The Lack of Torus Emission from BL Lacertae Objects: An Infrared View of Unification with WISE

We use data from the Wide-Field Infrared Survey Explorer (WISE) to perform a statistical study on the mid-infrared (IR) properties of a large number ($\sim10^2$) of BL Lac objects --- low-luminosity Active Galactic Nuclei (AGN) with a jet beamed toward the Earth. As expected, many BL Lac objects are so highly beamed that their jet synchrotron emission dominates their IR spectral energy distributions. In other BL Lac objects, however, the jet is not strong enough to completely dilute the rest of the AGN emission. We do not see observational signatures of the dusty torus from these weakly beamed BL Lac objects. The lack of observable torus emission is consistent with suggestions that BL Lac objects are fed by radiatively inefficient accretion disks. Implications for the "nature vs. nurture" debate for FR I and FR II radio galaxies are briefly discussed. Our study supports the notion that, beyond orientation, accretion rate plays an important role in AGN unification.Comment: 6 Pages, 3 Figures, accepted for publication in ApJ Letter

Mutant huntingtin enhances activation of dendritic Kv4 K+ channels in striatal spiny projection neurons

Huntington\u27s disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued by knocking-down expression of Kv4 channels, by disrupting KChIP binding, by restoring TrkB receptor signaling or by lowering mutant-Htt (mHtt) levels with a zinc finger protein. Collectively, these studies demonstrate that mHtt induces reversible alterations in the dendritic excitability of iSPNs that could contribute to the motor symptoms of HD

Explicit factorization of external coordinates in constrained Statistical Mechanics models

If a macromolecule is described by curvilinear coordinates or rigid constraints are imposed, the equilibrium probability density that must be sampled in Monte Carlo simulations includes the determinants of different mass-metric tensors. In this work, we explicitly write the determinant of the mass-metric tensor G and of the reduced mass-metric tensor g, for any molecule, general internal coordinates and arbitrary constraints, as a product of two functions; one depending only on the external coordinates that describe the overall translation and rotation of the system, and the other only on the internal coordinates. This work extends previous results in the literature, proving with full generality that one may integrate out the external coordinates and perform Monte Carlo simulations in the internal conformational space of macromolecules. In addition, we give a general mathematical argument showing that the factorization is a consequence of the symmetries of the metric tensors involved. Finally, the determinant of the mass-metric tensor G is computed explicitly in a set of curvilinear coordinates specially well-suited for general branched molecules.Comment: 22 pages, 2 figures, LaTeX, AMSTeX. v2: Introduccion slightly extended. Version in arXiv is slightly larger than the published on

The colours of BL Lac objects: a new approach to their classification

We selected a sample of 437 BL Lac objects, taken from the RomaBZCat catalogue, for which spectroscopic information and SDSS photometry is available. We propose a new classification of BL Lacs in which the sources' type is not defined only on the basis of the peak frequency of the synchrotron component in their Spectral Energy Distribution (types L and H), but also on the relevance of this component with respect to the brightness of the host galaxy (types N and G, for nuclear or galaxy dominated sources). We found that the SDSS colour index u-r=1.4 is a good separator between these two types. We used multiband colour-colour plots to study the properties of the BL Lac classes and found that in the X-ray to radio flux ratio vs u-r plot most of the N (blue) sources are located in a rather narrow strip, while the G-sources (red) are spread in a large area, and most of them are located in galaxy clusters or interacting systems, suggesting that their X-ray emission is not from a genuine BL Lac nucleus but it is related to their environment. Of the about 135 sources detected in the gamma-rays by Fermi-GST, nearly all belong to the N-type, indicating that only this type of sources should be considered as genuine BL Lac nuclei. The J-H, H-K plot of sources detected in the 2MASS catalogue is consistent with that of the "bona fide" BL Lac objects, independently of their N or G classification from the optical indices, indicating the existence in G-type sources of a K-band excess possibly due to a steep, low frequency peaked emission which deserves further investigations. We propose to use these colour plots as a further tool for searching candidate counterparts of newly discovered high-energy sources.Comment: 11 pages, 7 figures. Submitted 29/08/2011 to MNRAS, first referee report received 31/10/2011, accepted 21/02/201

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Environmental shaping of codon usage and functional adaptation across microbial communities.

Microbial communities represent the largest portion of the Earth's biomass. Metagenomics projects use high-throughput sequencing to survey these communities and shed light on genetic capabilities that enable microbes to inhabit every corner of the biosphere. Metagenome studies are generally based on (i) classifying and ranking functions of identified genes; and (ii) estimating the phyletic distribution of constituent microbial species. To understand microbial communities at the systems level, it is necessary to extend these studies beyond the species' boundaries and capture higher levels of metabolic complexity. We evaluated 11 metagenome samples and demonstrated that microbes inhabiting the same ecological niche share common preferences for synonymous codons, regardless of their phylogeny. By exploring concepts of translational optimization through codon usage adaptation, we demonstrated that community-wide bias in codon usage can be used as a prediction tool for lifestyle-specific genes across the entire microbial community, effectively considering microbial communities as meta-genomes. These findings set up a 'functional metagenomics' platform for the identification of genes relevant for adaptations of entire microbial communities to environments. Our results provide valuable arguments in defining the concept of microbial species through the context of their interactions within the community

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

Age-Correlated Gene Expression in Normal and Neurodegenerative Human Brain Tissues

Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer's disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles.We have developed a computational method for assessing an individual's "physiological brain age" by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases--Alzheimer's disease (AD, superior frontal gyrus), frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex ∼BA10)--showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles.This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases