The Hubble Constant from Observations of the Brightest Red Giant Stars in a Virgo-Cluster Galaxy

The Virgo and Fornax clusters of galaxies play central roles in determining the Hubble constant H_0. A powerful and direct way of establishing distances for elliptical galaxies is to use the luminosities of the brightest red-giant stars (the TRGB luminosity, at M_I = -4.2). Here we report the direct observation of the TRGB stars in a dwarf elliptical galaxy in the Virgo cluster. We find its distance to be 15.7 +- 1.5 Megaparsecs, from which we estimate a Hubble constant of H_0 = 77 +- 8 km/s/Mpc. Under the assumption of a low-density Universe with the simplest cosmology, the age of the Universe is no more than 12-13 billion years.Comment: 12 pages, LaTeX, with 2 postscript figures; in press for Nature, July 199

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria

<p>Abstract</p> <p>Background</p> <p>In the ICU, bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. However, we still do not know to what extent the magnitude of PCT elevation at the onset of bacteremia varies according to the Gram stain result.</p> <p>Methods</p> <p>Review of the medical records of every patient treated between May, 2004 and December, 2006 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT dosage at the onset of infection was available.</p> <p>Results</p> <p>97 episodes of either GN bacteremia (<it>n </it>= 52) or GP bacteremia (<it>n </it>= 45) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia, whereas the SOFA score value in the two groups was similar. Moreover, in the study population, a high PCT value was found to be independently associated with GN bacteremia. A PCT level of 16.0 ng/mL yielded an 83.0% positive predictive value and a 74.0% negative predictive value for GN-related bacteremia in the study cohort (AUROCC = 0.79; 95% CI, 0.71–0.88).</p> <p>Conclusion</p> <p>In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease.</p

Vascular permeability, vascular hyperpermeability and angiogenesis

The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability

Temporal-spatial profiling of pedunculopontine galanin-cholinergic neurons in the lactacystin rat model of Parkinson’s disease

Parkinson’s disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates a multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor- and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, whilst being upregulated in degenerating brain regions associated with cognitive decline. Here we determined the temporal-spatial profile of progressive expression of endogenous galanin within degenerating cholinergic neurons, across the rostro-caudal axis of the PPN, by utilising the lactacystin-induced rat model of PD. First, we show progressive neuronal death affecting nigral dopaminergic and PPN cholinergic neurons, reflecting that seen in PD patients, to facilitate use of this model for assessing the therapeutic potential of bioactive peptides. Next, stereological analyses of the lesioned brain hemisphere found that the number of PPN cholinergic neurons expressing galanin increased by 11%, compared to sham-lesioned controls, increasing by a further 5% as the neurodegenerative process evolved. Galanin upregulation within cholinergic PPN neurons was most prevalent closest to the intra-nigral lesion site, suggesting that galanin upregulation in such neurons adapt intrinsically to neurodegeneration, to possibly neuroprotect. This is the first report on the extent and pattern of galanin expression in cholinergic neurons across distinct PPN subregions in both the intact rat CNS and lactacystin lesioned rats. The findings pave the way for future work to target galanin signaling in the PPN, to determine the extent to which upregulated galanin expression could offer a viable treatment strategy for ameliorating PD symptoms associated with cholinergic degeneration

The over-representation of binary DNA tracts in seven sequenced chromosomes

BACKGROUND: DNA tracts composed of only two bases are possible in six combinations: A+G (purines, R), C+T (pyrimidines, Y), G+T (Keto, K), A+C (Imino, M), A+T (Weak, W) and G+C (Strong, S). It is long known that all-pyrimidine tracts, complemented by all-purines tracts ("R.Y tracts"), are excessively present in analyzed DNA. We have previously shown that R.Y tracts are in vast excess in yeast promoters, and brought evidence for their role in gene regulation. Here we report the systematic mapping of all six binary combinations on the level of complete sequenced chromosomes, as well as in their different subregions. RESULTS: DNA tracts composed of the above binary base combinations have been mapped in seven sequenced chromosomes: Human chromosomes 21 and 22 (the major contigs); Drosophila melanogaster chr. 2R; Caenorhabditis elegans chr. I; Arabidopsis thaliana chr. II; Saccharomyces cerevisiae chr. IV and M. jannaschii. A huge over-representation, reaching million-folds, has been found for very long tracts of all binary motifs except S, in each of the seven organisms. Long R.Y tracts are the most excessive, except in D. melanogaster, where the K.M motif predominates. S (G, C rich) tracts are in excess mainly in CpG islands; the W motif predominates in bacteria. Many excessively long W tracts are nevertheless found also in the archeon and in the eukaryotes. The survey of complete chromosomes enables us, for the first time, to map systematically the intergenic regions. In human and other chromosomes we find the highest over-representation of the binary DNA tracts in the intergenic regions. These over-representations are only partly explainable by the presence of interspersed elements. CONCLUSIONS: The over-representation of long DNA tracts composed of five of the above motifs is the largest deviation from randomness so far established for DNA, and this in a wide range of eukaryotic and archeal chromosomes. A propensity for ready DNA unwinding is proposed as the functional role, explaining the evolutionary conservation of the huge excesses observed

Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages

Streptococcus uberis is frequently isolated from the mammary gland of dairy cattle. Infection with some strains can induce mild subclinical inflammation whilst others induce severe inflammation and clinical mastitis. We compared here the inflammatory response of primary cultures of bovine mammary epithelial cells (pbMEC) towards S. uberis strains collected from clinical or subclinical cases (seven strains each) of mastitis with the strong response elicited by Escherichia coli. Neither heat inactivated nor live S. uberis induced the expression of 10 key immune genes (including TNF, IL1B, IL6). The widely used virulent strain 0140J and the avirulent strain, EF20 elicited similar responses; as did mutants defective in capsule (hasA) or biofilm formation (sub0538 and sub0539). Streptococcus uberis failed to activate NF-κB in pbMEC or TLR2 in HEK293 cells, indicating that S. uberis particles did not induce any TLR-signaling in MEC. However, preparations of lipoteichoic acid (LTA) from two strains strongly induced immune gene expression and activated NF-κB in pbMEC, without the involvement of TLR2. The immune-stimulatory LTA must be arranged in the intact S. uberis such that it is unrecognizable by the relevant pathogen receptors of the MEC. The absence of immune recognition is specific for MEC, since the same S. uberis preparations strongly induced immune gene expression and NF-κB activity in the murine macrophage model cell RAW264.7. Hence, the sluggish immune response of MEC and not of professional immune cells to this pathogen may aid establishment of the often encountered belated and subclinical phenotype of S. uberis mastitis