992 research outputs found

    Laterobasal aculear serrations (LAS) in scorpion family Vaejovidae (Scorpiones: Chactoidea)

    Get PDF
    The discovery of a new structure on the laterobasal aspect of the telson aculeus is described here for the first time. This structure, termed the laterobasal aculear serrations (LAS), is a row of minute denticles located on each side of the aculeus base, found exclusively in scorpion family Vaejovidae, thus potentially providing a new synapomorphy for this New World family. The LAS structure of major representative vaejovid genera and Vaejovis groups is illustrated with SEM micrographs. Also provided is a comprehensive list of non-vaejovid Recent scorpion genera examined where the LAS structure was found to be absent

    TOXIFY: a deep learning approach to classify animal venom proteins

    Get PDF
    In the era of Next-Generation Sequencing and shotgun proteomics, the sequences of animal toxigenic proteins are being generated at rates exceeding the pace of traditional means for empirical toxicity verification. To facilitate the automation of toxin identification from protein sequences, we trained Recurrent Neural Networks with Gated Recurrent Units on publicly available datasets. The resulting models are available via the novel software package TOXIFY, allowing users to infer the probability of a given protein sequence being a venom protein. TOXIFY is more than 20X faster and uses over an order of magnitude less memory than previously published methods. Additionally, TOXIFY is more accurate, precise, and sensitive at classifying venom proteins

    Applications of neuroimaging to disease-modification trials in Alzheimer's disease.

    Get PDF
    Critical to development of new therapies for Alzheimer's disease (AD) is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD

    Involvement of a putative intercellular signal-recognizing G protein-coupled receptor in the engulfment of Salmonella by the protozoan Tetrahymena

    Get PDF
    In an effort to investigate the molecular basis of protozoa engulfment-mediated hypervirulence of Salmonella in cattle, we evaluated protozoan G protein-coupled receptors (GPCRs) as transducers of Salmonella engulfment by the model protozoanTetrahymena. Our laboratory previously demonstrated that non-pathogenic protozoa (including Tetrahymena) engulf Salmonella and then exacerbate its virulence in cattle, but the mechanistic details of the phenomenon are not fully understood. GPCRs were investigated since these receptors facilitate phagocytosis of particulates byTetrahymena, and a GPCR apparently modulates bacterial engulfment for the pathogenic protozoan Entamoeba histolytica. A database search identified three putative Tetrahymena GPCRs, based on sequence homologies and predicted transmembrane domains, that were the focus of this study. Salmonella engulfment by Tetrahymenawas assessed in the presence of suramin, a non-specific GPCR inhibitor. Salmonella engulfment was also assessed in Tetrahymena in which expression of putative GPCRs was knocked-down using RNAi. A candidate GPCR was then expressed in a heterologous yeast expression system for further characterization. Our results revealed that Tetrahymena were less efficient at engulfing Salmonella in the presence of suramin. Engulfment was reduced concordantly with a reduction in the density of protozoa. RNAi-based studies revealed that knock-down of one the Tetrahymena GPCRs caused diminished engulfment of Salmonella. Tetrahymena lysates activated this receptor in the heterologous expression system. These data demonstrate that the Tetrahymena receptor is a putative GPCR that facilitates bacterial engulfment by Tetrahymena. Activation of the putative GPCR seemed to be related to protozoan cell density, suggesting that its cognate ligand is an intercellular signaling molecule

    The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

    Get PDF
    To gain further knowledge on the preclinical phase of AD, we sought to characterize cognitive performance, volumetric MRI, amyloid PET, FDG PET, retinal amyloid, and plasma biomarkers in a cohort of non-demented adults with Down Syndrome (DS). The goal of the Down Syndrome Biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30-60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid PET 18F-florbetapir, 18F-fluorodeoxyglucose (18F-FDG) PET, and retinal amyloid imaging. In addition, plasma beta-amyloid species were measured and ApoE genotyping was performed. Consistent with previous autopsy studies, subjects demonstrated amyloid PET positivity reflecting fibrillar amyloid plaque deposition. Results from our multimodal analysis also suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Retinal amyloid imaging demonstrated presence of plaques. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971

    The White Dwarf Cooling Sequence of NGC6397

    Get PDF
    We present the results of a deep Hubble Space Telescope (HST) exposure of the nearby globular cluster NGC6397, focussing attention on the cluster's white dwarf cooling sequence. This sequence is shown to extend over 5 magnitudes in depth, with an apparent cutoff at magnitude F814W=27.6. We demonstrate, using both artificial star tests and the detectability of background galaxies at fainter magnitudes, that the cutoff is real and represents the truncation of the white dwarf luminosity function in this cluster. We perform a detailed comparison between cooling models and the observed distribution of white dwarfs in colour and magnitude, taking into account uncertainties in distance, extinction, white dwarf mass, progenitor lifetimes, binarity and cooling model uncertainties. After marginalising over these variables, we obtain values for the cluster distance modulus and age of \mu_0 = 12.02 \pm 0.06 and T_c = 11.47 \pm 0.47Gyr (95% confidence limits). Our inferred distance and white dwarf initial-final mass relations are in good agreement with other independent determinations, and the cluster age is consistent with, but more precise than, prior determinations made using the main sequence turnoff method. In particular, within the context of the currently accepted \Lambda CDM cosmological model, this age places the formation of NGC6397 at a redshift z=3, at a time when the cosmological star formation rate was approaching its peak.Comment: 56 pages, 30 figure

    The Space Motion of the Globular Cluster NGC 6397

    Get PDF
    As a by-product of high-precision, ultra-deep stellar photometry in the Galactic globular cluster NGC 6397 with the Hubble Space Telescope, we are able to measure a large population of background galaxies whose images are nearly point-like. These provide an extragalactic reference frame of unprecedented accuracy, relative to which we measure the most accurate absolute proper motion ever determined for a globular cluster. We find mu_alpha = 3.56 +/- 0.04 mas/yr and mu_delta = -17.34 +/- 0.04 mas/yr. We note that the formal statistical errors quoted for the proper motion of NGC 6397 do not include possible unavoidable sources of systematic errors, such as cluster rotation. These are very unlikely to exceed a few percent. We use this new proper motion to calculate NGC 6397's UVW space velocity and its orbit around the Milky Way, and find that the cluster has made frequent passages through the Galactic disk.Comment: 5 pages including 3 figures, accepted for publication in the Astrophysical Journal Letters. Very minor changes in V2. typos fixe

    Shifting Evolutionary Sands: Transcriptome Characterization of the Aptostichus Atomarius Species Complex

    Get PDF
    Abstract Background Mygalomorph spiders represent a diverse, yet understudied lineage for which genomic level data has only recently become accessible through high-throughput genomic and transcriptomic sequencing methods. The Aptostichus atomarius species complex (family Euctenizidae) includes two coastal dune endemic members, each with inland sister species – affording exploration of dune adaptation associated patterns at the transcriptomic level. We apply an RNAseq approach to examine gene family conservation across the species complex and test for patterns of positive selection along branches leading to dune endemic species. Results An average of ~ 44,000 contigs were assembled for eight spiders representing dune (n = 2), inland (n = 4), and atomarius species complex outgroup taxa (n = 2). Transcriptomes were estimated to be 64% complete on average with 77 spider reference orthologs missing from all taxa. Over 18,000 orthologous gene clusters were identified within the atomarius complex members, > 5000 were detected in all species, and ~ 4700 were shared between species complex members and outgroup Aptostichus species. Gene family analysis with the FUSTr pipeline identified 47 gene families appearing to be under selection in the atomarius ingroup; four of the five top clusters include sequences strongly resembling other arthropod venom peptides. The COATS pipeline identified six gene clusters under positive selection on branches leading to dune species, three of which reflected the preferred species tree. Genes under selection were identified as Cytochrome P450 2c15 (also recovered in the FUSTr analysis), Niemann 2 Pick C1-like, and Kainate 2 isoform X1. Conclusions We have generated eight draft transcriptomes for a closely related and ecologically diverse group of trapdoor spiders, identifying venom gene families potentially under selection across the Aptostichus atomarius complex and chemosensory-associated gene families under selection in dune endemic lineages

    Child mental health in Jordanian orphanages: effect of placement change on behavior and caregiving

    Get PDF
    Background: To assess the mental health and behavioral problems of children in institutional placements in Jordan to inform understanding of current needs, and to explore the effects of placement change on functioning and staff perceptions of goodness-of-fit. Methods: An assessment was completed of 134 children between 1.5? 12 years-of-age residing in Jordanian orphanages. The Child Behavior Checklist was used to assess prevalence rates of problems across externalizing and internalizing behavior and DSM-IV oriented subscales. Also included was caregiver perceived goodness-of-fit with each child, caregiving behavior, and two placement change-clock variables; an adjustment clock measuring time since last move, and an anticipation clock measuring time to next move. Results: 28% were in the clinical range for the internalizing domain on the CBCL, and 22% for the externalizing domain. The children also exhibited high levels of clinical range social problems, affective disorder, pervasive developmental disorder, and conduct problems. Internalizing problems were found to decrease with time in placement as children adjust to a prior move, whereas externalizing problems increased as the time to their next age-triggered move drew closer, highlighting the anticipatory effects of change. Both behavioral problems and the change clocks were predictive of staff perceptions of goodness-of-fit with the children under their care. Conclusions: These findings add to the evidence demonstrating the negative effects of orphanage rearing, and highlight the importance of the association between behavioral problems and child-caregiver relationship pathways including the timing of placement disruptions and staff perceptions of goodness-of-fit

    The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad-Line Region

    Full text link
    We present models of the Hβ\beta-emitting broad-line region (BLR) in seven Seyfert 1 galaxies from the Lick AGN (Active Galactic Nucleus) Monitoring Project 2011 sample, drawing inferences on the BLR structure and dynamics as well as the mass of the central supermassive black hole. We find that the BLR is generally a thick disk, viewed close to face-on, with preferential emission back toward the ionizing source. The dynamics in our sample range from near-circular elliptical orbits to inflowing or outflowing trajectories. We measure black hole masses of log10(MBH/M)=6.480.18+0.21\log_{10}(M_{\rm BH}/M_\odot) = 6.48^{+0.21}_{-0.18} for PG 1310-108, 7.500.18+0.257.50^{+0.25}_{-0.18} for Mrk 50, 7.460.21+0.157.46^{+0.15}_{-0.21} for Mrk 141, 7.580.08+0.087.58^{+0.08}_{-0.08} for Mrk 279, 7.110.17+0.207.11^{+0.20}_{-0.17} for Mrk 1511, 6.650.15+0.276.65^{+0.27}_{-0.15} for NGC 4593, and 6.940.14+0.146.94^{+0.14}_{-0.14} for Zw 229-015. We use these black hole mass measurements along with cross-correlation time lags and line widths to recover the scale factor ff used in traditional reverberation mapping measurements. Combining our results with other studies that use this modeling technique, bringing our sample size to 16, we calculate a scale factor that can be used for measuring black hole masses in other reverberation mapping campaigns. When using the root-mean-square (rms) spectrum and using the line dispersion to measure the line width, we find log10(frms,σ)pred=0.57±0.19\log_{10}(f_{{\rm rms},\sigma})_{\rm pred} = 0.57 \pm 0.19. Finally, we search for correlations between ff and other AGN and BLR parameters and find marginal evidence that ff is correlated with MBHM_{\rm BH} and the BLR inclination angle, but no significant evidence of a correlation with the AGN luminosity or Eddington ratio.Comment: 26 pages, 14 figures. Accepted for publication in Ap
    corecore