A methodology for estimating dog noise in an animal housing facility

A rectangular reverberation chamber was designed, constructed and calibrated for the experimental measurement of the sound power level (acoustic power) of a dog. Calibration of the chamber consisted of comparing the acoustic power measured for a random noise source in the chamber with that for the identical source in a free field environment. Data from dogs indicate that barking noise can be modeled as a square wave pattern with short duration and peak sound power levels in the 500 Hz octave band. A-weighted sound pressure levels of up to 114.7 dBA were absorbed, indicating a potential concern for both animals and man chronically exposed to such environments

Control of nuclear-cytoplasmic shuttling of Ankrd54 by PKCδ

AIM To identify and characterize the effect of phosphorylation on the subcellular localization of Ankrd54. METHODS HEK293T cells were treated with calyculin A, staurosporin or phorbol 12-myristate 13-acetate (PMA). Cells were transfected with eGFP-tagged Ankrd54 with or without Lyn tyrosine kinase (wild-type, Y397F mutant, or Y508F mutant). The subcellular localization was assessed by immunofluorescence imaging of cells, immunoblotting of subcellular fractionations. The phosphorylation of Ankrd54 was monitored using Phos-tagTM gel retardation. Phosphorylated peptides were analysed by multiple-reaction-monitoring (MRM) proteomic analysis. RESULTS Activation of PKC kinases using PMA promoted nuclear export of Ankrd54 and correlated with increased Ankrd54 phosphorylation, assayed using Phos-tagTM gel retardation. Co-expression of an active form of the PKCδ isoform specifically promoted both phosphorylation and cytoplasmic localization of Ankrd54, while PKCδ, Akt and PKA did not. Alanine mutation of several serine residues in the amino-terminal region of Ankrd54 (Ser14, Ser17, Ser18, Ser19) reduced both PMA induced cytoplasmic localization and phosphorylation of Ankrd54. Using MRM proteomic analysis, phosphorylation of the Ser18 residue of Ankrd54 was readily detectable in response to PMA stimulation. PMA stimulation of cells co-expressing Ankrd54 and Lyn tyrosine kinase displayed increased co-immunoprecipitation and enhanced co-localization in the cytoplasm. CONCLUSION We identify phosphorylation by PKCδ as a major regulator of nuclear-cytoplasmic shuttling of Ankrd54, and its interaction with the tyrosine kinase Lyn

Author Correction: Identification of a novel cAMP dependent protein kinase A phosphorylation site on the human cardiac calcium channel

The original version of this Article contained a typographical error in the spelling of the author A. Harvey Millar, which was incorrectly given as Harvey A. Millar. This has now been corrected in the PDF and HTML versions of the Article and in the Supplementary Information

Current approaches to management of bone sarcoma in adolescent and young adult patients

Bone tumors are a group of histologically diverse diseases that occur across all ages. Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic adolescent and young adult (AYA) cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met

Behavioral Responses of a Parasitoid Fly to Rapidly Evolving Host Signals

Animals eavesdrop on signals and cues generated by prey, predators, hosts, parasites, competing species, and conspecifics, and the conspicuousness of sexual signals makes them particularly susceptible. Yet, when sexual signals evolve, most attention is paid to impacts on intended receivers (potential mates) rather than fitness consequences for eavesdroppers. Using the rapidly evolving interaction between the Pacific field cricket, Teleogryllus oceanicus, and the parasitoid fly, Ormia ochracea, we asked how parasitoids initially respond to novel changes in host signals. We recently discovered a novel sexual signal, purring song, in Hawaiian populations of T. oceanicus that appears to have evolved because it protects the cricket from the parasitoid while still allowing males to attract female crickets for mating. In Hawaii, there are no known alternative hosts for the parasitoid, so we would expect flies to be under selection to detect and attend to the new purring song. We used complementary field and laboratory phonotaxis experiments to test fly responses to purring songs that varied in many dimensions, as well as to ancestral song. We found that flies strongly prefer ancestral song over purring songs in both the field and the lab, but we caught more flies to purring songs in the field than reported in previous work, indicating that flies may be exerting some selective pressure on the novel song. When played at realistic amplitudes, we found no preferences–flies responded equally to all purrs that varied in frequency, broadbandedness, and temporal measures. However, our lab experiment did reveal the first evidence of preference for purring song amplitude, as flies were more attracted to purrs played at amplitudes greater than naturally occurring purring songs. As purring becomes more common throughout Hawaii, flies that can use purring song to locate hosts should be favored by selection and increase in frequency

SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages

Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages

Health-Related Quality of Life and Experiences of Sarcoma Patients during the COVID-19 Pandemic

Sarcomas are rare cancers with a spectrum of clinical needs and outcomes. We investigated care experiences and health-related quality of life (HRQoL) in sarcoma patients during the COVID-19 pandemic. Patients with appointments during the first two months of the UK lockdown were invited to complete a survey. Questions included views on care modifications, COVID-19 worry and psychosocial impact, and EORTC-QLQ-C30 items. 350 patients completed the survey; median age 58 (16–92) years. Care modifications included telemedicine (74%) and postponement of appointments (34%), scans (34%) or treatment (10%). Most felt the quality of care was not affected (72%), however, social life (87%) and emotional wellbeing (41%) were affected. Worry about COVID-19 infection was moderately high (mean 5.8/10) and significantly related to higher cancer-related worry; associated with lower emotional functioning irrespective of treatment intent. Curative patients (44%) with low resilient coping scores had significantly higher COVID-19 worry. Patients who did not know their treatment intent (22%) had significantly higher COVID-19 worry and insomnia. In summary, care experiences were generally positive; however, cancer-related worry, low resilient coping and uncertainty about treatment intent were associated with COVID-19 worry. These patients may benefit from additional psychological support during the pandemic and beyond

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

First upper limits from LIGO on gravitational wave bursts

We report on a search for gravitational wave bursts using data from the first science run of the LIGO detectors. Our search focuses on bursts with durations ranging from 4 ms to 100 ms, and with significant power in the LIGO sensitivity band of 150 to 3000 Hz. We bound the rate for such detected bursts at less than 1.6 events per day at 90% confidence level. This result is interpreted in terms of the detection efficiency for ad hoc waveforms (Gaussians and sine-Gaussians) as a function of their root-sum-square strain h_{rss}; typical sensitivities lie in the range h_{rss} ~ 10^{-19} - 10^{-17} strain/rtHz, depending on waveform. We discuss improvements in the search method that will be applied to future science data from LIGO and other gravitational wave detectors.Comment: 21 pages, 15 figures, accepted by Phys Rev D. Fixed a few small typos and updated a few reference