Linocin and OmpW Are Involved In Attachment Of The Cystic Fibrosis-Associated Pathogen Burkholderia Cepacia Complex To Lung Epithelial Cells and Protect Mice Against Infection

Burkholderia cepacia complex (Bcc) causes chronic opportunistic lung infections in people with cystic fibrosis (CF) resulting in a gradual lung function decline and, ultimately, patient death. Bcc is a complex of eighteen species and is rarely eradicated once a patient is colonised, therefore vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in attachment of Bcc to lung epithelial cells. Fourteen proteins were reproducibly identified by 2-DE from four Bcc strains, representative of two Bcc species: B. cenocepacia, the most virulent and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, Linocin and OmpW. Both proteins were selected based previously published data on these proteins in other species. The E. coli strains expressing recombinant Linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells, compared to control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc colonised CF patients confirmed that both proteins elicit potent humoral responses in vivo. Mice immunised with either recombinant Linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multi-subunit vaccine. Furthermore, it highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens

Compositional control of pore geometry in multivariate metal-organic frameworks: an experimental and computational study

A new approach is reported for tailoring the pore geometry in five series of multivariate metal-organic frameworks (MOFs) based on the structure [Zn-2(bdc)(2)(dabco)] (bdc = 1,4-benzenedicarboxylate, dabco = 1,8-diazabicyclooctane), DMOF-1. A doping procedure has been adopted to form series of MOFs containing varying linker ratios. The series under investigation are [Zn-2(bdc)(2-x)(bdc-Br)(x)(dabco)]center dot nDMF 1 (bdc-Br = 2-bromo-1,4-benzenedicarboxylate), [Zn-2(bdc)(2-x)(bdc-I)(x)(dabco)]center dot nDMF 2 (bdc-I = 2-iodo-1,4-benzenedicarboxylate), [Zn-2(bdc)(2-x)(bdc-NO2)(x)(dabco)]center dot nDMF 3 (bdc-NO2 = 2-nitro-1,4-benzenedicarboxylate), [Zn-2(bdc)(2-x)(bdc-NH2)(x)(dabco)]center dot nDMF 4 (bdc-NH2 = 2-amino-1,4-benzenedicarboxylate) and [Zn-2(bdc-Br)(2-x)(bdc-I)(x)(dabco)] nDMF 5. Series 1-3 demonstrate a functionality-dependent pore geometry transition from the square, open pores of DMOF-1 to rhomboidal, narrow pores with increasing proportion of the 2-substituted bdc linker, with the rhomboidal-pore MOFs also showing a temperature-dependent phase change. In contrast, all members of series 4 and 5 have uniform pore geometries. In series 4 this is a square pore topology, whilst series 5 exhibits the rhomboidal pore form. Computational analyses reveal that the pore size and shape in systems 1 and 2 is altered through non-covalent interactions between the organic linkers within the framework, and that this can be controlled by the ligand functionality and ratio. This approach affords the potential to tailor pore geometry and shape within MOFs through judicious choice of ligand ratios

Shiga Toxin–Producing Escherichia coli Infections Associated with Hemolytic Uremic Syndrome, Italy, 1988–2000

The mean annual incidence of hemolytic uremic syndrome in persons <15 years of age in Italy from 1988 to 2000 was 0.28 per 100,000 population. Laboratory investigations showed that Shiga toxin–producing Escherichia coli (STEC) infection occurred in 73.1% of patients. STEC O157 was the most common serotype, but a considerable number of cases were from infections by non-O157 STEC

The synthesis, structures and reactions of zinc and cobalt metal-organic frameworks incorporating an alkyne-based dicarboxylate linker

The reaction of zinc(II) nitrate and 4,4′-ethynylenedibenzoic acid (H2edb) in DMF at 80 °C gave the metal–organic framework material [Zn4O(edb)3(H2O)2]·6DMF 1 in which edb ligands connect Zn4O centres into a doubly-interpenetrated cubic network with a similar topology to observed with other linear dicarboxylates in the IRMOF series. Analysis of the nitrogen isotherm revealed the material to have a BET surface area of 1088 m2 g−1, which is approximately one-third of the value calculated from GCMC simulations, suggesting incomplete activation or pore blocking in the activated material. The reaction of cobalt(II) nitrate and H2edb in DMF gave [Co3(edb)3(DMF)4]·2.6DMF 2. The structure of 2 is based on Co3(O2CR)6 linear secondary building units that are linked by the edb ligands into a two-dimensional network. When 2 was placed under vacuum, a colour change from pale pink to deep blue was observed, which is consistent with loss of the coordinated DMF molecules. When treated with [Co2(CO)8], crystals of 1 turned dark red, and IR analysis is consistent with coordination of Co2(CO)6 fragments to the alkyne groups. However, the colour change was restricted to the external crystal surfaces. This is a likely consequence of partial framework collapse, which occurs following coordination of Co2(CO)6 to the alkyne groups. Coordination changes the preferred angle between carboxylate groups in the edb ligand, which in turn introduces strain into the network

Factors influencing public health engagement in alcohol licensing in England and Scotland including legal and structural differences: comparative interview analysis

Background: Greater availability of alcohol is associated with higher consumption and harms. The legal systems by which premises are licensed to sell alcohol in England and Scotland differ in several ways. The ExILEnS (Exploring the Impact of alcohol Licensing in England and Scotland) study measured public health team (PHT) activity regarding alcohol licensing from 2012-2019 and identified seven differences between England and Scotland in the timing and type of activities undertaken. Objective: To qualitatively describe the seven previously identified differences between Scotland and England in public health approaches to alcohol licensing, and to examine, from the perspective of public health professionals, what factors may explain these differences. Methods: Ninety-four interviews were conducted with 52 professionals from 14 English and 6 Scottish PHTs selected for diversity who had been actively engaging with alcohol licensing. Interviews focused primarily on the nature of their engagement (n=66) and their rationale for the approaches taken (n=28). Interview data were analysed thematically using NVivo. Findings were constructed by discussion across the research team, to describe and explain the differences in practice found. Findings: Diverse legal, practical and other factors appeared to explain the seven differences. (1) Earlier engagement in licensing by Scottish PHTs in 2012/13 may have arisen from differences in the timing of legislative changes giving public health a statutory role and support from Alcohol Focus Scotland. (2) Public Health England provided significant support from 2014 in England, contributing to an increase in activity from that point there. (3) Renewals of statements of licensing policy (SLPs) were required more frequently in Scotland and at the same time for all Licensing Boards, probably explaining greater focus on policy in Scotland. (4) Organizational structures in Scotland, with public health stakeholders spread across several organizations, likely explained greater involvement of senior leaders there. (5) Without a public health objective for licensing, English PHTs felt less confident about making objections to licence applications without other stakeholders such as the police, and instead commonly negotiated conditions on licences with applicants. In contrast, Scottish PHTs felt any direct contact with applicants was inappropriate due to conflicts of interest. (6) With the public health objective in Scotland, PHTs there were more active in making independent objections to licence applications. Further in Scotland, licensing committee meetings are held to consider all new applications regardless of whether objections have been submitted; unlike in England where there was a greater incentive to resolve objections, because then a meeting was not required. (7) Finally Scottish PHTs involved the public more in licensing, partly because of statutory licensing forums there. Conclusion: The alcohol premises licensing systems in England and Scotland differ in important ways including and beyond the lack of a public health objective for licensing in England. These and other differences, including support of national and local bodies, have shaped opportunities for, and the nature of, public health engagement. Further research could examine the relative success of the approaches taken by PHTs and how temporary increases in availability are handled in the two licensing systems

Building resilience to mosquito-borne diseases in the Caribbean.

Small island developing states in the Caribbean are among the most vulnerable countries on the planet to climate variability and climate change. In the last 3 decades, the Caribbean region has undergone frequent and intense heat waves, storms, floods, and droughts. This has had a detrimental impact on population health and well-being, including an increase in infectious disease outbreaks. Recent advances in climate science have enhanced our ability to anticipate hydrometeorological hazards and associated public health challenges. Here, we discuss progress towards bridging the gap between climate science and public health decision-making in the Caribbean to build health system resilience to extreme climatic events. We focus on the development of climate services to help manage mosquito-transmitted disease epidemics. There are numerous areas of ongoing biological research aimed at better understanding the direct and indirect impacts of climate change on the transmission of mosquito-borne diseases. Here, we emphasise additional factors that affect our ability to operationalise this biological understanding. We highlight a lack of financial resources, technical expertise, data sharing, and formalised partnerships between climate and health communities as major limiting factors to developing sustainable climate services for health. Recommendations include investing in integrated climate, health and mosquito surveillance systems, building regional and local human resource capacities, and designing national and regional cross-sectoral policies and national action plans. This will contribute towards achieving the Sustainable Development Goals (SDGs) and maximising regional development partnerships and co-benefits for improved health and well-being in the Caribbean

Hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival

Chronic myeloid leukemia (CML) stem/progenitor cells (SPC) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPC maintain quiescence will help to clarify how they persist during long-term targeted treatment. We have identified a novel BCR-ABL1 protein kinase dependent pathway mediated by the up-regulation of hsa-mir183, the down-regulation of its direct target EGR1 and, as a consequence, up-regulation of E2F1. We show here that inhibition of hsa-mir183 reduced proliferation and impaired colony formation of CML SPC. Downstream of this, inhibition of E2F1 also reduced proliferation of CML SPC, leading to p53-mediated apoptosis. In addition, we demonstrate that E2F1 plays a pivotal role in regulating CML SPC proliferation status. Thus, for the first time, we highlight the mechanism of hsa-mir183/EGR1-mediated E2F1 regulation and demonstrate this axis as a novel, critical factor for CML SPC survival, offering new insights into leukemic stem cell eradication

National Outbreak of Salmonella Serotype Saintpaul Infections: Importance of Texas Restaurant Investigations in Implicating Jalapeño Peppers

BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination