158 research outputs found

    Towards a best practice for the use of active non-contact surface scanning to record human skeletal remains from archaeological contexts

    Get PDF
    Active surface scanners emit light or a laser stripe to record the exterior surface of an object or landscape, providing results in three dimensions. The use of active surface scanners to record anthropological and archaeological contexts has increased within the last few years, creating a number of sub-contexts within these disciplines, and allowing a further development of certain applications, such as quantitative analysis, the use of replicas in education and museums, and the creation of digital databases archived in institutions. However with guidance, this paper aims to assess the advantages and disadvantages of active surface scanning and the potential for research with regards to the recording and analysis of human skeletal remains. The key advantages and uses identified include: quantitative digitisation, geometric morphometric studies, conservation, preservation, documentation, and reconstruction. However, surface scanning also has some limitations, including: cost, technological expertise, the need for a power source, computing requirements, and data size. Overall, the application of active surface scanning technology to archaeological skeletal remains will provide a vital digital archive that will serve to preserve the integrity of this fragile and finite resource for future generations. This is particularly important within the current developer-funded environment in which many skeletal collections, including those yielding unique or unusual pathological or morphological features, are re-buried, with only very limited time for analysis

    APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

    Get PDF
    p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5–6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53–DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter–luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury

    Mapping the Dark Matter From UV Light at High Redshift: An Empirical Approach to Understand Galaxy Statistics

    Full text link
    We present a simple formalism to interpret two galaxy statistics, the UV luminosity function and two-point correlation functions for star-forming galaxies at z~4, 5, 6 in the context of LCDM cosmology. Both statistics are the result of how star formation takes place in DM halos, and thus are used to constrain how UV light depends on halo properties such as mass. The two measures were taken from the GOODS data, thus ideal for joint analysis. The two physical quantities we explore are the SF duty cycle, and the range of L_UV that a halo of mass M can have (mean and variance). The former addresses the typical duration of SF activity in halos while the latter addresses the averaged SF history and regularity of gas inflow into these systems. We explore various physical models consistent with data, and find the following: 1) the typical duration of SF observed in the data is <0.4 Gyr (1 sig), 2) the inferred scaling law between L_UV and halo mass M from the observed slope of the LFs is roughly linear at all redshifts, and 3) L_UV for a fixed halo mass decreases with time, implying that the SF efficiency (after dust extinction) is higher at earlier times. We explore several physical scenarios relating star formation to halo mass, but find that these scenarios are indistinguishable due to the limited range of halo mass probed by our data. In order to discriminate between different scenarios, we discuss constraining the bright-faint galaxy cross-correlation functions and luminosity-dependence of galaxy bias. (Abridged)Comment: 24 pages, 16 figures: matches published version -- Astrophysical Journal 695 (2009) 368-39

    A Novel Molecular Solution for Ultraviolet Light Detection in Caenorhabditis elegans

    Get PDF
    For many organisms the ability to transduce light into cellular signals is crucial for survival. Light stimulates DNA repair and metabolism changes in bacteria, avoidance responses in single-cell organisms, attraction responses in plants, and both visual and nonvisual perception in animals. Despite these widely differing responses, in all of nature there are only six known families of proteins that can transduce light. Although the roundworm Caenorhabditis elegans has none of the known light transduction systems, we show here that C. elegans strongly accelerates its locomotion in response to blue or shorter wavelengths of light, with maximal responsiveness to ultraviolet light. Our data suggest that C. elegans uses this light response to escape the lethal doses of sunlight that permeate its habitat. Short-wavelength light drives locomotion by bypassing two critical signals, cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), that neurons use to shape and control behaviors. C. elegans mutants lacking these signals are paralyzed and unresponsive to harsh physical stimuli in ambient light, but short-wavelength light rapidly rescues their paralysis and restores normal levels of coordinated locomotion. This light response is mediated by LITE-1, a novel ultraviolet light receptor that acts in neurons and is a member of the invertebrate Gustatory receptor (Gr) family. Heterologous expression of the receptor in muscle cells is sufficient to confer light responsiveness on cells that are normally unresponsive to light. Our results reveal a novel molecular solution for ultraviolet light detection and an unusual sensory modality in C. elegans that is unlike any previously described light response in any organism

    TESSA: A toolkit for rapid assessment of ecosystem services at sites of biodiversity conservation importance

    Get PDF
    Sites that are important for biodiversity conservation can also provide significant benefits (i.e. ecosystem services) to people. Decision-makers need to know how change to a site, whether development or restoration, would affect the delivery of services and the distribution of any benefits among stakeholders. However, there are relatively few empirical studies that present this information. One reason is the lack of appropriate methods and tools for ecosystem service assessment that do not require substantial resources or specialist technical knowledge, or rely heavily upon existing data. Here we address this gap by describing the Toolkit for Ecosystem Service Site-based Assessment (TESSA). It guides local non-specialists through a selection of relatively accessible methods for identifying which ecosystem services may be important at a site, and for evaluating the magnitude of benefits that people obtain from them currently, compared with those expected under alternative land-uses. The toolkit recommends use of existing data where appropriate and places emphasis on enabling users to collect new field data at relatively low cost and effort. By using TESSA, the users could also gain valuable information about the alternative land-uses; and data collected in the field could be incorporated into regular monitoring programmes

    Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

    Get PDF
    We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

    Desmoglein-2 is Important for Islet Function and β-Cell Survival

    Get PDF
    Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal that DSG2 is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In a Dsg2 loss-of-function mice (Dsg

    Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

    Get PDF
    Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

    Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Get PDF
    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases
    • …
    corecore