Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity

Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase–deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy

A massive cluster of Red Supergiants at the base of the Scutum-Crux arm

We report on the unprecedented Red Supergiant (RSG) population of a massive young cluster, located at the base of the Scutum-Crux Galactic arm. We identify candidate cluster RSGs based on {\it 2MASS} photometry and medium resolution spectroscopy. With follow-up high-resolution spectroscopy, we use CO-bandhead equivalent width and high-precision radial velocity measurements to identify a core grouping of 26 physically-associated RSGs -- the largest such cluster known to-date. Using the stars' velocity dispersion, and their inferred luminosities in conjuction with evolutionary models, we argue that the cluster has an initial mass of $\sim$40,000\msun, and is therefore among the most massive in the galaxy. Further, the cluster is only a few hundred parsecs away from the cluster of 14 RSGs recently reported by Figer et al (2006). These two RSG clusters represent 20% of all known RSGs in the Galaxy, and now offer the unique opportunity to study the pre-supernova evolution of massive stars, and the Blue- to Red-Supergiant ratio at uniform metallicity. We use GLIMPSE, MIPSGAL and MAGPIS survey data to identify several objects in the field of the larger cluster which seem to be indicative of recent region-wide starburst activity at the point where the Scutum-Crux arm intercepts the Galactic bulge. Future abundance studies of these clusters will therefore permit the study of the chemical evolution and metallicity gradient of the Galaxy in the region where the disk meets the bulge.Comment: 49 pages, 22 figures. Accepted for publication in ApJ. Version with hi-res figures can be found at http://www.cis.rit.edu/~bxdpci/RSGC2.pd

The cool supergiant population of the massive young star cluster RSGC1

We present new high-resolution near-IR spectroscopy and OH maser observations to investigate the population of cool luminous stars of the young massive Galactic cluster RSGC1. Using the 2.293\micron CO-bandhead feature, we make high-precision radial velocity measurements of 16 of the 17 candidate Red Supergiants (RSGs) identified by Figer et al. We show that F16 and F17 are foreground stars, while we confirm that the rest are indeed physically-associated RSGs. We determine that Star F15, also associated with the cluster, is a Yellow Hypergiant based on its luminosity and spectroscopic similarity to $\rho$ Cas. Using the cluster's radial velocity, we have derived the kinematic distance to the cluster and revisited the stars' temperatures and luminosities. We find a larger spread of luminosities than in the discovery paper, consistent with a cluster age 30% older than previously thought (12$\pm$2Myr), and a total initial mass of $(3\pm1) \times 10^{4}$\msun. The spatial coincidence of the OH maser with F13, combined with similar radial velocities, is compelling evidence that the two are related. Combining our results with recent SiO and H$_2$O maser observations, we find that those stars with maser emission are the most luminous in the cluster. From this we suggest that the maser-active phase is associated with the end of the RSG stage, when the luminosity-mass ratios are at their highest.Comment: 31 pages, 11 figures. Accepted for publication in Ap

Future perspectives in melanoma research: meeting report from the “Melanoma Bridge”, Napoli, December 5th-8th 2013

The fourth “Melanoma Bridge Meeting” took place in Naples, December 5 to 8th, 2013. The four topics discussed at this meeting were: Diagnosis and New Procedures, Molecular Advances and Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent research in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors, like BRAF and MEK inhibitors, as well as other signaling pathways inhibitors, are being tested in metastatic melanoma either as monotherapy or in combination, and have yielded promising results. Improved survival rates have also been observed with immune therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in melanoma as well. This meeting’s specific focus was on advances in targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. Significant consideration was given to issues surrounding the development of novel therapeutic targets as further study of patterns of resistance to both immunologic and targeted drugs are paramount to future drug development to guide existing and future therapies. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma

Epigenetic Silencing of Spermatocyte-Specific and Neuronal Genes by SUMO Modification of the Transcription Factor Sp3

SUMO modification of transcription factors is linked to repression of transcription. The physiological significance of SUMO attachment to a particular transcriptional regulator, however, is largely unknown. We have employed the ubiquitously expressed murine transcription factor Sp3 to analyze the role of SUMOylation in vivo. We generated mice and mouse embryonic fibroblasts (MEFs) carrying a subtle point mutation in the SUMO attachment sequence of Sp3 (IKEE553D mutation). The E553D mutation impedes SUMOylation of Sp3 at K551 in vivo, without affecting Sp3 protein levels. Expression profiling revealed that spermatocyte-specific genes, such as Dmc1 and Dnahc8, and neuronal genes, including Paqr6, Rims3, and Robo3, are de-repressed in non-testicular and extra-neuronal mouse tissues and in mouse embryonic fibroblasts expressing the SUMOylation-deficient Sp3E553D mutant protein. Chromatin immunoprecipitation experiments show that transcriptional de-repression of these genes is accompanied by the loss of repressive heterochromatic marks such as H3K9 and H4K20 tri-methylation and impaired recruitment of repressive chromatin-modifying enzymes. Finally, analysis of the DNA methylation state of the Dmc1, Paqr6, and Rims3 promoters by bisulfite sequencing revealed that these genes are highly methylated in Sp3wt MEFs but are unmethylated in Sp3E553D MEFs linking SUMOylation of Sp3 to tissue-specific CpG methylation. Our results establish SUMO conjugation to Sp3 as a molecular beacon for the assembly of repression machineries to maintain tissue-specific transcriptional gene silencing

Comparable Ages for the Independent Origins of Electrogenesis in African and South American Weakly Electric Fishes

One of the most remarkable examples of convergent evolution among vertebrates is illustrated by the independent origins of an active electric sense in South American and African weakly electric fishes, the Gymnotiformes and Mormyroidea, respectively. These groups independently evolved similar complex systems for object localization and communication via the generation and reception of weak electric fields. While good estimates of divergence times are critical to understanding the temporal context for the evolution and diversification of these two groups, their respective ages have been difficult to estimate due to the absence of an informative fossil record, use of strict molecular clock models in previous studies, and/or incomplete taxonomic sampling. Here, we examine the timing of the origins of the Gymnotiformes and the Mormyroidea using complete mitogenome sequences and a parametric Bayesian method for divergence time reconstruction. Under two different fossil-based calibration methods, we estimated similar ages for the independent origins of the Mormyroidea and Gymnotiformes. Our absolute estimates for the origins of these groups either slightly postdate, or just predate, the final separation of Africa and South America by continental drift. The most recent common ancestor of the Mormyroidea and Gymnotiformes was found to be a non-electrogenic basal teleost living more than 85 millions years earlier. For both electric fish lineages, we also estimated similar intervals (16–19 or 22–26 million years, depending on calibration method) between the appearance of electroreception and the origin of myogenic electric organs, providing rough upper estimates for the time periods during which these complex electric organs evolved de novo from skeletal muscle precursors. The fact that the Gymnotiformes and Mormyroidea are of similar age enhances the comparative value of the weakly electric fish system for investigating pathways to evolutionary novelty, as well as the influences of key innovations in communication on the process of species radiation

A phylogenetic classification of the world’s tropical forests

Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition and dynamics. Such understanding will enable anticipation of region specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present the first classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (1) Indo-Pacific, (2) Subtropical, (3) African, (4) American, and (5) Dry forests. Our results do not support the traditional Neo- versus Palaeo-tropical forest division, but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar and India. Additionally, a northern hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern hemisphere forests