Development Plan 2007–2013.Department of Agriculture, Food and the Marin

Composition and distribution of the peracarid crustacean fauna along a latitudinal transect off Victoria Land (Ross Sea, Antarctica) with special emphasis on the Cumacea

The following study was the first to describe composition and structure of the peracarid fauna systematically along a latitudinal transect off Victoria Land (Ross Sea, Antarctica). During the 19th Antarctic expedition of the Italian research vessel “Italica” in February 2004, macrobenthic samples were collected by means of a Rauschert dredge with a mesh size of 500 m at depths between 85 and 515 m. The composition of peracarid crustaceans, especially Cumacea was investigated. Peracarida contributed 63% to the total abundance of the fauna. The peracarid samples were dominated by amphipods (66%), whereas cumaceans were represented with 7%. Previously, only 13 cumacean species were known, now the number of species recorded from the Ross Sea increased to 34. Thus, the cumacean fauna of the Ross Sea, which was regarded as the poorest in terms of species richness, has to be considered as equivalent to that of other high Antarctic areas. Most important cumacean families concerning abundance and species richness were Leuconidae, Nannastacidae, and Diastylidae. Cumacean diversity was lowest at the northernmost area (Cape Adare). At the area off Coulman Island, which is characterized by muddy sediment, diversity was highest. Diversity and species number were higher at the deeper stations and abundance increased with latitude. A review of the bathymetric distribution of the Cumacea from the Ross Sea reveals that most species distribute across the Antarctic continental shelf and slope. So far, only few deep-sea records justify the assumption of a shallow-water–deep-sea relationship in some species of Ross Sea Cumacea, which is discussed from an evolutionary point of view

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc