Advancing a Design for Trusted Community Bathymetry

The design for a Trusted Community Bathymetry (TCB) system, presented in Calder et al., 2020, demonstrates a data collection system capable of collecting precisely geo-referenced depth soundings from any navigational echosounder installed on a volunteer vessel. The TCB system is capable of autonomously determining any vertical installation offset with respect to the waterline, and provides sufficient guarantees of data quality to allow the soundings to be considered for hydrographic use. This thesis presents two contributions to advance the original TCB system design. First, it capitalizes on the widespread availability of low-cost sidescan modules in the recreational sonar market by describing a method to integrate one of these units with the existing TCB datalogger. This integration adds significant richness to a volunteer dataset by enabling a hydrographic office to benefit from imagery of targets and obstructions in the vicinity of TCB vessels. Additionally, a method for autonomous operation is presented in which the TCB datalogger may command the sidescan to automatically log imagery in the vicinity of targets of interest specified by the hydrographic office. Second, this work demonstrates it is possible to replace the survey-grade GNSS receiver antenna used in the original system design with a comparatively inexpensive unit. The replacement antenna does not provide equivalent real-time performance but can collect observations which can be post-processed to produce solutions with uncertainties on the same order as the survey-grade antenna. Since real-time performance is not important in a TCB application, this development represents a significant reduction in total system cost and increases the viability of widespread deployment without sacrificing data quality

Overcoming TGFβ-mediated immune evasion in cancer

This Review discusses the context-dependent functions of transforming growth factor-beta (TGF beta) with regard to the composition and behaviour of different cell populations in the tumour immune microenvironment, as well as emerging data that demonstrate that TGF beta inhibition can restore cancer immunity. Transforming growth factor-beta (TGF beta) signalling controls multiple cell fate decisions during development and tissue homeostasis; hence, dysregulation of this pathway can drive several diseases, including cancer. Here we discuss the influence that TGF beta exerts on the composition and behaviour of different cell populations present in the tumour immune microenvironment, and the context-dependent functions of this cytokine in suppressing or promoting cancer. During homeostasis, TGF beta controls inflammatory responses triggered by exposure to the outside milieu in barrier tissues. Lack of TGF beta exacerbates inflammation, leading to tissue damage and cellular transformation. In contrast, as tumours progress, they leverage TGF beta to drive an unrestrained wound-healing programme in cancer-associated fibroblasts, as well as to suppress the adaptive immune system and the innate immune system. In consonance with this key role in reprogramming the tumour microenvironment, emerging data demonstrate that TGF beta-inhibitory therapies can restore cancer immunity. Indeed, this approach can synergize with other immunotherapies - including immune checkpoint blockade - to unleash robust antitumour immune responses in preclinical cancer models. Despite initial challenges in clinical translation, these findings have sparked the development of multiple therapeutic strategies that inhibit the TGF beta pathway, many of which are currently in clinical evaluation

Variability and Constancy in Cellular Growth of Arabidopsis Sepals

Growth of tissues is highly reproducible; yet, growth of individual cells in a tissue is highly variable, and neighboring cells can grow at different rates. We analyzed the growth of epidermal cell lineages in the Arabidopsis (Arabidopsis thaliana) sepal to determine how the growth curves of individual cell lineages relate to one another in a developing tissue. To identify underlying growth trends, we developed a continuous displacement field to predict spatially averaged growth rates. We showed that this displacement field accurately describes the growth of sepal cell lineages and reveals underlying trends within the variability of in vivo cellular growth. We found that the tissue, individual cell lineages, and cell walls all exhibit growth rates that are initially low, accelerate to a maximum, and decrease again. Accordingly, these growth curves can be represented by sigmoid functions. We examined the relationships among the cell lineage growth curves and surprisingly found that all lineages reach the same maximum growth rate relative to their size. However, the cell lineages are not synchronized; each cell lineage reaches this same maximum relative growth rate but at different times. The heterogeneity in observed growth results from shifting the same underlying sigmoid curve in time and scaling by size. Thus, despite the variability in growth observed in our study and others, individual cell lineages in the developing sepal follow similarly shaped growth curves

Targeting the Microenvironment in Advanced Colorectal Cancer

Colorectal cancer (CRC) diagnosis often occurs at late stages when tumor cells have already disseminated. Current therapies are poorly effective for metastatic disease, the main cause of death in CRC. Despite mounting evidence implicating the tumor microenvironment in CRC progression and metastasis, clinical practice remains predominantly focused on targeting the epithelial compartment. Because CRCs remain largely refractory to current therapies, we must devise alternative strategies. Transforming growth factor (TGF)-β has emerged as a key architect of the microenvironment in poor-prognosis cancers. Disseminated tumor cells show a strong dependency on a TGF-β-activated stroma during the establishment and subsequent expansion of metastasis. We review and discuss the development of integrated approaches focused on targeting the ecosystem of poor-prognosis CRCs

\u201cNon \ue8 diverso da te\u201d. Una proposta di sensibilizzazione degli adolescenti al tema della salute mentale

L'articolo presenta un'esperienza di formazione e sensibilizzazione di studenti delle scuole superiori al tema della salute mentale e alcuni dei risultati della ricerca condotta in parallelo con i giovani per conoscere le loro opinioni sul tema prima e dopo la partecipazione a tale attivit\ue0

The SWISS-MODEL Repository: new features and functionalities

The SWISS-MODEL Repository is a database of annotated 3D protein structure models generated by the SWISS-MODEL homology-modelling pipeline. As of September 2005, the repository contained 675 000 models for 604 000 different protein sequences of the UniProt database. Regular updates ensure that the content of the repository reflects the current state of sequence and structure databases, integrating new or modified target sequences, and making use of new template structures. Each Repository entry consists of one or more 3D models accompanied by detailed information about the target protein and the model building process: functional annotation, a detailed template selection log, target-template alignment, summary of the model building and model quality assessment. The SWISS-MODEL Repository is freely accessible at

A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0

(1) Background: Virtual screening studies on the therapeutically relevant proteins of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) require a detailed characterization of their druggable binding sites, and, more generally, a convenient pocket mapping represents a key step for structure-based in silico studies; (2) Methods: Along with a careful literature search on SARS-CoV-2 protein targets, the study presents a novel strategy for pocket mapping based on the combination of pocket (as performed by the well-known FPocket tool) and docking searches (as performed by PLANTS or AutoDock/Vina engines); such an approach is implemented by the Pockets 2.0 plug-in for the VEGA ZZ suite of programs; (3) Results: The literature analysis allowed the identification of 16 promising binding cavities within the SARS-CoV-2 proteins and the here proposed approach was able to recognize them showing performances clearly better than those reached by the sole pocket detection; and (4) Conclusions: Even though the presented strategy should require more extended validations, this proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which are clearly amenable for virtual screening campaigns and drug repurposing studies. All results generated by the study and the Pockets 2.0 plug-in are available for download

A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion

Summary: Guided by a multi-level “deconstruction” of omental metastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human metastases and allowed malignant cell invasion into the artificial omental structure. Prompted by findings in patient biopsies, we used the model to investigate the role of platelets in malignant cell invasion and extracellular matrix, ECM, production. RNA (sequencing and quantitative polymerase-chain reaction), protein (proteomics and immunohistochemistry) and image analysis revealed that platelets stimulated malignant cell invasion and production of ECM molecules associated with poor prognosis. Moreover, we found that platelet activation of mesothelial cells was critical in stimulating malignant cell invasion. Whilst platelets likely activate both malignant cells and mesothelial cells, the tetra-culture model allowed us to dissect the role of both cell types and model the early stages of HGSOC metastases

Immunostaining Protocol: P-Smad2 (Xenograft and Mice)

Metastasis depends on a gene program expressed by the tumor microenvironment upon TGF-beta stimulation. CRC (Colorectal cancer) cell lines did not induce robust stromal TGF- beta responses when injected into nude mice as shown by lack of p- SMAD2 accumulation in tumor-associated stromal cells. To enforce high TGF-beta signaling in xenografts, we engineered CRC cell lines to secrete active TGF-beta. Subcutaneous tumors obtained from HT29-M6TGF-β, KM12L4aTGF-β cells and SW48TGF-β cells contained abundant p-SMAD2+ stromal cells