Using Narrow Band Photometry to Detect Young Brown Dwarfs in IC348

We report the discovery of a population of young brown dwarf candidates in the open star cluster IC348 and the development of a new spectroscopic classification technique using narrow band photometry. Observations were made using FLITECAM, the First Light Camera for SOFIA, at the 3-m Shane Telescope at Lick Observatory. FLITECAM is a new 1-5 micron camera with an 8 arcmin field of view. Custom narrow band filters were developed to detect absorption features of water vapor (at 1.495 microns) and methane (at 1.66 microns) characteristic of brown dwarfs. These filters enable spectral classification of stars and brown dwarfs without spectroscopy. FLITECAM's narrow and broadband photometry was verified by examining the color-color and color-magnitude characteristics of stars whose spectral type and reddening was known from previous surveys. Using our narrow band filter photometry method, it was possible to identify an object measured with a signal-to-noise ratio of 20 or better to within +/-3 spectral class subtypes for late-type stars. With this technique, very deep images of the central region of IC348 (H ~ 20.0) have identified 18 sources as possible L or T dwarf candidates. Out of these 18, we expect that between 3 - 6 of these objects are statistically likely to be background stars, with the remainder being true low-mass members of the cluster. If confirmed as cluster members then these are very low-mass objects (~5 Mjupiter). We also describe how two additional narrow band filters can improve the contrast between M, L, and T dwarfs as well as provide a means to determine the reddening of an individual object.Comment: 43 pages, 17 figures. Accepted for publication in the Astrophysical Journal 27 June 200

Patterns of Resource Use by a Drosophilid (Diptera) Leaf Miner on a Native Crucifer

Distribution and damage of Scaptomyza nigrita Wheeler on its host (bittercress, Cardamine cordifolia A. Gray), a native perennial crucifer, were examined over two growing seasons in relation to leaf position. Concentrations of defensive compounds (glucosinolates) and of nutritive compounds (total nitrogen, free amino acids, soluble carbohydrates) were also examined. The fly-host plant relationship was studied in sun and shade habitats at two sites. Oviposition and leaf-mining damage were concentrated on the lower central leaves of a stem in both habitats. These mature leaves have lower glucosinolate concentrations than new leaves. Adult densities and larval feeding damage were consistently and significantly greater on plants in the sun than on those in the shade. Higher S. nigrita densities in the sun habitat and slightly higher soluble carbohydrate concentrations in sun leaves at the beginning of the growing season, rather than variation in defensive glucosinolate levels, are the most likely mechanisms determining higher levels of leaf mining on host plants in the sun habitat

\u3ci\u3eScaptomyza nigrita\u3c/i\u3e Wheeler (Diptera: Drosophilidae), a Leaf Miner of the Native Crucifer, \u3ci\u3eCardamine cordifolia\u3c/i\u3e A. Gray (Bittercress)

The biology of Scaptomyza nigrita on its host plant, a native crucifer (Bittercress) in the Rocky Mountains, is described. Development of each stage in the life history was studied both in the field and in the laboratory. This is the first documentation of a host for S. nigrita. We examined the activity of adult flies in two adjacent habitats, sun and adjacent willow shade. Adult flies were more abundant on bittercress plants in sun-exposed versus in shaded areas, and were most active from mid-day to late afternoon. Female flies were significantly larger than male flies, but there were no differences in size of adults between the two habitats. Larval damage to bittercress is generally much greater on plants in sunny areas than on those in the shade, possibly due to the increased activity of ovipositing flies in sun-exposed areas

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

An extended XMM-Newton observation of the Seyfert galaxy NGC 4051. II. Soft X-ray emission from a limb-brightened shell of post-shock gas

An extended XMM-Newton observation of the Seyfert I galaxy NGC 4051 in 2009 revealed a complex absorption spectrum, with a wide range of outflow velocities and ionisation states.The main velocity and ionisation structure was interpreted in Paper I in terms of a decelerating, recombining flow resulting from the shocking of a still higher velocity wind colliding with the ISM or slower moving ejecta. The high sensitivity of the XMM-Newton observation also revealed a number of broad emission lines, all showing evidence of self-absorption near the line cores. The line profiles are found here to be consistent with emission from a limb-brightened shell of post-shock gas building up ahead of the contact discontinuity. While the broad emission lines remain quasi-constant as the continuum flux changes by an order of magnitude, recombination continua of several H- and He-like ions are found to vary in response to the continuum, providing an important key to scaling the ionised flow.Comment: Accepted for publication in MNRA

Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized

Shadoo (Sprn) and prion disease incubation time in mice

Prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease (vCJD). The prion protein (PrP) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. Other genes are also thought to be important and a plausible candidate is Sprn, which encodes the PrP-like protein Shadoo (Sho). Sho is expressed in the adult central nervous system and exhibits neuroprotective activity reminiscent of PrP in an in vitro assay. To investigate the role of Sprn in prion disease incubation time we sequenced the open reading frame (ORF) in a diverse panel of mice and saw little variation except in strains derived from wild-trapped mice. Sequencing the untranslated regions revealed polymorphisms that allowed us to carry out an association study of incubation period in the Northport heterogeneous stock of mice inoculated with Chandler/RML prions. We also examined the expression level of Sprn mRNA in the brains of normal and prion-infected mice and saw no correlation with either genotype or incubation time. We therefore conclude that Sprn does not play a major role in prion disease incubation time in these strains of mice

Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

OBJECTIVE: To use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside. METHODS: Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008-December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility. RESULTS: The Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated. CONCLUSIONS: These two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up

T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade

Engagement of the β2 integrin, lymphocyte function-associated antigen-1 (LFA-1), results in stabilization of T cell mRNA transcripts containing AU-rich elements (AREs) by inducing rapid nuclear-to-cytosolic translocation of the RNA-stabilizing protein, HuR. However, little is known regarding integrin-induced signaling cascades that affect mRNA catabolism. This study examines the role of the GTPases, Rac 1 and Rac 2, and their downstream effectors, in the LFA-1-induced effects on mRNA.Engagement of LFA-1 to its ligand, ICAM-1, in human peripheral T cells resulted in rapid activation of Rac1 and Rac2. siRNA-mediated knockdown of either Rac1 or Rac2 prevented LFA-1-stimulated stabilization of the labile transcripts encoding IFN-γ and TNF-α, and integrin mediated IFN-γ mRNA stabilization was absent in T cells obtained from Rac2 gene-deleted mice. LFA-1 engagement-induced translocation of HuR and stabilization of TNF- α mRNA was lost in Jurkat cells deficient in the Rac guanine nucleotide exchange factor Vav-1 (J.Vav1). The transfection of J.Vav1 cells with constitutively active Rac1 or Rac2 stabilized a labile β-globin reporter mRNA, in a HuR-dependent manner. Furthermore, LFA-1-mediated mRNA stabilization and HuR translocation in mouse splenic T cells was dependent on the phosphorylation of the mitogen-activated protein kinase kinase, MKK3, and its target MAP kinase p38MAPK, and lost in T cells obtained from MKK3 gene-deleted mice.Collectively, these results demonstrate that LFA-1-induced stabilization of ARE-containing mRNAs in T cells is dependent on HuR, and occurs through the Vav-1, Rac1/2, MKK3 and p38MAPK signaling cascade. This pathway constitutes a molecular switch that enhances immune and pro-inflammatory gene expression in T cells undergoing adhesion at sites of activation and effector function

HECTD2 Is Associated with Susceptibility to Mouse and Human Prion Disease

Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods