The baculovirus anti-apoptotic protein Op-IAP does not inhibit Drosophila caspases or apoptosis in Drosophila S2 cells and instead sensitizes S2 cells to virus-induced apoptosis

AbstractThe Op-IAP protein from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) is highly effective at inhibiting apoptosis triggered by a variety of different stimuli in lepidopteran cells as well as in several different mammalian cell types, suggesting that it functions at a highly conserved step in the apoptotic pathway. However, the mechanism by which Op-IAP inhibits apoptosis is unclear. Since some IAP proteins can bind and inhibit caspases, we tested whether Op-IAP could inhibit the activity of caspases from Drosophila melanogaster. We found that recombinant Op-IAP protein was not able to bind or directly inhibit the activity of the Drosophila caspases DRONC, DrICE, or DCP-1 in vitro. In addition, expression of Op-IAP was unable to inhibit apoptosis triggered by either actinomycin D or UV light in D. melanogaster S2 cells. Surprisingly, Op-IAP expression in S2 cells enhanced apoptosis caused by baculovirus infection, but did not cause increased sensitivity to either actinomycin D or UV damage-induced apoptosis. The observation that Op-IAP cannot inhibit these insect caspases suggests that it functions by a mechanism that does not involve direct caspase inhibition

A Framework for Understanding the Role of Psychological Processes in Disease Development, Maintenance, and Treatment: The 3P-Disease Model

Health psychology is multidisciplinary, with researchers, practitioners, and policy makers finding themselves needing at least some level of competency in a variety of areas from psychology to physiology, public health, and others. Given this multidisciplinary ontology, prior attempts have been made to establish a framework for understanding the role of biological, psychological, and socio-environmental constructs in disease development, maintenance, and treatment. Other models, however, do not explain how factors may interact and develop over time. The aim here was to apply and adapt the 3P model, originally developed and used in the treatment of insomnia, to couch the biopsychosocial model in a way that explains how diseases develop, are maintained, and can be treated. This paper outlines the role of predisposing, precipitating, and perpetuating factors in disease states and conditions (the 3Ps) and provides examples of how this model may be adapted and applied to a number of health-related diseases or disorders including chronic pain, gastrointestinal disorders, oral disease, and heart disease. The 3P framework can aid in facilitating a multidisciplinary, theoretical approach and way of conceptualizing the study and treatment of diseases in the future

Periodontal Status and Quality of Life: Impact of Fear of Pain and Dental Fear

Background. Oral health-related quality of life (OHRQoL) is impacted by periodontal disease and orofacial pain. There is a limited research examining the impact of avoidance of care or physiological arousal related to the fear of pain response on periodontal-related OHRQoL. Methods. Data are from the Center for Oral Health Research in Appalachia family-based study focusing on 1,339 adults. Measures included a modified Periodontal Screening and Recording Index across sextants of dentition, dental fear survey, Fear of Pain Questionnaire-9, and Oral Health Impact Profile-14. Structural equation modeling was used to estimate the effects of periodontal disease screening indicators on OHRQoL including the mediating role of dental fear while accounting for fear of pain. Results. A significant total effect was found for the mandibular anterior sextant, components of dental anxiety/fear, and indicators of OHRQoL (pain and discomfort, , ; psychosocial impact, , ). The maxillary anterior region was significantly associated with pain discomfort (, ) and functionality (, ). Conclusions. Findings provide a granular perspective of periodontal disease indicators and OHRQoL. Dental avoidance/anticipatory fear and physiological arousal mediate OHRQoL in individuals who have indicators of periodontal disease in sextants that may be visible and susceptible to higher pain and psychosocial impact

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

Background. Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods. A genome-wide association study (GWAS; ) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain

Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance to tumorigenesis

To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling

DustPedia: Multiwavelength photometry and imagery of 875 nearby galaxies in 42 ultraviolet-microwave bands

Aims. The DustPedia project is capitalising on the legacy of the Herschel Space Observatory, using cutting-edge modelling techniques to study dust in the 875 DustPedia galaxies – representing the vast majority of extended galaxies within 3000 km s-1 that were observed by Herschel. This work requires a database of multiwavelength imagery and photometry that greatly exceeds the scope (in terms of wavelength coverage and number of galaxies) of any previous local-Universe survey. Methods. We constructed a database containing our own custom Herschel reductions, along with standardised archival observations from GALEX, SDSS, DSS, 2MASS, WISE, Spitzer, and Planck. Using these data, we performed consistent aperture-matched photometry, which we combined with external supplementary photometry from IRAS and Planck. Results. We present our multiwavelength imagery and photometry across 42 UV-microwave bands for the 875 DustPedia galaxies. Our aperture-matched photometry, combined with the external supplementary photometry, represents a total of 21 857 photometric measurements. A typical DustPedia galaxy has multiwavelength photometry spanning 25 bands. We also present the Comprehensive & Adaptable Aperture Photometry Routine (CAAPR), the pipeline we developed to carry out our aperture-matched photometry. CAAPR is designed to produce consistent photometry for the enormous range of galaxy and observation types in our data. In particular, CAAPR is able to determine robust cross-compatible uncertainties, thanks to a novel method for reliably extrapolating the aperture noise for observations that cover a very limited amount of background. Our rich database of imagery and photometry is being made available to the community

Two distinct signalling cascades target the NF-κB regulatory factor c-IAP1 for degradation

c-IAP1 (cellular inhibitor of apoptosis 1) has recently emerged as a negative regulator of the non-canonical NF-κB (nuclear factor κB) signalling cascade. Whereas synthetic IAP inhibitors have been shown to trigger the autoubiquitination and degradation of c-IAP1, less is known about the physiological mechanisms by which c-IAP1 stability is regulated. In the present paper, we describe two distinct cellular processes that lead to the targeted loss of c-IAP1. Recruitment of a TRAF2 (tumour necrosis factor receptor-associated factor 2)–c-IAP1 complex to the cytoplasmic domain of the Hodgkin's/anaplastic large-cell lymphoma-associated receptor, CD30, leads to the targeting and degradation of the TRAF2–c-IAP1 heterodimer through a mechanism requiring the RING (really interesting new gene) domain of TRAF2, but not c-IAP1. In contrast, the induced autoubiquitination of c-IAP1 by IAP antagonists causes the selective loss of c-IAP1, but not TRAF2, thereby releasing TRAF2. Thus c-IAP1 can be targeted for degradation by two distinct processes, revealing the critical importance of this molecule as a regulator of numerous intracellular signalling cascades

LOFAR/H-ATLAS: The low-frequency radio luminosity - star-formation rate relation

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society.Radio emission is a key indicator of star-formation activity in galaxies, but the radio luminosity-star formation relation has to date been studied almost exclusively at frequencies of 1.4 GHz or above. At lower radio frequencies the effects of thermal radio emission are greatly reduced, and so we would expect the radio emission observed to be completely dominated by synchrotron radiation from supernova-generated cosmic rays. As part of the LOFAR Surveys Key Science project, the Herschel-ATLAS NGP field has been surveyed with LOFAR at an effective frequency of 150 MHz. We select a sample from the MPA-JHU catalogue of SDSS galaxies in this area: the combination of Herschel, optical and mid-infrared data enable us to derive star-formation rates (SFRs) for our sources using spectral energy distribution fitting, allowing a detailed study of the low-frequency radio luminosity--star-formation relation in the nearby Universe. For those objects selected as star-forming galaxies (SFGs) using optical emission line diagnostics, we find a tight relationship between the 150 MHz radio luminosity ($L_{150}$) and SFR. Interestingly, we find that a single power-law relationship between $L_{150}$ and SFR is not a good description of all SFGs: a broken power law model provides a better fit. This may indicate an additional mechanism for the generation of radio-emitting cosmic rays. Also, at given SFR, the radio luminosity depends on the stellar mass of the galaxy. Objects which were not classified as SFGs have higher 150-MHz radio luminosity than would be expected given their SFR, implying an important role for low-level active galactic nucleus activity.Peer reviewedFinal Published versio

Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction

<p>Abstract</p> <p>Background</p> <p>Generalized hypoxic pulmonary vasoconstriction (HPV) occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebulization of nitrite and different formulations of acidified sodium nitrite on acute HPV.</p> <p>Methods</p> <p><it>Ex vivo </it>isolated rabbit lungs perfused with erythrocytes in Krebs-Henseleit buffer (adjusted to 10% hematocrit) and <it>in vivo </it>anesthetized catheterized rabbits were challenged with periods of hypoxic ventilation alternating with periods of normoxic ventilation. After baseline hypoxic challenges, vehicle, sodium nitrite or acidified sodium nitrite was delivered via nebulization. In the <it>ex vivo </it>model, pulmonary arterial pressure and nitric oxide concentrations in exhaled gas were monitored. Nitrite and nitrite/nitrate were measured in samples of perfusion buffer. Pulmonary arterial pressure, systemic arterial pressure, cardiac output and blood gases were monitored in the <it>in vivo </it>model.</p> <p>Results</p> <p>In the <it>ex vivo </it>model, nitrite nebulization attenuated HPV and increased nitric oxide concentrations in exhaled gas and nitrite concentrations in the perfusate. The acidified forms of sodium nitrite induced higher levels of nitric oxide in exhaled gas and had longer vasodilating effects compared to nitrite alone. All nitrite formulations increased concentrations of circulating nitrite to the same degree. In the <it>in vivo </it>model, inhaled nitrite inhibited HPV, while pulmonary arterial pressure, cardiac output and blood gases were not affected. All nitrite formulations had similar potency to inhibit HPV. The tested concentration of appeared tolerable.</p> <p>Conclusion</p> <p>Nitrite alone and in acidified forms effectively and similarly attenuates HPV. However, acidified nitrite formulations induce a more pronounced increase in nitric oxide exhalation.</p