Transmembrane Protein Docking with JabberDock

Transmembrane proteins act as an intermediary for a broad range of biological process. Making up 20% to 30% of the proteome, their ubiquitous nature has resulted in them comprising 50% of all targets in drug design. Despite their importance, they make up only 4% of all structures in the PDB database, primarily owing to difficulties associated with isolating and characterizing them. Membrane protein docking algorithms could help to fill this knowledge gap, yet only few exist. Moreover, these existing methods achieve success rates lower than the current best soluble proteins docking software. We present and test a pipeline using our software, JabberDock, to dock membrane proteins. JabberDock docks shapes representative of membrane protein structure and dynamics in their biphasic environment. We verify JabberDock’s ability to yield accurate predictions by applying it to a benchmark of 20 transmembrane dimers, returning a success rate of 75.0%. This makes our software very competitive among available membrane protein–protein docking tools

Case Study: The analysis of an integrated project management.

Textile is still considered as special waste, and in the Metropolitan Area of Turin 4.960 tons (Città Metropolitana di Torino, 2020) of it are collected every year. This aspect, among others, is one of the challenges that this territory is confronting. The research paper has the aim to show the results that emerged from the state of the art of a specific area in Italy. These data are then confronted with information about a local company, Dual Sanitaly, that produces and distributes textile medical devices throughout Italy. The analysis is the starting point of a shift from a linear to a systemic process. The application of the holistic approach helped to focus both on the aspects that define both physically and socially the Metropolitan Area of Turin and on the flows of energy, matter and information of the company. The collection of data follows a path that goes from macro to micro and from a generic point of view to specific topics and aspects. The ultimate goal is to have a solid base from which to identify challenges and opportunities, both in the territory and in the company, to understand which elements are fundamental to create a systemic pattern of people, projects and stories

Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin

Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function

Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression

MmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalactan. MmpL3 represents an emerging target for tuberculosis therapy. In this paper, we describe the construction and characterization of an mmpL3 knockdown strain of M. tuberculosis. Downregulation of mmpL3 led to a stop in bacterial division and rapid cell death, preceded by the accumulation of TDM precursors. MmpL3 was also shown to be essential for growth in monocyte-derived human macrophages. Using RNA-seq we also found that MmpL3 depletion caused up-regulation of 47 genes and down-regulation of 23 genes (at least 3-fold change and false discovery rate <= 1%). Several genes related to osmoprotection and metal homeostasis were induced, while several genes related to energy production and mycolic acids biosynthesis were repressed suggesting that inability to synthesize a correct outer membrane leads to changes in cellular permeability and a metabolic downshift

A Meta-Analysis for an Interactive, Intersectional and Inclusive Exhibition Based on the SDGs

The main goal of the project is to create an interactive exhibition, innovative and technological in its approach, that aims to create awareness and promote the knowledge of the Sustainable Development Goals of the Agenda ONU 2030 – in particular, on the value of social and environmental sustainability. 178 Countries adopted a common agenda to preserve our planet for the first time in 1992, during the Rio de Janeiro Summit. From that moment, the concept of sustainability has changed forever and has been changing ever since. In this paper, after understanding the state of the art in the field of the interactive exhibition, it is going to be explained how the methodology is applied in order to evolve from a desk and field analysis to a concept definition. These key points will then help define the concept in the shape of an operative strategy with methodological guidelines and a structured solution. From this stage, a few considerations on the future of this proposal can be drawn

Databook design per fare innovazione. Uno strumento di ricerca e analisi per attivare progettualità sostenibili

I recenti eventi globali hanno dimostrato come i dati, parametri quanti-qualitativi, ben definiti e condivisi, siano in grado di fornire una sintesi esaustiva di fenomeni complessi. All’interno della Systemic Innovation Design Methodology, la fase iniziale di rilievo olistico individua nei dati e nella loro mappatura una risorsa esaustiva per la descrizione di un contesto: alla base di questo processo, la progettazione stessa del rilievo offre al progettista metodi di analisi la cui unione e sistematizzazione permettono la restituzione della complessità attraverso la loro visualizzazione. Il risultato di tale analisi è un Databook, un documento analogico-digitale dove tutte le informazioni raccolte vengono filtrate, organizzate e relazionate così da poter essere facilmente interpretabili. Uno strumento che nasce per essere il punto di partenza della fase di concept al servizio del designer e/o di enti terzi. Attraverso questi principi, il contributo esplora il Databook come strumento in grado di generare conoscenza tramite una visualizzazione chiara ed efficace, individuando, tramite un sistema di analisi e valutazione, i punti di forza, le criticità e le aree di implementazione

Multicenter comparative multimodality surveillance of women at genetic-familial risk for breast cancer (HIBCRIT study): interim results.

PURPOSE: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material-enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic findings as standard. MATERIALS AND METHODS: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first- or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age). RESULTS: Two hundred seventy-eight women (mean age, 46 years +/- 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were <or=10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BRCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 95%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%). CONCLUSION: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers. (c) RSNA, 2007