The Discovery of Sgr A*

The compact radio source Sgr A* is associated with a 3.6 million black hole at the center of the Milky Way. The radio source was discovered in February 1974 by Bruce Balick and Robert L.Brown. The National Radio Astronomy Observatory's Green Bank 35 km radio link interferometer was used. We discuss other observations in the years 1965-1985 as well as early VLBI observations. The name Sgr A* was used for the first time in 1982 by Robert L.Brown and has become the accepted name in the intervening years.Comment: 8 pages,2 figures. Conference proceedings: "The central 300 parsecs of the Milky Way", editors A.Cotera, H.Falcke, T.R.Geballe, S.Markof

Rayleigh-Taylor Instabilities in Type Ia Supernova Remnants undergoing Cosmic-Ray Particle Acceleration - Low Adiabatic Index Solutions

This study investigates the evolution of Rayleigh-Taylor (R-T) instabilities in Type Ia supernova remnants that are associated with a low adiabatic index gamma, where gamma < 5/3, which reflects the expected change in the supernova shock structure as a result of cosmic-ray particle acceleration. Extreme cases, such as the case with the maximum compression ratio that corresponds to gamma=1.1, are examined. As gamma decreases, the shock compression ratio rises, and an increasingly narrow inter shock region with a more pronounced initial mixture of R-T unstable gas is produced. Consequently, the remnant outline may be perturbed by small-amplitude, small-wavelength bumps. However, as the instability decays over time, the extent of convective mixing in terms of the ratio of the radius of the R-T fingers to the blast wave does not strongly depend on the value of gamma for gamma >= 1.2. As a result of the age of the remnant, the unstable gas cannot extend sufficiently far to form metal-enriched filaments of ejecta material close to the periphery of Tycho's supernova remnant. The consistency of the dynamic properties of Tycho's remnant with the adiabatic model gamma=5/3 reveals that the injection of cosmic rays is too weak to alter the shock structure. Even with very efficient acceleration of cosmic rays at the shock, significantly enhanced mixing is not expected in Type Ia supernova remnants.Comment: 11 pages, 10 figures, MNRAS, accepte

Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer's disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome-mitochondria crosstalk and in neuron-glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications

Anticipated regret to increase uptake of colorectal cancer screening (ARTICS):a randomised controlled trial

Objective. Screening is key to early detection of colorectal cancer. Our aim was to determine whether a simple anticipated regret (AR) intervention could increase colorectal cancer screening uptake. Methods. We conducted a randomised controlled trial of a simple, questionnaire-based AR intervention, delivered alongside existing pre-notification letters. 60,000 adults aged 50-74 from the Scottish National Screening programme were randomised to: 1) no questionnaire (control), 2) Health Locus of Control questionnaire (HLOC) or 3) HLOC plus anticipated regret questionnaire (AR). Primary outcome was guaiac Faecal Occult Blood Test (FOBT) return. Secondary outcomes included intention to return test kit and perceived disgust (ICK). Results. 59,366 people were analysed as allocated (Intentionto- treat (ITT)); there were no overall differences between treatment groups on FOBT uptake (control: 57.3%, HLOC: 56.9%, AR: 57.4%). 13,645 (34.2%) people returned questionnaires. Analysis of the secondary questionnaire measures showed that AR had an indirect effect on FOBT uptake via intention, whilst ICK had a direct effect on FOBT uptake over and above intention. The effect of AR on FOBT uptake was also moderated by intention strength: for less than strong intenders only, uptake was 4.2% higher in the AR (84.6%) versus the HLOC group (80.4%) (95% CI for difference (2.0, 6.5)). Conclusion. The findings show that psychological concepts including anticipated regret and perceived disgust (ICK) are important factors in determining FOBT uptake. However, there was no simple effect of the AR intervention in the ITT. We conclude that exposure to AR in those with low intentions may be required to increase FOBT uptake. Current controlled trials: www.controlledtrials. com number: ISRCTN74986452

Comparative transcriptomic analysis of Porphyromonas gingivalis biofilm and planktonic cells

<p>Abstract</p> <p>Background</p> <p><it>Porphyromonas gingivalis </it>in subgingival dental plaque, as part of a mature biofilm, has been strongly implicated in the onset and progression of chronic periodontitis. In this study using DNA microarray we compared the global gene expression of a <it>P. gingivalis </it>biofilm with that of its planktonic counterpart grown in the same continuous culture.</p> <p>Results</p> <p>Approximately 18% (377 genes, at 1.5 fold or more, <it>P</it>-value < 0.01) of the <it>P. gingivalis </it>genome was differentially expressed when the bacterium was grown as a biofilm. Genes that were down-regulated in biofilm cells, relative to planktonic cells, included those involved in cell envelope biogenesis, DNA replication, energy production and biosynthesis of cofactors, prosthetic groups and carriers. A number of genes encoding transport and binding proteins were up-regulated in <it>P. gingivalis </it>biofilm cells. Several genes predicted to encode proteins involved in signal transduction and transcriptional regulation were differentially regulated and may be important in the regulation of biofilm growth.</p> <p>Conclusion</p> <p>This study analyzing global gene expression provides insight into the adaptive response of <it>P. gingivalis </it>to biofilm growth, in particular showing a down regulation of genes involved in growth and metabolic activity.</p

High Energy Cosmic Rays From Supernovae

Cosmic rays are charged relativistic particles that reach the Earth with extremely high energies, providing striking evidence of the existence of effective accelerators in the Universe. Below an energy around $\sim 10^{17}$ eV cosmic rays are believed to be produced in the Milky Way while above that energy their origin is probably extragalactic. In the early '30s supernovae were already identified as possible sources for the Galactic component of cosmic rays. After the '70s this idea has gained more and more credibility thanks to the the development of the diffusive shock acceleration theory, which provides a robust theoretical framework for particle energization in astrophysical environments. Afterwards, mostly in recent years, much observational evidence has been gathered in support of this framework, converting a speculative idea in a real paradigm. In this Chapter the basic pillars of this paradigm will be illustrated. This includes the acceleration mechanism, the non linear effects produced by accelerated particles onto the shock dynamics needed to reach the highest energies, the escape process from the sources and the transportation of cosmic rays through the Galaxy. The theoretical picture will be corroborated by discussing several observations which support the idea that supernova remnants are effective cosmic ray factories.Comment: Final draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdi

Jet-lag in Sgr A*: What size and timing measurements tell us about the central black hole in the Milky Way

The black hole at the Galactic Center, Sgr A*, is the prototype of a galactic nucleus at a very low level of activity. Its radio through submm-wave emission is known to come from a region close to the event horizon, however, the source of the emission is still under debate. A successful theory explaining the emission is based on a relativistic jet model scaled down from powerful quasars. We want to test the predictive power of this established jet model against newly available measurements of wavelength-dependent time lags and the size-wavelength structure in Sgr A*. Using all available closure amplitude VLBI data from different groups, we again derived the intrinsic wavelength-dependent size of Sgr A*. This allowed us to calculate the expected frequency-dependent time lags of radio flares, assuming a range of in- and outflow velocities. Moreover, we calculated the time lags expected in the previously published pressure-driven jet model. The predicted lags are then compared to radio monitoring observations at 22, 43, and 350 GHz. The combination of time lags and size measurements imply a mildly relativistic outflow with bulk outflow speeds of gamma*beta ~ 0.5-2. The newly measured time lags are reproduced well by the jet model without any major fine tuning. The results further strengthen the case for the cm-to-mm wave radio emission in Sgr A* as coming from a mildly relativistic jet-like outflow. The combination of radio time lag and VLBI closure amplitude measurements is a powerful new tool for assessing the flow speed and direction in Sgr A*. Future VLBI and time lag measurements over a range of wavelengths will reveal more information about Sgr A*, such as the existence of a jet nozzle, and measure the detailed velocity structure of a relativistic jet near its launching point for the first time.Comment: Latex, 7 pages, accepted for publication in Astronomy & Astrophysic

Is expression of p120ctn in oral squamous cell carcinomas a prognostic factor?

Objectives p120ctn is a component of the catenin family. To date, there have only been two studies examining expression levels of p120ctn in oral squamous cell carcinoma (OSCC). Materials and methods Paraffined specimens of 113 OSCCs and 12 of normal mucosa were examined by immunohistochemistry. Frozen samples of 20 OSCCs and 5 of normal mucosa were examined by Western blot (WB). Results were correlated with clinicopathological parameters. Five cell lines were examined by immunofluorescence, immunocytochemistry, and WB to show immunoreactivity and cellular localization of p120ctn. Results Altered p120ctn expression was observed in 109/113 cases of OSCC. Heterogenous cytoplasmic/nuclear expression was associated with loss of membranous distribution (88/113 cases). Complete loss of expression was noted in 21/113 cases. Increased cytoplasmic expression was evident in all positive cases, without significant correlation among p120ctn staining/pattern and grading/stage. Reduction/absence of p120ctn expression was related to poor prognosis ( P Conclusion p120ctn delocalization/loss of expression could be an independent prognostic marker in OSCC

Bacterial membrane vesicles transport their DNA cargo into host cells

© 2017 The Author(s). Bacterial outer membrane vesicles (OMVs) are extracellular sacs containing biologically active products, such as proteins, cell wall components and toxins. OMVs are reported to contain DNA, however, little is known about the nature of this DNA, nor whether it can be transported into host cells. Our work demonstrates that chromosomal DNA is packaged into OMVs shed by bacteria during exponential phase. Most of this DNA was present on the external surfaces of OMVs, with smaller amounts located internally. The DNA within the internal compartments of Pseudomonas aeruginosa OMVs were consistently enriched in specific regions of the bacterial chromosome, encoding proteins involved in virulence, stress response, antibiotic resistance and metabolism. Furthermore, we demonstrated that OMVs carry DNA into eukaryotic cells, and this DNA was detectable by PCR in the nuclear fraction of cells. These findings suggest a role for OMV-associated DNA in bacterial-host cell interactions and have implications for OMV-based vaccines

Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

Metastasis is the main cause of cancer-related death and thus understanding the molecular and cellular mechanisms underlying this process is critical. Here, our data demonstrate, contrary to established dogma, that loss of haematopoietic-derived focal adhesion kinase (FAK) is sufficient to enhance tumour metastasis. Using both experimental and spontaneous metastasis models, we show that genetic ablation of haematopoietic FAK does not affect primary tumour growth but enhances the incidence of metastasis significantly. At a molecular level, haematopoietic FAK deletion results in an increase in PU-1 levels and decrease in GATA-1 levels causing a shift of hematopoietic homeostasis towards a myeloid commitment. The subsequent increase in circulating granulocyte number, with an increase in serum CXCL12 and granulocyte CXCR4 levels, was required for augmented metastasis in mice lacking haematopoietic FAK. Overall our findings provide a mechanism by which haematopoietic FAK controls cancer metastasis