MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-!B in the nucleus of TNFa-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF’s partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein

Benzocaine and lidocaine induced methemoglobinemia after bronchoscopy: a case report

INTRODUCTION: Methemoglobinemia is a rare cause of hypoxemia, characterized by abnormal levels of oxidized hemoglobin that cannot bind to and transport oxygen. CASE PRESENTATION: A 62-year-old male underwent bronchoscopy where lidocaine oral solution and Hurricaine spray (20% benzocaine) were used. He developed central cyanosis and his oxygen saturation was 85% via pulse oximetry. An arterial blood gas revealed pH 7.45, P(CO2 )42, P(O2 )282, oxygen saturation 85%. Co-oximetry performed revealed a methemoglobin level of 17.5% (normal 0.6–2.5%). The patient was continued on 15 L/minute nonrebreathing face mask and subsequent oxygen saturation improved to 92% within two hours. With hemodynamic stability and improved SpO(2), treatment with methylene blue was withheld. CONCLUSION: Methemoglobinemia is a potentially lethal condition after exposure to routinely used drugs. Physicians should be aware of this complication for early diagnosis and treatment

Mechanisms and nutritional countermeasures to musculoskeletal disuse atrophy

Musculoskeletal disuse negatively impacts muscle mass and physiological functioning. Mechanistically, disuse-induced alterations in muscle mass are underpinned by alterations in myofibrillar protein turnover. However, the implications of disuse on mitochondrial functioning remains to be fully eluded. Accordingly, Chapter 2 explored whether a 7d period of reduced ambulation (<1,500 steps.d$^{-1}$) promoted alterations in skeletal muscle oxidative metabolism in young males. We report that 7d of reduced ambulation significantly reduced citrate synthase activity, without altering the abundance of proteins involved in mitochondrial functioning, mitochondrial dynamics, oxidative metabolism or skeletal muscle insulin signalling. Based on the importance of skeletal muscle anabolic sensitivity to prevent disuse induced atrophy, Chapter 3 assessed whether a high-dose leucine supplementation intervention could prevent alterations in fat free mass and strength during a 7d period of lower limb immobilization in young males. Here we report that there was a significant reduction in fat free mass (3.6 ± 0.5%) and strength (27.9 ± 4.4%) following 7d immobilization, with no effect of high-dose leucine supplementation compared with placebo. Mechanistically, disuse induced declines in fat free mass occurred in parallel to impaired MyoPS and mitochondrial protein synthesis (MitoPS) rates in the immobilised leg vs. control leg. Chapter 4 assessed the mechanistic ability of (-)-epicatechin (EPI) and its metabolite hippuric acid (HA) upon muscle morphology and metabolism within an in vitro model of atrophy. Under atrophy like conditions (24h dexamethasone (DEX)) C2C12 myotube diameter was significantly greater following co-incubation with either HA or EPI compared to the vehicle control (VC). Mechanistically, the co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates and partially attenuated proteolysis, preventing DEX-induced alterations in autophagic signalling. In conclusion, this thesis improved our understanding of the mechanisms underpinning disuse-induced muscle atrophy and the effectiveness of two nutritional countermeasures to prevent the negative physiological consequences of musculoskeletal disuse

A Systematic Review of Responsible Sourcing in the Architecture, Engineering, and Construction Sectors of the UK

In recent years, responsible sourcing and procurement (including green supply chain management) across the architecture, engineering, and construction (AEC) sectors have become notable contributors to sustainable construction strategies. This study aims to provide a systematic review of responsible sourcing literature across the AEC sectors of the UK to identify a suite of opportunities and obstacles to adopting ethical and environmentally supportive practices and to highlight avenues for further investigation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) review process was adopted to identify, screen, and select (n = 80) articles (from 2000–2020) for review. Analysis of these articles identified the most frequently reported opportunities: (i) stakeholder value (40%); (ii) improved supply chain performance (39%); and (iii) competitive advantage (30%). The most frequently reported obstacles relating to the uptake of responsible sourcing are the following: (i) cost (44%); (ii) industry constraints (28%); and (iii) lack of frameworks/information and lack of awareness (25%). Given the industry importance of these themes, it is proposed that there is a necessity to explore and unravel the perceptions of industry experts about these issues so as to clarify the progress and possibilities for more widely adopting responsible sourcing across the AEC sector and, moreover, for clarifying their contribution towards achieving national and international sustainability targets (e.g., UN Sustainable Development Goals)

South African urban youth responses to living in a world with COVID: Lessons from #Slam4urLife

Using poetry, visual art, songs, raps and sketches submitted to #Slam4urLife, a social media competition encouraging young people in South Africa to respond creatively to&nbsp;the COVID-19 pandemic, this article outlines young urban people’s responses to the COVID-19 pandemic in South Africa through four narratives: shock, loss, survival and activism. Resting on practices of engaged scholarship, it draws on knowledge bases and collaborations in and beyond the academy to contribute grounded research on arts-based social media competitions as an effective method for encouraging and amplifying the youth voice. It does this by creating digital public spaces in which young people can practise civic engagement in contexts where this cannot be done in physical public spaces. In doing so, the article contributes to the literature on community-based research and youth in African cities from the perspective of South Africa. It also argues the importance of art-based social media competitions in creating digital public spaces in which the&nbsp;youth voice can be encouraged, legitimised and amplified in so far as these kinds of digital spaces allow for a kind of civic engagement not always seen by young people in the physical public spaces of African cities

Sertoli – Leydigzelltumoren des Ovars: Analyse des Dicer1 – und Foxl2 – Mutationstatus

Purpose: Sertoli Leydig cell tumors (SLCT) are rare sex cord-stromal tumors of the ovary. Dicer1 mutations have been shown to be present in a majority of SLCT, while only few reported cases have harbored Foxl2 mutations. It was our aim to classify SLCTs according to their molecular profile and clinicopathological features. Methods: Formalin-fixed, paraffin-embedded tissue blocks from a cohort of 45 SLCT diagnosed between 1995 and 2016 were available after specialized gynecopathological review. Dicer1 mutation status was determined by Sanger Sequencing while Foxl2 402G>C mutation status was determined by TaqMan allelic discrimination assay. Clinical data sets were updated allowing for correlation with mutation status. Results: Dicer1 mutation analyses could be performed successfully in 44/45 SLCT, and 18/44 (41%) of cases were positive for at least 1 hotspot mutation. Dicer1 mutation-positive cases had a median age of 24,5 years (range 15-62 years). A majority (68,8%) of Dicer1 mutation-positive cases showed hyperandrogenic symptoms, and in 18,8% of patients, abnormal uterine bleeding was noted at presentation. Foxl2 mutation analyses was successfully done in all 45 cases, and 10/45 SLCT (22,2%) were 402G>C mutation positive. In this subgroup, the median age was 78,5 years (range 54-90 years). 4/5 (80%) of patients with Foxl2 mutation-positive SLCT had abnormal uterine bleeding at presentation. Conclusions: This study suggests that there are different molecular subtypes of SLCT. Dicer1 mutation-positive tumors occur in younger patients presenting with hyperandrogenic symptoms, whereas Foxl2 mutation-positive SLCT occur more frequently in postmenopausal women presenting with abnormal uterine bleeding

A Comparison of Radio and X-Ray Morphologies of Four Clusters of Galaxies Containing Radio Halos

Clusters of galaxies may contain cluster-wide, centrally located, diffuse radio sources, called halos. They have been found to show morphologies similar to those of the X-ray emission. To quantify this qualitative statement we performed a point-to-point comparison of the radio and the X-ray emission for four clusters of galaxies containing radio halos: Coma, Abell 2255, Abell 2319, Abell 2744. Our study leads to a linear relation between the radio and the X-ray surface brightness in two clusters, namely Abell 2255 and Abell 2744. In Coma and A2319 the radio and the X-ray brightnesses seem to be related with a sub-linear power law. Implications of these findings within simple radio halo formation models are briefly discussed.Comment: 9 pages, 13 .ps figures, accepted by A&

Inelegibilidade: conceito, efeitos e meios de arguição no Direito Eleitoral Brasileiro

A presente investigação tem por objeto de estudo a inelegibilidade, no âmbito das eleições políticas, tendo em consideração os seus possíveis significados e relação com outras expressões; os efeitos de sua constatação judicial; e os meios disponíveis para sua arguição, na ordem jurídica brasileira. Buscou-se, por meio de revisão bibliográfica, a explicitação de pontos introdutórios, mas pouco referenciados pela doutrina brasileira, por entender-se de reconhecida importância para uma correta compreensão do instituto da inelegibilidade, que está compreendida na fase das candidaturas. A perspectiva da análise é dogmática, uma vez que tem por fim último a aplicação das normas jurídicas referentes à inelegibilidade, oferecendo-se, com ela, um novo texto acerca do discurso legislativo. Em resposta aos questionamentos realizados, concluiu-se que a inelegibilidade possui várias acepções jurídicas (hipóteses que obstam a capacidade eleitora passiva; incapacidade; e sanção jurídica); que sua configuração produz o indeferimento/invalidade do registro da candidatura ou do diploma do eleito; e que sua verificação se dá pelo Poder Judiciário, de ofício ou mediante a sua arguição por meio das ações pertinentes