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

Evaluation of a Rapid Immunochromatographic ODK-0901 Test for Detection of Pneumococcal Antigen in Middle Ear Fluids and Nasopharyngeal Secretions

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs

A standardized approach to treat complex aortic valve endocarditis: a case series

Background Surgical treatment of complicated aortic valve endocarditis often is challenging, even for experienced surgeons. We aim at demonstrating a standardized surgical approach by stentless bioprostheses for the treatment of aortic valve endocarditis complicated by paravalvular abscess formation. MethodsSixteen patients presenting with aortic valve endocarditis (4 native and 12 prosthetic valves) and paravalvular abscess formation at various localizations and to different extents were treated by a standardized approach using stentless bioprostheses. The procedure consisted of thorough debridement, root replacement with reimplantation of the coronary arteries and correction of accompanying pathologies (aortoventricular and aortomitral dehiscence, septum derangements, Gerbode defect, total atrioventricular conduction block, mitral and tricuspid valve involvement).ResultsAll highly complex patients included (14 males and 2 females; median age 63 years [range 31–77]) could be successfully treated with stentless bioprostheses as aortic root replacement. Radical surgical debridement of infected tissue with anatomical recontruction was feasible. Although predicted operative mortality was high (median logarithmic EuroSCORE I of 40.7 [range 12.8–68.3]), in-hospital and 30-day mortality rates were favorable (18.8 and 12.5% respectively). ConclusionsRepair of active aortic valve endocarditis complicated by paravalvular abscess formation and destruction of the left ventricular outflow tract with stentless bioprosthesis is a valuable option for both native and prosthetic valves. It presents a standardized approach with a high success rate for complete debridement, is readily available, and yields comparable clinical outcomes to the historical gold standard, repair by homografts. Additionally, use of one type of prosthesis reduces logistical issues and purchasing costs

Selective Depletion of Eosinophils or Neutrophils in Mice Impacts the Efficiency of Apoptotic Cell Clearance in the Thymus

Developing thymocytes undergo a rigorous selection process to ensure that the mature T cell population expresses a T cell receptor (TCR) repertoire that can functionally interact with major histocompatibility complexes (MHC). Over 90% of thymocytes fail this selection process and die. A small number of macrophages within the thymus are responsible for clearing the large number of dying thymocytes that must be continuously cleared. We studied the capacity of thymic macrophages to clear apoptotic cells under acute circumstances. This was done by synchronously inducing cell death in the thymus and then monitoring the clearance of apoptotic thymocytes. Interestingly, acute cell death was shown to recruit large numbers of CD11b+ cells into the thymus. In the absence of a minor CSF-1 dependent population of macrophages, the recruitment of these CD11b+ cells into the thymus was greatly reduced and the clearance of apoptotic cells was disrupted. To assess a possible role for the CD11b+ cells in the clearance of apoptotic cells, we analyzed mice deficient for eosinophils and mice with defective trafficking of neutrophils. Failure to attract either eosinophils or neutrophils to the thymus resulted in the impaired clearance of apoptotic cells. These results suggested that there is crosstalk between cells of the innate immune system that is necessary for maximizing the efficiency of apoptotic cell removal

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Who Eats Whom in a Pool? A Comparative Study of Prey Selectivity by Predatory Aquatic Insects

Predatory aquatic insects are a diverse group comprising top predators in small fishless water bodies. Knowledge of their diet composition is fragmentary, which hinders the understanding of mechanisms maintaining their high local diversity and of their impacts on local food web structure and dynamics. We conducted multiple-choice predation experiments using nine common species of predatory aquatic insects, including adult and larval Coleoptera, adult Heteroptera and larval Odonata, and complemented them with literature survey of similar experiments. All predators in our experiments fed selectively on the seven prey species offered, and vulnerability to predation varied strongly between the prey. The predators most often preferred dipteran larvae; previous studies further reported preferences for cladocerans. Diet overlaps between all predator pairs and predator overlaps between all prey pairs were non-zero. Modularity analysis separated all primarily nectonic predator and prey species from two groups of large and small benthic predators and their prey. These results, together with limited evidence from the literature, suggest a highly interconnected food web with several modules, in which similarly sized predators from the same microhabitat are likely to compete strongly for resources in the field (observed Pianka’s diet overlap indices >0.85). Our experiments further imply that ontogenetic diet shifts are common in predatory aquatic insects, although we observed higher diet overlaps than previously reported. Hence, individuals may or may not shift between food web modules during ontogeny

Rapid Accumulation of Polymorphonuclear Neutrophils in the Corpus luteum during Prostaglandin F2α-Induced Luteolysis in the Cow

Prostaglandin F2α (PGF2α) induces luteolysis within a few days in cows, and immune cells increase in number in the regressing corpus luteum (CL), implying that luteolysis is an inflammatory-like immune response. We investigated the rapid change in polymorphonuclear neutrophil (PMN) numbers in response to PGF2α administration as the first cells recruited to inflammatory sites, together with mRNA of interleukin-8 (IL-8: neutrophil chemoattractant) and P-selectin (leukocyte adhesion molecule) in the bovine CL. CLs were collected by ovariectomy at various times after PGF2α injection. The number of PMNs was increased at 5 min after PGF2α administration, whereas IL-8 and P-selectin mRNA increased at 30 min and 2 h, respectively. PGF2α directly stimulated P-selectin protein expression at 5–30 min in luteal endothelial cells (LECs). Moreover, PGF2α enhanced PMN adhesion to LECs, and this enhancement by PGF2α was inhibited by anti-P-selectin antibody, suggesting that P-selectin expression by PGF2α is crucial in PMN migration. In conclusion, PGF2α rapidly induces the accumulation of PMNs into the bovine CL at 5 min and enhances PMN adhesion via P-selectin expression in LECs. It is suggested that luteolytic cascade by PGF2α may involve an acute inflammatory-like response due to rapidly infiltrated PMNs

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall

Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition

Cognitive dysfunction is a core feature of dementia and a prominent feature in psychiatric disease. As non-redundant regulators of intracellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relevant to learning, memory, and higher cognitive functions. Phosphodiesterase-4B (PDE4B) is an important phosphodiesterase in the hippocampal formation, is a major Disrupted in Schizophrenia 1 (DISC1) binding partner and is itself a risk gene for psychiatric illness. To define the effects of specific inhibition of the PDE4B subtype, we generated mice with a catalytic domain mutant form of PDE4B (Y358C) that has decreased ability to hydrolyze cAMP. Structural modelling predictions of decreased function and impaired binding with DISC1 were confirmed in cell assays. Phenotypic characterization of the PDE4BY358C mice revealed facilitated phosphorylation of CREB, decreased binding to DISC1, and upregulation of DISC1 and β-Arrestin in hippocampus and amygdala. In behavioural assays, PDE4BY358C mice displayed decreased anxiety and increased exploration, as well as cognitive enhancement across several tests of learning and memory, consistent with synaptic changes including enhanced long-term potentiation and impaired depotentiation ex vivo. PDE4BY358C mice also demonstrated enhanced neurogenesis. Contextual fear memory, though intact at 24 hours, was decreased at 7 days in PDE4BY358C mice, an effect replicated pharmacologically with a non-selective PDE4 inhibitor, implicating cAMP signalling by PDE4B in a very late phase of consolidation. No effect of the PDE4BY358C mutation was observed in the pre-pulse inhibition and forced swim tests. Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.All authors are members of the EUCID.net network, funded by COST (BM1208). TE is funded by the German Ministry of research and education (01GM1513B). GPdN is funded by I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09), Instituto de Salud Carlos III (PI13/00467) and Basque Department of Health (GV2014/111017).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13148-015-0143-