Atomic-Scale Mapping and Quantification of Local Ruddlesden-Popper Phase Variations

The Ruddlesden-Popper (An+1BnO3n+1) compounds are highly tunable materials whose functional properties can be dramatically impacted by their structural phase n. The negligible differences in formation energies for different n can produce local structural variations arising from small stoichiometric deviations. Here, we present a Python analysis platform to detect, measure, and quantify the presence of different n-phases based on atomic-resolution scanning transmission electron microscopy (STEM) images. We employ image phase analysis to identify horizontal Ruddlesden-Popper faults within the lattice images and quantify the local structure. Our semiautomated technique considers effects of finite projection thickness, limited fields of view, and lateral sampling rates. This method retains real-space distribution of layer variations allowing for spatial mapping of local n-phases to enable quantification of intergrowth occurrence and qualitative description of their distribution suitable for a wide range of layered materials

How Allosteric Control of Staphylococcus aureus Penicillin-Binding Protein 2a Enables Methicillin-Resistance and Physiological Function

The expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the β-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The highmolecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In bacteria susceptible to β-lactam antibiotics, the transpeptidase activity of their penicillin binding proteins (PBPs) is lost as a result of irreversible acylation of an active site serine by the β-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to β-lactam acylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The inability to contain MRSA infection with β-lactam antibiotics is a continuing public health concern. We report herein the identification of an allosteric binding domain - a remarkable 60 Å distant from the DD-transpeptidase active site - discovered by crystallographic analysis of a soluble construct of PBP2a. When this allosteric site is occupied, a multiresidue conformational change culminates in the opening of the active site to permit substrate entry. This same crystallographic analysis also reveals the identity of three allosteric ligands: muramic acid (a saccharide component of the peptidoglycan), the cell wall peptidoglycan, and ceftaroline, a recently approved anti-MRSA β-lactam antibiotic. The ability of an anti-MRSA β-lactam antibiotic to stimulate allosteric opening of the active site, thus predisposing PBP2a to inactivation by a second β-lactam molecule, opens an unprecedented realm for β-lactam antibiotic structure-based design.Fil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Rojas Altuve, Alzoray. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; EspañaFil: Llarrull, Leticia Irene. University of Notre Dame; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Carrasco López, Cesar. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; EspañaFil: Kumarasiri, Malika. University of Notre Dame; Estados UnidosFil: Lastochkin, Elena. University of Notre Dame; Estados UnidosFil: Fishovitz, Jennifer. University of Notre Dame; Estados UnidosFil: Dawley, Matthew. University of Notre Dame; Estados UnidosFil: Hesek, Dusan. University of Notre Dame; Estados UnidosFil: Lee, Mijoon. University of Notre Dame; Estados UnidosFil: Johnson, Jarrod W.. University of Notre Dame; Estados UnidosFil: Fisher, Jed F.. University of Notre Dame; Estados UnidosFil: Chang, Mayland. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados UnidosFil: Hermoso, Juan A.. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; Españ

Disruption of Allosteric Response as an Unprecedented Mechanism of Resistance to Antibiotics

Ceftaroline, a recently approved β-lactam antibiotic for treatment of infections by methicillinresistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that impairs cell-wall biosynthesis and leads to bacterial death. The triggering of the allosteric effect takes place by binding of the first antibiotic molecule 60 Å away from the active site of PBP2a within the core of the allosteric site. We document, by kinetic studies and by determination of three X-ray structures of the mutant variants of PBP2a that result in resistance to ceftaroline, that the effect of these clinical mutants is the disruption of the allosteric trigger in this important protein in MRSA. This is an unprecedented mechanism for antibiotic resistance.Fil: Fishovitz, Jennifer. University of Notre Dame. Department of Chemistry and Biochemistry; Estados UnidosFil: Rojas Altuve, Alzoray. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; EspañaFil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Dawley, Matthew. University of Notre Dame. Department of Chemistry and Biochemistry; Estados UnidosFil: Carrasco López, Cesar. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; EspañaFil: Chang, Mayland. University of Notre Dame. Department of Chemistry and Biochemistry; Estados UnidosFil: Hermoso, Juan Antonio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; EspañaFil: Mobashery, Shahriar. University of Notre Dame. Department of Chemistry and Biochemistry; Estados Unido

A Pesquisa sobre Identidade e Cidadania nos EUA: da Nova História Social à Nova História Cultural

O presente artigo analisa as novas tendências da historiografia norte-americana a respeito da cidadania e da identidade, evidenciando os deslocamentos ocorridos tanto na escolha dos objetos de pesquisa quanto na abordagem. A passagem da história social para a história cultural implicou em rupturas significativas e abriu novas direções de pesquisa, perceptível na produção mais recente.<br>The present article deals with the new tendencies of north american historiography about citizenship and identity, emphasizing the birth of different choices on research subjects and approaches. The move from social history to cultural history meant important ruptures and opened new directions of research which are visible in the most recent literature