207 research outputs found
Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants
Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function.This work was supported by a Wellcome Trust PRF (101835/Z/13/Z) to PJL and RTF to NJM (093964/Z/10/Z), NHSBT and the NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke’s Charitable Trust
Reducing drug related deaths : a pre-implementation assessment of knowledge,barriers and enablers for naloxone distribution through general practice
Peer reviewedPublisher PD
Variation on a Theme: Vibrational Signaling in Caterpillars of the Rose Hook-Tip Moth, Oreto rosea
Abstract Vibrational communication in hook-tip moth caterpillars is thought to be widely used and highly variable across species, but this phenomenon has been experimentally examined in only two species to date. The purpose of this study is to characterize and describe the function of vibrational signaling in a species, Oreta rosea Walker 1855 (Lepidoptera: Drepanidae), that differs morphologically from previously studied species. Caterpillars of this species produce three distinct types of vibrational signals during territorial encounters with conspecifics — mandible drumming, mandible scraping and lateral tremulation. Signals were recorded using a laser-doppler vibrometer and characterized based on temporal and spectral components. Behavioural encounters between a leaf resident and a conspecific intruder were staged to test the hypothesis that signaling functions as a territorial display. Drumming and scraping signals both involve the use of the mandibles, being hit vertically on, or scraped laterally across, the leaf surface. Lateral tremulation involves quick, short, successive lateral movements of the anterior body region that vibrates the entire leaf. Encounters result in residents signaling, with the highest rates observed when intruders make contact with the resident. Residents signal significantly more than intruders and most conflicts are resolved within 10 minutes, with residents winning 91% of trials. The results support the hypothesis that vibrational signals function to advertise leaf occupancy. Signaling is compared between species, and evolutionary origins of vibrational communication in caterpillars are discussed
Recommended from our members
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Tumor-derived extracellular vesicles (TEV) “educate” healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of downregulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy
The Nearby Type Ibn Supernova 2015G: Signatures of Asymmetry and Progenitor Constraints
SN 2015G is the nearest known SN Ibn to date at 23.2 Mpc and it has proven itself a truly remarkable example of this rare subclass. We present the results of an extensive observational campaign including data from radio through ultraviolet wavelengths. SN 2015G was asymmetric, showing late-time nebular lines redshifted by 1000 km/s. It shared many features with the prototypical SN Ibn 2006jc, including extremely strong He I emission lines and a late-time blue pseudocontinuum. The young SN 2015G showed narrow P-Cygni profiles of He I, but never in its evolution did it show any signature of hydrogen - arguing for a dense, ionized, and hydrogen-free circumstellar medium moving outward with a velocity of 1000 km/s and created by relatively recent mass loss from the progenitor star. Ultraviolet through infrared observations show that the fading SN 2015G (which was probably discovered some 20 days post-peak) had a spectral energy distribution that was well described by a simple, single-component blackbody. Archival HST images provide upper limits on the luminosity of SN 2015G's progenitor, while nondetections of any luminous radio afterglow and optical nondetections of outbursts over the past two decades provide constraints upon its mass-loss history
Early-time Ultraviolet and Optical Hubble Space Telescope Spectroscopy of the Type II Supernova 2022wsp
We report early-time ultraviolet (UV) and optical spectroscopy of the young, nearby Type II supernova (SN) 2022wsp obtained by the Hubble Space Telescope (HST)/STIS at about 10 and 20 days after the explosion. The SN 2022wsp UV spectra are compared to those of other well-observed Type II/IIP SNe, including the recently studied Type IIP SN 2021yja. Both SNe exhibit rapid cooling and similar evolution during early phases, indicating a common behavior among SNe II. Radiative-transfer modeling of the spectra of SN 2022wsp with the TARDIS code indicates a steep radial density profile in the outer layer of the ejecta, a solar metallicity, and a relatively high total extinction of E(B - V ) = 0.35 mag. The early-time evolution of the photospheric velocity and temperature derived from the modeling agree with the behavior observed from other previously studied cases. The strong suppression of hydrogen Balmer lines in the spectra suggests interaction with a preexisting circumstellar environment could be occurring at early times. In the SN 2022wsp spectra, the absorption component of the Mg II P Cygni profile displays a double-trough feature on day +10 that disappears by day +20. The shape is well reproduced by the model without fine-tuning the parameters, suggesting that the secondary blueward dip is a metal transition that originates in the SN ejecta
Measuring Clients’ Perception of Functional Limitations Using the Perceived Functioning & Health Questionnaire
Background The Perceived Functioning & Health (PFH) questionnaire was developed to collect, in a standardized manner, which work activities are limited due to health conditions according to the perception of the client. In this study the questionnaire’s reliability and validity are investigated. Methods The PFH questionnaire is comprised of 147 questions, distributed over 33 scales, pertaining to the client’s psychosocial and physical work limitations. The PFH data of 800 respondents were analyzed: 254 healthy employees, 408 workers on sick leave and 138 recipients of a disability pension. Internal consistency (Cronbach’s α) for the scales was established. The test–retest reliability was examined for the data of 52 recipients of a disability pension who filled out the PFH twice within an interval of 1 month. Validation was established by taking the nature of the limitations as a criterion: mental limitations, physical limitations or a mix of both. To this end, the respondents were divided into groups distinguished on the basis of self-classification, as well as classification on the basis of disease codes given by insurance and occupational health physicians: a “healthy” group, subjects with only physical (“physical” group) or mental limitations (“mental” group) or mixed limitations (“mixed” group). The scale scores of these groups were compared and tested using analyses-of-variance and discriminant analyses. Results The scales were found to have sufficient to good internal consistency (mean Cronbach’s-α = 0.79) and test–retest reliability (mean correlation r = 0.76). Analyses-of-variance demonstrated significant differences between the scores of the mental, physical and healthy groups on most of the expected scales. These results were found both in groups defined by self-classification as well as in groups based on disease codes. Moreover, discriminant analyses revealed that the a priori classification of the respondents into three groups (mental, physical, healthy) for more than 75% of them corresponded with the classification on the basis of scale scores obtained from the questionnaire. Furthermore, limitations due to specific types of complaints (low back pain, fatigue, concentration problems) or diagnosed disorders (musculoskeletal disorders, reactive disorders, endogenous disorders) were clearly reflected in the scores of the related scales of the PFH. Conclusion The psychometric properties of the PFH with respect to reliability and validity were satisfactory. The PFH would appear to be an appropriate instrument for systematically measuring functional limitations in subjects on sick leave and in those receiving disability pensions, and could be used as a starting point in a disability claim procedure
Effect of Functional Capacity Evaluation information on the judgment of physicians about physical work ability in the context of disability claims
Purpose To test whether Functional Capacity Evaluation (FCE) information lead insurance physicians (IPs) to change their judgment about the physical work ability of claimants with musculoskeletal disorders (MSDs). Methods Twenty-seven IPs scored twice the physical work ability of two claimants for 12 specified activities, using a visual analogue scale. One claimant performed an FCE, the other served as a control. Outcome measure was the difference between experimental and control group in number of shifts in the physical work ability for the total of 12 specified activities. Results The IPs changed their judgment about the work ability 141 times when using FCE information compared to 102 times when not using this information (P-value = 0.001), both in the direction of more and less ability. Conclusions The IPs change their judgment of the physical work ability of claimants with MSDs in the context of disability claim procedures more often when FCE information is provide
Iliotibial band release as an adjunct to the surgical management of patellar stress fracture in the athlete: a case report and review of the literature
Stress fracture of the patella is rare. In this report, a case of patellar stress fracture occurring in an amateur athlete is presented, and an operative adjunct to the surgical management of this condition is proposed
Anti-tumor necrosis factor-Α antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust
Background/Aims Recent studies documented that sensitization and exposure to cockroach allergens significantly increase children's asthma morbidity as well as severity, especially among inner city children. TNF-Α has been postulated to be a critical mediator directly contributing to the bronchopulmonary inflammation and airway hyper-responsiveness in asthma. This study investigated whether an anti-TNF-Α antibody would inhibit pulmonary inflammation and methacholine (Mch) hyper-responsiveness in a mouse model of asthma induced by a house dust extract containing both endotoxin and cockroach allergens. Methods A house dust sample was extracted with phosphate-buffered saline and then used for immunization and two additional pulmonary challenges of BALB/c mice. Mice were treated with an intravenous injection of anti-TNF-Α antibody or control antibody 1 h before each pulmonary challenge. Results In a kinetic study, TNF-Α levels within the bronchoalveolar lavage (BAL) fluid increased quickly peaking at 2 h while BAL levels of IL-4, IL-5, and IL-13 peaked at later time-points. Mch hyper-responsiveness was measured 24 h after the last challenge, and mice were killed 24 h later. TNF inhibition resulted in an augmentation of these Th2 cytokines. However, the allergic pulmonary inflammation was significantly reduced by anti-TNF-Α antibody treatment as demonstrated by a substantial reduction in the number of BAL eosinophils, lymphocytes, macrophages, and neutrophils compared with rat IgG-treated mice. Mch hyper-responsiveness was also significantly reduced in anti-TNF-Α antibody-treated mice and the pulmonary histology was also significantly improved. Inhibition of TNF significantly reduced eotaxin levels within the lung, suggesting a potential mechanism for the beneficial effects. These data indicate that anti-TNF-Α antibody can reduce the inflammation and pathophysiology of asthma in a murine model of asthma induced by a house dust extract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73609/1/j.1365-2222.2005.02407.x.pd
- …