CIRPASS near-infrared integral-field spectroscopy of massive star clusters in the starburst galaxy NGC 1140

[ABRIDGED] We analyse near-infrared integral field spectroscopy of the central starburst region of NGC 1140, obtained at the Gemini-South telescope equipped with CIRPASS. Our ~1.45-1.67 um wavelength coverage includes the bright [Fe II] emission line, as well as high-order Brackett (hydrogen) lines. While strong [Fe II] emission, thought to originate in the thermal shocks associated with supernova remnants, is found throughout the galaxy, both Br 12-4 and Br 14-4 emission, and weak CO(6,3) absorption, is predominantly associated with the northern starburst region. The Brackett lines originate from recombination processes occurring on smaller scales in (young) HII regions. The time-scale associated with strong [Fe II] emission implies that most of the recent star-formation activity in NGC 1140 was induced in the past 35-55 Myr. Based on the spatial distributions of the [Fe II] versus Brackett line emission, we conclude that a galaxy-wide starburst was induced several tens of Myr ago, with more recent starburst activity concentrated around the northern starburst region. This scenario is (provisionally) confirmed by our analysis of the spectral energy distributions of the compact, young massive star clusters (YMCs) detected in new and archival broad-band HST images. The YMC ages in NGC 1140 are all <= 20 Myr, consistent with independently determined estimates of the galaxy's starburst age, while there appears to be an age difference between the northern and southern YMC complexes in the sense expected from our CIRPASS analysis. Our photometric mass estimates of the NGC 1140 YMCs, likely upper limits, are comparable to those of the highest-mass Galactic globular clusters and to spectroscopically confirmed masses of (compact) YMCs in other starburst galaxies.Comment: 16 pages LaTeX, incl. 6 postscript figures; accepted for publication in MNRA

Malignant Precursor Cells Pre-Exist in Human Breast DCIS and Require Autophagy for Survival

BACKGROUND: While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells. We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells. Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2-4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft. We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells. The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from the organ culture, and abrogated xenograft tumor formation. CONCLUSIONS: Cytogenetically abnormal spheroid forming, tumorigenic, and invasive neoplastic epithelial cells pre-exist in human DCIS and require cellular autophagy for survival

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

SNLS Spectroscopy: Testing for Evolution in Type Ia Supernovae

Aims: We present a quantitative study of a new data set of high redshift Type Ia supernovae spectra, observed at the Gemini telescopes during the first 34 months of the Supernova Legacy Survey. During this time 123 supernovae candidates were observed, of which 87 have been identified as SNe Ia at a median redshift of z=0.720. Spectra from the entire second year of the survey and part of the third year (59 total SNe candidates with 46 confirmed SNe Ia) are published here for the first time. The spectroscopic measurements made on this data set are used determine if these distant SNe comprise a population similar to those observed locally. Methods: Rest-frame equivalent width and ejection velocity measurements are made on four spectroscopic features. Corresponding measurements are presented for a set of 167 spectra from 24 low-z SNe Ia from the literature. Results: We show that there exists a sample at high redshift with properties similar to nearby SNe. No significant difference was found between the distributions of measurements at low and high redsift for three of the features. The fourth feature displays a possible difference that should be investigated further. Correlations between Type Ia SNe properties and host galaxy morphology were also found to be similar at low and high z, and within each host galaxy class we see no evidence for redshift-evolution in SN properties. A new correlation between SNe Ia peak magnitude and the equivalent width of SiII absorption is presented. We demonstrate that this correlation reduces the scatter in SNe Ia luminosity distances in a manner consistent with the lightcurve shape-luminosity corrections that are used for Type Ia SNe cosmology. Conclusions: We show that this new sample of SNLS SNe Ia has spectroscopic properties similar to nearby objects. (Abridged)Comment: Accepted for publication in Astronomy and Astrophysic

The [OII]/Halpha ratio of emission line galaxies in the 2dF redshift survey

We investigate the systematic variation of the [OII]3727/Halpha flux line ratio as a function of various galaxy properties, i.e., luminosity, metallicity, reddening, and excitation state, for a sample of 1124 emission-line galaxies, with a mean redshift z ~ 0.06, drawn from the Two Degree Field Galaxy Redshift Survey. The mean observed and extinction-corrected emission-line flux ratios agree well with the values derived from the $B$-band selected Nearby Field Galaxy Survey galaxy sample, but are significantly different from the values obtained from the Halpha-selected Universidad Complutense de Madrid Survey galaxy sample. This is because the different selection criteria applied in these surveys lead to a significant difference in the mean extinction and metallicity of different samples. We use the R_{23} parameter to estimate the gas-phase oxygen abundance and find that the extinction-corrected [OII]3727/Halpha ratio depends on the oxygen abundance. For 12+log(O/H)>8.4, we confirm that the emission-line ratio decreases with increasing metallicity. We have extended the relationship further to the metal-poor regime, 12+log(O/H)< 8.4, and find that the correlation between the extinction-corrected [OII]3727/Halpha ratio and the metallicity reverses in comparison to the relationship for metal-rich galaxies. For metal-poor galaxies, in contrast with metal-rich ones, the variation of extinction-corrected [OII]3727/Halpha ratio is correlated with the ionization states of the interstellar gas.Comment: 2005, MNRAS 362, 1143 (16 pages, 16 figures

Melancholic versus non-melancholic depression: differences on cognitive function. A longitudinal study protocol

<p>Abstract</p> <p>Background</p> <p>Cognitive dysfunction is common among depressed patients. However, the pattern and magnitude of impairment during episodes of major depressive disorder (MDD) through to clinical remission remains unclear. Heterogeneity of depressive patients and the lack of longitudinal studies may account for contradictory results in previous research.</p> <p>Methods/Design</p> <p>This longitudinal study will analyze cognitive differences between CORE-defined melancholic depressed patients (n = 60) and non-melancholic depressed patients (n = 60). A comprehensive clinical and cognitive assessment will be performed at admission and after 6 months. Cognitive dysfunction in both groups will be longitudinally compared, and the persistence of cognitive impairment after clinical remission will be determined.</p> <p>Discussion</p> <p>The study of neuropsychological dysfunction and the cognitive changes through the different phases of depression arise a wide variety of difficulties. Several confounding variables must be controlled to determine if the presence of depression could be considered the only factor accounting for group differences.</p

Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.</p> <p>Methods</p> <p>CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals.</p> <p>Results</p> <p>The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: <it>CYP3A4*1B</it>, 4.8 % (95% C.I. 2.6–7.0), 3.7 % (0.8–6.6) 4.3% (2.0–6.6) and 4.3% (2.1–6.5); <it>CYP3A5*3</it>, 91.8 % (93.0–97.4), 95.7% (92.6–98.8), 91.7% (88.6–94.8) and 90.8% (87.7–93.9). The association between <it>CYP3A4*1B </it>and <it>CYP3A5*3 </it>variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage.</p> <p>Conclusion</p> <p>Common polymorphisms on <it>CYP3A4 </it>and <it>CYP3A5 </it>genes do not modify the risk of developing digestive cancers in Western Europe.</p

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case–control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case–control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses

Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology.

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented

Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the methylation of CpG islands within the DNA and the modification of amino acids in the N-terminal histone tails. In the last years, it became evident that the onset of cancer and its progression may not occur only due to genetic mutations but also because of changes in the patterns of epigenetic modifications. In contrast to genetic mutations, which are almost impossible to reverse, epigenetic changes are potentially reversible. This implies that they are amenable to pharmacological interventions. Therefore, a lot of work in recent years has focussed on the development of small molecule enzyme inhibitors like DNA-methyltransferase inhibitors or inhibitors of histone-modifying enzymes. These may reverse misregulated epigenetic states and be implemented in the treatment of cancer or other diseases, e.g., neurological disorders. Today, several epigenetic drugs are already approved by the FDA and the EMEA for cancer treatment and around ten histone deacetylase (HDAC) inhibitors are in clinical development. This review will give an update on recent clinical trials of the HDAC inhibitors used systemically that were reported in 2009 and 2010 and will present an overview of different biomarkers to monitor the biological effects