Analysis of the lipid binding properties of mutant murine Bid proteins

Bid is a BH3-only member of the Bcl-2 family that regulates cell death at the level of mitochondrial membranes. It is generally assumed that the full length Bid protein becomes activated after a proteolytic cleavage catalized by apical caspases, like caspase 8. The cleaved protein then re-locates to mitochondria and promotes membrane permeabilization, presumably by interaction with mitochondrial lipids and other Bcl-2 proteins that facilitate the release of apoptogenic proteins like cytochrome c. The un-cleaved Bid also has proapoptotic potential when ectopically expressed in cells or in vitro. It has been demonstrated that full length Bid can insert specific lysolipids into the membrane surface and this lipid transfer activity participates to the release of apoptogenic factors from mitochondria. The binding properties of Bid are still unknown. In this work we will present new full length Bid mutants that possess altered lipid binding properties and proapoptotic activities in vitro. We have analysed the binding properties of Bid mutants to LPC species and MCL (or LPG) in order to investigate the protein dual specificity for the diverse lysolipids

The role of life cycle thinking-based methodologies in the development of waste management plans

The aim of this article is to examine how Life Cycle Thinking (LCT) contributes to the development of Waste Management Plans (WMPs). The case of Italy has been deeply investigated. The article first analyses whether and how the LCT methodologies were applied to the 21 regional WMPs; then, it draws indications for using LCT in the preparation of a WMP. Moreover, it outlines why the Life Cycle Assessment (LCA) methodology could be used as a powerful tool for regional planning in the waste field, analysing the indications for preparing a WMP that already exist at the European level and in the Italian National WM Programme. Results reveal that only four of the 21 regional WMPs include comprehensive and site-specific LCA studies. Building on these case study results, insights into the opportunities and benefits associated with incorporating LCT methodologies into WMP development and implementation are provided. This study underscores the critical importance of LCT and LCA in promoting sustainable waste management practices, ensuring compliance with European directives, and offering a foundation for more informed regional planning strategies

APPLICAZIONI DELLA METODOLOGIA LCA NEL CAMPO DELLA GESTIONE E DEL TRATTAMENTO DEI RIFIUTI

L\u2019articolo nasce da un\u2019iniziativa del gruppo di lavoro \u201cGestione e trattamento dei rifiuti\u201d dell\u2019Associazione Rete Italiana LCA (Life Cycle Assessment). L\u2019obiettivo principale del gruppo di lavoro \ue8 quello di ampliare le conoscenze relative alla specificit\ue0 della metodologia LCA applicata ai processi di gestione e di trattamento dei rifiuti. L\u2019articolo riporta otto casi studio condotti da alcuni dei partecipanti al gruppo di lavoro, con il duplice obiettivo di mostrare il vasto campo di applicazione della metodologia LCA pur mantenendosi all\u2019interno del settore rifiuti e le specificit\ue0 dell\u2019applicazione di tale metodologia ai processi di gestione e trattamento dei rifiuti. Gli otto casi studio sono stati raggruppati per macro-finalit\ue0 dell\u2019applicazione, ossia: LCA applicata per valutare i benefici ottenibili dal recupero di varie tipologie di rifiuti, LCA a supporto della pianificazione regionale e/o nazionale e LCA a supporto dell\u2019economia circolare

D21.3 Analysis of initial results at EuWIN@CTTC

Deliverable D21.3 del projecte europeu NEWCOM#The nature of this Deliverable of WP2.1 (“Radio interfaces for next-generation wireless systems”) is mainly descriptive and its purpose is to provide a report on the status of the different Joint Research Activities (JRAs) currently ongoing, some of them being performed on the facilities that are available at EuWInPeer ReviewedPreprin

Spoligotyping and Mycobacterium tuberculosis

Speed of spoligotyping could be a benefit in the clinical setting

Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population

BACKGROUND: Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. METHODOLOGY/PRINCIPAL FINDINGS: This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. CONCLUSION: The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG

The Role of Schools in Early Adolescents’ Mental Health: Findings from the MYRIAD Study

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordData Sharing: The corresponding study protocol can be found at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1917-4. R code is available from the Open Science Framework (https://osf.io/s63fm/?view_only=5ae58f6c053c4a16b5ddfccd0e6e1ece). The baseline data and codebook from the MYRIAD trial is available from Prof. Kuyken ([email protected]) upon request (release of data is subject to an approved proposal and a signed data access agreement).Objective: Recent studies suggest deteriorating youth mental health. The current UK policy emphasises the role of schools for mental health promotion and prevention, but little data exist on what aspects of schools explain pupils’ mental health. We explored school-level influences on the mental health of young people in a large school-based sample from the UK. Methods: We analysed baseline data from a large cluster randomized controlled trial (ISRCTN 86619085) collected between 2016‒2018 from mainstream UK secondary schools selected to be representative in relation to their quality rating, size, deprivation, mixed or single-sex pupil population and country. Participants were pupils in their first or second year of secondary school. We assessed whether school-level factors were associated with pupil mental health. Results: 26,885 pupils (response rate=90%), aged 11‒14 years, 55% female, attending 85 UK schools, were included. Schools accounted for 2.4% (95% CI=2.0‒2.8; p<0.0001) of the variation in psychopathology, 1.6% (95% CI=1.2‒2.1; p<0.0001) of depression and 1.4% (95% CI=1.0‒1.7; p<0.0001) of well-being. Schools in urban locations, with a higher percentage of free school meals and of White British, were associated with poorer pupil mental health. A more positive school climate was associated with better mental health. Conclusion: School-level variables, primarily related to contextual factors, characteristics of their pupil population, and school climate explain a small but significant amount of variability in young people’s mental health. This might be used to identify schools that are in need of more resources to support young people’s mental health.Wellcome TrustNational Institute for Health Research (NIHR)Medical Research Council (MRC