Lifting the Dusty Veil With Near- and Mid-Infrared Photometry: III. Two-Dimensional Extinction Maps of the Galactic Midplane Using the Rayleigh-Jeans Color Excess Method

We provide new, high-resolution A(Ks) extinction maps of the heavily reddened Galactic midplane based on the Rayleigh-Jeans Color Excess ("RJCE") method. RJCE determines star-by-star reddening based on a combination of near- and mid-infrared photometry. The new RJCE-generated maps have 2 x 2 arcmin pixels and span some of the most severely extinguished regions of the Galaxy -- those covered with Spitzer+IRAC imaging by the GLIMPSE-I, -II, -3D, and Vela-Carina surveys, from 256<l<65 deg and, in general, for |b| <= 1-1.5 deg (extending up to |b|<=4 deg in the bulge). Using RJCE extinction measurements, we generate dereddened color-magnitude diagrams and, in turn, create maps based on main sequence, red clump, and red giant star tracers, each probing different distances and thereby providing coarse three-dimensional information on the relative placement of dust cloud structures. The maps generated from red giant stars, which reach to ~18-20 kpc, probe beyond most of the Milky Way extinction in most directions and provide close to a "total Galactic extinction" map -- at minimum they provide high angular resolution maps of lower limits on A(Ks). Because these maps are generated directly from measurements of reddening by the very dust being mapped, rather than inferred on the basis of some less direct means, they are likely the most accurate to date for charting in detail the highly patchy differential extinction in the Galactic midplane. We provide downloadable FITS files and an IDL tool for retrieving extinction values for any line of sight within our mapped regions.Comment: 23 pages, 5 figures, accepted for publication in ApJ

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Primary Somatosensory Cortices Contain Altered Patterns of Regional Cerebral Blood Flow in the Interictal Phase of Migraine

The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique—arterial spin labeling (ASL)—to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks

Galaxy Zoo: Passive Red Spirals

We study the spectroscopic properties and environments of red spiral galaxies found by the Galaxy Zoo project. By carefully selecting face-on, disk dominated spirals we construct a sample of truly passive disks (not dust reddened, nor dominated by old stellar populations in a bulge). As such, our red spirals represent an interesting set of possible transition objects between normal blue spirals and red early types. We use SDSS data to investigate the physical processes which could have turned these objects red without disturbing their morphology. Red spirals prefer intermediate density regimes, however there are no obvious correlations between red spiral properties and environment - environment alone is not sufficient to determine if a spiral will become red. Red spirals are a small fraction of spirals at low masses, but are a significant fraction at large stellar masses - massive galaxies are red independent of morphology. We confirm that red spirals have older stellar popns and less recent star formation than the main spiral population. While the presence of spiral arms suggests that major star formation cannot have ceased long ago, we show that these are not recent post-starbursts, so star formation must have ceased gradually. Intriguingly, red spirals are ~4 times more likely than normal spirals to host optically identified Seyfert or LINER, with most of the difference coming from LINERs. We find a curiously large bar fraction in the red spirals suggesting that the cessation of star formation and bar instabilities are strongly correlated. We conclude by discussing the possible origins. We suggest they may represent the very oldest spiral galaxies which have already used up their reserves of gas - probably aided by strangulation, and perhaps bar instabilities moving material around in the disk.Comment: MNRAS in press, 20 pages, 15 figures (v3

Cortico–Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine

Abstract Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino–vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico–cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N = 40) and matched healthy control subjects (N = 40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition, and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that cortico–cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms

Galaxy Zoo: the dependence of morphology and colour on environment

We analyse the relationships between galaxy morphology, colour, environment and stellar mass using data for over 100,000 objects from Galaxy Zoo, the largest sample of visually classified morphologies yet compiled. We conclusively show that colour and morphology fractions are very different functions of environment. Both are sensitive to stellar mass; however, at fixed stellar mass, while colour is also highly sensitive to environment, morphology displays much weaker environmental trends. Only a small part of both relations can be attributed to variation in the stellar mass function with environment. Galaxies with high stellar masses are mostly red, in all environments and irrespective of their morphology. Low stellar-mass galaxies are mostly blue in low-density environments, but mostly red in high-density environments, again irrespective of their morphology. The colour-density relation is primarily driven by variations in colour fractions at fixed morphology, in particular the fraction of spiral galaxies that have red colours, and especially at low stellar masses. We demonstrate that our red spirals primarily include galaxies with true spiral morphology. We clearly show there is an environmental dependence for colour beyond that for morphology. Before using the Galaxy Zoo morphologies to produce the above results, we first quantify a luminosity-, size- and redshift-dependent classification bias that affects this dataset, and probably most other studies of galaxy population morphology. A correction for this bias is derived and applied to produce a sample of galaxies with reliable morphological type likelihoods, on which we base our analysis.Comment: 25 pages, 20 figures (+ 6 pages, 11 figures in appendices); moderately revised following referee's comments; accepted by MNRA

Calcium/calmodulin inhibition of the Arabidopsis BRASSINOSTEROID-INSENSITIVE 1 receptor kinase provides a possible link between calcium and brassinosteroid signalling

The receptor kinase BRI1 (BRASSINOSTEROID-INSENSITIVE 1) is a key component in BR (brassinosteroid) perception and signal transduction, and has a broad impact on plant growth and development. In the present study, we demonstrate that Arabidopsis CaM (calmodulin) binds to the recombinant cytoplasmic domain of BRI1 in a Ca2+-dependent manner in vitro. In silico analysis predicted binding to Helix E of the BRI1 kinase subdomain VIa and a synthetic peptide based on this sequence interacted with Ca2+/CaM. Co-expression of CaM with the cytoplasmic domain of BRI1 in Escherichia coli strongly reduced autophosphorylation of BRI1, in particular on tyrosine residues, and also reduced the BRI1-mediated transphosphorylation of E. coli proteins on tyrosine, threonine and presumably serine residues. Several isoforms of CaM and CMLs (CaM-like proteins) were more effective (AtCaM6, AtCaM7 and AtCML8, where At is Arabidopsis thaliana) than others (AtCaM2, AtCaM4 and AtCML11) when co-expressed with BRI1 in E. coli. These results establish a novel assay for recombinant BRI1 transphosphorylation activity and collectively uncover a possible new link between Ca2+ and BR signalling

The Oxygen Paradox, the French Paradox, and age-related diseases

open46openDavies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, Henry J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A.Davies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, HENRY J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Purpose: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)–positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2–positive brain metastases. Patients and Methods: Patients had HER-2–positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. Results: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Conclusion: The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2–positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point