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The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

In this article, the authors tell the story of one family's journey toward healing using the Child First home visiting and Circle of Security Parenting interventions. Parents with complex trauma histories frequently float through services for years looking for guidance to help them address their struggles. Often, these services do not offer interventions with a trauma frame or address the significance of the parental role. The authors highlight how programs can enhance their efforts with families by mindfully integrating models of treatment and parent education in ways that are sensitive to parental trauma. They also discuss important home visiting model components that elicit success.

Debates on positionality and partisanship in the research process are long-standing, complex and often highly contentious. Engaging with, and contributing to, both these key debates, this paper introduces the concept of victim-as-researcher. This draws from the author's experiences of undertaking research in Trinidad and Tobago with a group of offenders who had committed similar offences to that which the researcher was herself a victim. There is a paucity of literature which speaks to the experiences of victims of serious, violent crime who subsequently engage in qualitative research with offenders who have been convicted of offences similar to the ones experienced by the researcher and which, therefore, can elicit trauma whilst in the field and through analysis. This paper aims to extend the methodological literature on positionality and victimology by foregrounding the victim-as-researcher as an important category in reflexive sociological and criminological research. [ABSTRACT FROM AUTHOR]

It took more than 100 years before it was established that the proteins that form intermediate filaments (IFs) comprise a unified protein family, the members of which are ubiquitous in virtually all differentiated cells and present both in the cytoplasm and in the nucleus. However, during the past 2 decades, knowledge regarding the functions of these structures has been expanding rapidly. Many disease-related roles of IFs have been revealed. In some cases, the molecular mechanisms underlying these diseases reflect disturbances in the functions traditionally assigned to IFs, i.e., maintenance of structural and mechanical integrity of cells and tissues. However, many disease conditions seem to link to the nonmechanical functions of IFs, many of which have been defined only in the past few years., Introduction Intermediate filaments (IFs) represent one of the main cytoskeletal systems found in virtually all vertebrate cells. Depending upon the cell type, IFs are composed of different members of the [...]