294 research outputs found

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

    Get PDF
    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

    Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes

    Get PDF
    Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15), a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populations and sensitised larvae to the xenotoxin silver nitrate. Although pericardial nephrocytes in dKlf15 loss of function mutants were specified during embryogenesis, they failed to express the slit diaphragm gene sticks and stones and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led to reduced surface expression of the endocytic receptor Amnionless and loss of in vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers and rescued age-dependent decline in nephrocyte function. The data place dKlf15 upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway and suggest dKlf15 expression is both necessary and sufficient to sustain nephrocyte differentiation. These findings explain the physiological relevance of dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is evolutionarily conserve

    Uptake of the Necrotic Serpin in Drosophila melanogaster via the Lipophorin Receptor-1

    Get PDF
    The humoral response to fungal and Gram-positive infections is regulated by the serpin-family inhibitor, Necrotic. Following immune-challenge, a proteolytic cascade is activated which signals through the Toll receptor. Toll activation results in a range of antibiotic peptides being synthesised in the fat-body and exported to the haemolymph. As with mammalian serpins, Necrotic turnover in Drosophila is rapid. This serpin is synthesised in the fat-body, but its site of degradation has been unclear. By “freezing” endocytosis with a temperature sensitive Dynamin mutation, we demonstrate that Necrotic is removed from the haemolymph in two groups of giant cells: the garland and pericardial athrocytes. Necrotic uptake responds rapidly to infection, being visibly increased after 30 mins and peaking at 6–8 hours. Co-localisation of anti-Nec with anti-AP50, Rab5, and Rab7 antibodies establishes that the serpin is processed through multi-vesicular bodies and delivered to the lysosome, where it co-localises with the ubiquitin-binding protein, HRS. Nec does not co-localise with Rab11, indicating that the serpin is not re-exported from athrocytes. Instead, mutations which block late endosome/lysosome fusion (dor, hk, and car) cause accumulation of Necrotic-positive endosomes, even in the absence of infection. Knockdown of the 6 Drosophila orthologues of the mammalian LDL receptor family with dsRNA identifies LpR1 as an enhancer of the immune response. Uptake of Necrotic from the haemolymph is blocked by a chromosomal deletion of LpR1. In conclusion, we identify the cells and the receptor molecule responsible for the uptake and degradation of the Necrotic serpin in Drosophila melanogaster. The scavenging of serpin/proteinase complexes may be a critical step in the regulation of proteolytic cascades

    Evolution of Competitive Ability: An Adaptation Speed vs. Accuracy Tradeoff Rooted in Gene Network Size

    Get PDF
    Ecologists have increasingly come to understand that evolutionary change on short time-scales can alter ecological dynamics (and vice-versa), and this idea is being incorporated into community ecology research programs. Previous research has suggested that the size and topology of the gene network underlying a quantitative trait should constrain or facilitate adaptation and thereby alter population dynamics. Here, I consider a scenario in which two species with different genetic architectures compete and evolve in fluctuating environments. An important trade-off emerges between adaptive accuracy and adaptive speed, driven by the size of the gene network underlying the ecologically-critical trait and the rate of environmental change. Smaller, scale-free networks confer a competitive advantage in rapidly-changing environments, but larger networks permit increased adaptive accuracy when environmental change is sufficiently slow to allow a species time to adapt. As the differences in network characteristics increase, the time-to-resolution of competition decreases. These results augment and refine previous conclusions about the ecological implications of the genetic architecture of quantitative traits, emphasizing a role of adaptive accuracy. Along with previous work, in particular that considering the role of gene network connectivity, these results provide a set of expectations for what we may observe as the field of ecological genomics develops

    Smaller Gene Networks Permit Longer Persistence in Fast-Changing Environments

    Get PDF
    The environments in which organisms live and reproduce are rarely static, and as the environment changes, populations must evolve so that phenotypes match the challenges presented. The quantitative traits that map to environmental variables are underlain by hundreds or thousands of interacting genes whose allele frequencies and epistatic relationships must change appropriately for adaptation to occur. Extending an earlier model in which individuals possess an ecologically-critical trait encoded by gene networks of 16 to 256 genes and random or scale-free topology, I test the hypothesis that smaller, scale-free networks permit longer persistence times in a constantly-changing environment. Genetic architecture interacting with the rate of environmental change accounts for 78% of the variance in trait heritability and 66% of the variance in population persistence times. When the rate of environmental change is high, the relationship between network size and heritability is apparent, with smaller and scale-free networks conferring a distinct advantage for persistence time. However, when the rate of environmental change is very slow, the relationship between network size and heritability disappears and populations persist the duration of the simulations, without regard to genetic architecture. These results provide a link between genes and population dynamics that may be tested as the -omics and bioinformatics fields mature, and as we are able to determine the genetic basis of ecologically-relevant quantitative traits

    Functional Comparison of Innate Immune Signaling Pathways in Primates

    Get PDF
    Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host–virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases

    Effects of Data Quality Vetoes on a Search for Compact Binary Coalescences in Advanced LIGO's First Observing Run

    Get PDF
    The first observing run of Advanced LIGO spanned 4 months, from September 12, 2015 to January 19, 2016, during which gravitational waves were directly detected from two binary black hole systems, namely GW150914 and GW151226. Confident detection of gravitational waves requires an understanding of instrumental transients and artifacts that can reduce the sensitivity of a search. Studies of the quality of the detector data yield insights into the cause of instrumental artifacts and data quality vetoes specific to a search are produced to mitigate the effects of problematic data. In this paper, the systematic removal of noisy data from analysis time is shown to improve the sensitivity of searches for compact binary coalescences. The output of the PyCBC pipeline, which is a python-based code package used to search for gravitational wave signals from compact binary coalescences, is used as a metric for improvement. GW150914 was a loud enough signal that removing noisy data did not improve its significance. However, the removal of data with excess noise decreased the false alarm rate of GW151226 by more than two orders of magnitude, from 1 in 770 years to less than 1 in 186000 years.Comment: 27 pages, 13 figures, published versio
    corecore