Proteomic analysis of a murine model of lung hypoplasia induced by oligohydramnios

Acknowledgments This work was supported by funding from the National Institute of General Medical Sciences of the National Institutes of Health, Number: P30GM114750 and Oh–Zopfi Grant for Perinatal Research, Department of Pediatrics; Kilguss Research Core at Women & Infants Hospital of Rhode Island. Funding information National Institute of General Medical Sciences, Grant/Award Number: 30GM114750; Oh–Zopfi Award for Perinatal Research, Women & Infants Hospital of Rhode IslandPeer reviewedPostprin

Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells

Acknowledgments This work was supported from the National Institute of Health (NIGMS grant Number P30GM114750 & P30GM103410, NCRR grant Numbers P30RR031153, P20RR018728 & S10RR02763); National Science Foundation (EPSCoR grant No 0554548); Oh–Zopfi for Perinatal Research Award, Women & Infants Hospital of Rhode Island. We thank Brenda Vecchio for her support in manuscript formatting and Quanfu Mao for his support to use the instruments.Peer reviewedPostprin

Oligohydramnios compromises lung cells size and interferes with epithelial–endothelial development

Funded by National Institute of General Medical Sciences of the National Institutes of Health. Grant Number: P30GM114750 Department of Pediatrics Kilguss Research Core of Women & Infants Hospital of Rhode IslandPeer reviewedPostprin

Immunization with PfGBP130 generates antibodies that inhibit RBC invasion by P. falciparum parasites

BackgroundDespite decades of effort, Plasmodium falciparum malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions.Methods and resultsTo discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to P. falciparum infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111–374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion in vitro. mRNA encoding the full ectodomain of PfGBP130 (aa 89–824) also generated parasite growth-inhibitory antibodies.ConclusionWe are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates

Sexuality, rights and personhood: tensions in a transnational world

<p>Abstract</p> <p>Background</p> <p>This article discusses what happens when normative ‘global’ discourses of rights and individuated sexual identity confront the messiness of ‘local’ realities. It considers the tensions that emerge when the relationship between sexual and social identities is not obvious and the implications of such tensions for public health and sexual rights activism. These questions are addressed through debates over the naming of male-to-male sexualities and desires in the context of globalization and the growth of a large NGO (non-governmental organization) sector in urban Bangladesh.</p> <p>Methods</p> <p>The material in the paper draws on a research project undertaken in 2008-9 in Dhaka, Bangladesh. A fundamental objective was to produce a contextualized understanding of sexuality in Dhaka city. Methods used included structured interviews, focus group discussions and informal conversations with a range of participants (students, factory workers, public health professionals and sexual minorities). The aim was to generate a conceptual and analytical framework around sexuality and rights rather than to undertake an empirical survey of any one population.</p> <p>Results</p> <p>As descriptors, globalized identity categories such as Men who have Sex with Men (MSM), used by public health providers, the state and donors; and gay/lesbian, invoked by human rights activists and transnational NGOs, are too narrow to capture the fluid and highly context-specific ways in which gender and sexually nonconforming persons understand themselves in Bangladesh. Further, class position mediates to a significant degree the reception, appropriation or rejection of transnational categories such as MSM and Lesbian, Gay, Bisexual, Transgender (LGBT). The tension is reflected in the sometimes fraught relations between service providers to MSM, the people they serve and an emerging group who identify as LGBT.</p> <p>Conclusion</p> <p>A simple politics of recognition will be inadequate to the task of promoting health and human rights for all; such a strategy would effectively exclude individuals who do not necessarily connect their sexual practices with a specific sexual or social identity.</p

Unexpected Role for Helicobacter pylori DNA Polymerase I As a Source of Genetic Variability

Helicobacter pylori, a human pathogen infecting about half of the world population, is characterised by its large intraspecies variability. Its genome plasticity has been invoked as the basis for its high adaptation capacity. Consistent with its small genome, H. pylori possesses only two bona fide DNA polymerases, Pol I and the replicative Pol III, lacking homologues of translesion synthesis DNA polymerases. Bacterial DNA polymerases I are implicated both in normal DNA replication and in DNA repair. We report that H. pylori DNA Pol I 5′- 3′ exonuclease domain is essential for viability, probably through its involvement in DNA replication. We show here that, despite the fact that it also plays crucial roles in DNA repair, Pol I contributes to genomic instability. Indeed, strains defective in the DNA polymerase activity of the protein, although sensitive to genotoxic agents, display reduced mutation frequencies. Conversely, overexpression of Pol I leads to a hypermutator phenotype. Although the purified protein displays an intrinsic fidelity during replication of undamaged DNA, it lacks a proofreading activity, allowing it to efficiently elongate mismatched primers and perform mutagenic translesion synthesis. In agreement with this finding, we show that the spontaneous mutator phenotype of a strain deficient in the removal of oxidised pyrimidines from the genome is in part dependent on the presence of an active DNA Pol I. This study provides evidence for an unexpected role of DNA polymerase I in generating genomic plasticity

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points