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• Elucidation of minimal glycan epitopes is key for vaccine design. • Application of structural glycobiology to conjugate vaccines enables identification of relevant glycan epitopes. • We solved by X-ray crystallography the highly complex epitope from GBSIII capsular polysaccharide complexed with a Fab. • Based on this information a synthetic glycan was designed and protein conjugate to induce a strong immune response. • This approach can be extended to other GBS polysaccharides as well as glycans from other pathogens. Microbial surface polysaccharides are important virulence factors and targets for vaccine development. Glycoconjugate vaccines, obtained by covalently linking carbohydrates and proteins, are well established tools for prevention of bacterial infections. Elucidation of the minimal portion involved in the interactions with functional antibodies is of utmost importance for the understanding of their mechanism of induction of protective immune responses and the design of synthetic glycan based vaccines. Typically, this is achieved by combination of different techniques, which include ELISA, glycoarray, Surface Plasmon Resonance in conjunction with approaches for mapping at atomic level the position involved in binding, such as Saturation Transfer NMR and X-ray crystallography. This review provides an overview of the structural studies performed to map glycan epitopes (glycotopes), with focus on the highly complex structure of Group B Streptococcus type III (GBSIII) capsular polysaccharide. Furthermore, it describes the rational process followed to translate the obtained information into the design of a protective glycoconjugate vaccine based on a well-defined synthetic glycan epitope. [ABSTRACT FROM AUTHOR]

Abstract The NW Borneo margin is characterized by a complex deepwater fold-and-thrust belt. Despite previous studies, the definition of a univocal detachment level for folding and thrusting is still lacking. The area-depth-strain (ADS) method can be used to determine the location for a detachment in areas lacking data, and to balance geological cross sections. This study applies the ADS method to the central part of the NW Borneo fold-and-thrust belt to predict a structurally conclusive detachment level in an area lacking a seismic detachment reflection. Seismic interpretations were completed after the ADS-determination of the basal detachment, providing input for a 2D sequential restoration that delivered values on shortening distribution and shortening rate. The kinematic and mechanic analyses presented, document that the central part of the NW Borneo fold-and-thrust belt is affected by both, near- and far-field stresses, and that the far-field crustal shortening component becomes more important northward. This work demonstrates that the ADS method can be effectively applied in fold-thrust belt settings with limited information on the detachment, supports in a quantitative way the tectonic and stratigraphic interpretation of seismic-reflection data and provides a robust structural base for the restoration of balanced cross-sections, including the reconstruction of syn-kinematically eroded stratigraphy. Highlights • The ADS method was applied to estimate a reliable depth of the basal detachment. • The landward-dipping detachment dips about 1.9° between ∼5 km and 8.7 km depth. • Detachment depth generally decreases southward. • The wedge taper angle is representative of a mixed near- and far-field stress DWFTB. • Most of the shortening occurred mainly in the last ∼3.6 Ma at a rate of ∼3 mm/yr. [ABSTRACT FROM AUTHOR]

The Mt. Vettore area is located in the Central Apennines (Italy), a region characterized by intense seismic activity that has recorded multiple moderate-to-high magnitude seismic sequences. The seismic activity is due to the presence of normal fault systems, among which is the Mt. Vettore Fault System (VFS), which was last activated during the 2016-17 Central Italy seismic sequence.. Moreover, the region has experienced three major tectonic phases over geological history, thus it is important to unravel their contribution to the current fracture network. Based on the integration of field observation with Unmanned Aerial Vehicle - Digital Photogrammetry data, we aim to analyze the fracture network on eight different outcrops located at different structural positions with respect to VFZ. Results show that the Late Miocene−Early Pliocene compressional phase deeply affected the present-day fracture pattern, which is especially related to the evolution of the Mt. Sibillini regional thrust and its related anticline. The present-day Quaternary extensional phase, and the associated normal faults, mostly reactivate some of the pre-existing fracture sets. • Definition of the main fracture sets in the Jurassic Calcare Massiccio formation in the Mt. Vettore Area. • Definition of the fracture intensity variation in different structural position along the study area. • Definition of the cross cutting relation between the main fracture sets. [ABSTRACT FROM AUTHOR]

Carbohydrates are abundantly expressed on the surface of both eukaryotic and prokaryotic cells, often as post translational modifications of proteins. Glycoproteins are recognized by the immune system and can trigger both innate and humoral responses. This feature has been harnessed to generate vaccines against polysaccharide-encapsulated bacteria such as Streptococcus pneumoniae , Hemophilus influenzae type b and Neisseria meningitidis. In cancer, glycosylation plays a pivotal role in malignancy development and progression. Since glycans are specifically expressed on the surface of tumor cells, they have been targeted for the discovery of anticancer preventive and therapeutic treatments, such as vaccines and monoclonal antibodies. Despite the various efforts made over the last years, resulting in a series of clinical studies, attempts of vaccination with carbohydrate-based candidates have proven unsuccessful, primarily due to the immune tolerance often associated with these glycans. New strategies are thus deployed to enhance carbohydrate-based cancer vaccines. Moreover, lessons learned from glycan immunobiology paved the way to the development of new monoclonal antibodies specifically designed to recognize cancer-bound carbohydrates and induce tumor cell killing. Herein we provide an overview of the immunological principles behind the immune response towards glycans and glycoconjugates and the approaches exploited at both preclinical and clinical level to target cancer-associated glycans for the development of vaccines and therapeutic monoclonal antibodies. We also discuss gaps and opportunities to successfully advance glycan-directed cancer therapies, which could provide patients with innovative and effective treatments. [ABSTRACT FROM AUTHOR]