Human pigmentation genes under environmental selection

Genome-wide association studies and comparative genomics have established major loci and specific polymorphisms affecting human skin, hair and eye color. Environmental changes have had an impact on selected pigmentation genes as populations have expanded into different regions of the globe

Infrared Spectroscopy of the Diffuse Ionized Halo of NGC 891

We present infrared spectroscopy from the Spitzer Space Telescope at one disk position and two positions at a height of 1 kpc from the disk in the edge-on spiral NGC 891, with the primary goal of studying halo ionization. Our main result is that the [Ne III]/[Ne II] ratio, which provides a measure of the hardness of the ionizing spectrum free from the major problems plaguing optical line ratios, is enhanced in the extraplanar pointings relative to the disk pointing. Using a 2D Monte Carlo-based photo-ionization code which accounts for the effects of radiation field hardening, we find that this trend cannot be reproduced by any plausible photo-ionization model, and that a secondary source of ionization must therefore operate in gaseous halos. We also present the first spectroscopic detections of extraplanar PAH features in an external normal galaxy. If they are in an exponential layer, very rough emission scale-heights of 330-530 pc are implied for the various features. Extinction may be non-negligible in the midplane and reduce these scale-heights significantly. There is little significant variation in the relative emission from the various features between disk and extraplanar environment. Only the 17.4 micron feature is significantly enhanced in the extraplanar gas compared to the other features, possibly indicating a preference for larger PAHs in the halo.Comment: 35 pages in ApJ preprint format, 8 figures, accepted for publication in ApJ. Minor change to Introduction to give appropriate credit to earlier, related wor

Using real-time data to test for political budget cycles

We use real‐time annual data on the fiscal balance, government current spending, current revenues and net capital outlays as published at a half yearly frequency in the OECD Economic Outlook for 25 OECD countries. For each fiscal year t we have a number of forecasts, a first release, and subsequent revisions. It turns out that revisions in the fiscal balance data are not affected by elections. However, we do find that governments spend more than reported before an election which provides support for moralhazard type of political budget cycle (PBC) models: through hidden efforts the incumbent tries to enhance his perceived competence. We also find that governments had higher current receipts than reported before an election, which is in line with adverse‐selection type of PBC models in which incumbents signal competence through expansionary fiscal policy before the elections

Frontiers in Pigment Cell and Melanoma Research

We identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution

Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells

The melanocortin-1 receptor (MCIR) is a G-protein-coupled receptor expressed primarily in melanocytes and is known to play a pivotal role in the regulation of pigmentation in mammals. In humans MC1R has been found to be highly polymorphic with several functional variants associated with the phenotype of red hair color and fair skin, cutaneous UV sensitivity, and increased risk of developing melanoma and non-melanoma skin cancer. Recent evidence suggests that MC1R plays a photo-protective role in melanocytes in response to UV irradiation. Relatively few genetic targets of MC1R signaling have been identified independent of the pigmentation pathway. Here we show that MC1R signaling in B16 mouse melanoma cells and primary human melanocytes rapidly, and transiently, induces the transcription of the NR4A subfamily of orphan nuclear receptors. Furthermore, primary human melanocytes harboring homozygous RHC variant MC1R alleles exhibited an impaired induction of NR4A genes in response to the potent MC1R agonist (Nle4,D-Phe7)-α-melanocyte-stimulating hormone. Using small interference RNA-mediated attenuation of NR4A1 and NR4A2 expression in melanocytes, the ability to remove cyclobutane pyrimidine dimers following UV irradiation appeared to be impaired in the context of MC1R signaling. These data identify the NR4A receptor family as potential mediators of an MC1R-coordinated DNA damage response to UV exposure in melanocytic cells

BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus

IMPORTANCE The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting

BRAFV600E Mutation Status of Involuting and Stable Nevi in Dabrafenib Therapy with or without Trametinib

IMPORTANCE Recent advances in targeting BRAF(V600E) mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes

Probing the Substellar Regime with SIRTF

One of the main scientific drivers of the Space InfraRed Telescope Facility (SIRTF) is the search for brown dwarfs and extrasolar superplanets. We discuss observational strategies for identification of these objects, and conclude that an optimal strategy is a wide IRAC survey (18 deg$^2$) with a 5 $\sigma$ sensitivity of 3.9 $\mu$Jy in channel 2 (M$\sim19.1^m$). For this sensitivity, we provide estimates of the number of low mass brown dwarfs and isolated planets detected per square degree for power-law mass functions with $\alpha$=1.5, and 1.0. Shallower surveys covering a larger area are inefficient because of large overheads and detector noise. Deeper surveys covering a smaller area become more and more affected by crowding with galaxies. A survey like the one that we propose would determine the field mass function down to a few Jupiter masses through the identification of a large sample of brown dwarfs and isolated planets. The proposed SIRTF survey would also allow the first detection of ultracool substellar objects with temperatures between 700 K and 200 K. The cooling curves of substellar objects with masses less than 20 Jupiters imply that they should spend most of their lifetimes at temperatures below 700 K. Preliminary models indicate that their atmospheres could be dominated by water clouds, which would diminish their optical and near-infrared fluxes. The properties of those objects are still completely unexplored.Comment: 7 pages, 6 figures, submitted to PAS