Effects of passive smoking on children health

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An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Grape Seed Proanthocyanidins Inhibit Melanoma Cell Invasiveness by Reduction of PGE2 Synthesis and Reversal of Epithelial-to-Mesenchymal Transition

Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of grape seed proanthocyanidins (GSPs) on melanoma cancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t. Using in vitro cell invasion assays, we observed that treatment of A375 and Hs294t cells with GSPs resulted in a concentration-dependent inhibition of invasion or cell migration of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2 expression and prostaglandin (PG) E2 production. Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of melanoma cells with COX-2 small interfering RNA, also inhibited melanoma cell migration. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate, an inducer of COX-2, enhanced the phosphorylation of ERK1/2, a protein of mitogen-activated protein kinase family, and subsequently cell migration whereas both GSPs and celecoxib significantly inhibited 12-O-tetradecanoylphorbol-13-acetate -promoted cell migration as well as phosphorylation of ERK1/2. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the migration of melanoma cells. Further, GSPs inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Additionally, inhibition of melanoma cell migration by GSPs was associated with reversal of epithelial-mesenchymal transition process, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin and cytokeratins) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in melanoma cells. Together, these results indicate that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition

Health research prioritization in Somalia: setting the agenda for context specific knowledge to advance universal health coverage

IntroductionDespite recognition that health research is an imperative to progress toward universal health coverage, resources for health research are limited. Yet, especially in sub-Saharan Africa, more than 85% of the resources available for health research are spent on answering less relevant research questions. This misalignment is partially due to absence of locally determined health research priorities. In this study, we identified health research priorities which, if implemented, can inform local interventions required to accelerate progress toward universal health coverage in Somalia.MethodsWe adapted the child health and nutrition research initiative method for research priority setting and applied it in 4 major phases: (1) establishment of an exercise management team, (2) a web-based survey among 84 respondents to identify health research questions; (3) categorization of identified health research questions; and (4) a workshop with 42 participants to score and rank the identified health research questions. Ethical approval was received from ethics review committee of the London School of Hygiene and Tropical Medicine (Ref:26524) and the Somali Research and Development Institute (Ref: EA0143).ResultsTwo hundred and thirty-one unique health research questions were identified and categorized under health systems, services and social determinants (77), communicable diseases (54), non-communicable diseases (41) and reproductive, maternal, new-born, child, adolescent health and nutrition (59). A priority score ranging from 1 to 9 was assigned to each of the questions. For each category, a list of 10 questions with the highest priority scores was developed. Across the four categories, an overall list of 10 questions with the highest priority scores was also developed. These related to bottlenecks to accessing essential health services, use of evidence in decision making, antimicrobial resistance, distribution and risk factors for non-communicable diseases, post-traumatic stress disorder and factors associated with low antenatal care attendance among others.Conclusion and recommendationsThe developed priority research questions can be used to focus health research and to inform appropriation of health research resources to questions that contribute to generation of local health system knowledge which is required to accelerate progress toward universal health coverage in Somalia. The Somalia national institute of health should set up a consortium for provision of technical and financial support for research addressing the identified priority research questions, establish a mechanism to continuously monitor the extent to which new health interventions in Somalia are informed by knowledge generated through conducting prioritized health research and prioritize interventions aimed at strengthening the broader national health research system for Somalia

Soil stabilization with lime for the construction of forest roads

The mechanical performance of soil stabilization using lime to improve forest roads was assessed. This study was conducted with lateritic soil (LVAd30) using lime content of 2% in the municipality of Niquelândia, Goiás state, Brazil. Geotechnical tests of soil characterization, compaction, and mechanical strength were performed applying different compaction efforts and curing periods. The results showed that lime content significantly changed the mechanical performance of natural soil, increasing its mechanical strength and load-carrying capacity. Compaction effort and curing time provided different responses in the unconfined compressive strength (UCS) and California Bearing Ratio (CBR) tests. The best UCS value (786.59 kPa) for the soil-lime mixture was achieved with modified compaction effort and curing time of 28 days. In the CBR test, soil-lime mixtures compacted at intermediate and modified efforts and cured for 28 days were considered for application as subbase material of flexible road pavements, being a promising alternative for use in layers of forest roads

Functionally Redundant RXLR Effectors from <em>Phytophthora infestans</em> Act at Different Steps to Suppress Early flg22-Triggered Immunity

Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs), the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI), significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc) in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the molecular mechanisms underlying the manipulation of host MAMP-triggered immunity (MTI) by P. infestans and to understand the basis of host versus non-host resistance in plants towards P. infestans

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Progress and experiences of implementing an integrated disease surveillance and response system in Somalia; 2016–2023

IntroductionIn 2021, a regional strategy for integrated disease surveillance was adopted by member states of the World Health Organization Eastern Mediterranean Region. But before then, member states including Somalia had made progress in integration of their disease surveillance systems. We report on the progress and experiences of implementing an integrated disease surveillance and response system in Somalia between 2016 and 2023.MethodsWe reviewed 20 operational documents and identified key integrated disease surveillance and response system (IDSRS) actions/processes implemented between 2016 and 2023. We verified these through an anonymized online survey. The survey respondents also assessed Somalia’s IDSRS implementation progress using a standard IDS monitoring framework Finally, we interviewed 8 key informants to explore factors to which the current IDSRS implementation progress is attributed.ResultsBetween 2016 and 2023, 7 key IDSRS actions/processes were implemented including: establishment of high-level commitment; development of a 3-year operational plan; development of a coordination mechanism; configuring the District Health Information Software to support implementation among others. IDSRS implementation progress ranged from 15% for financing to 78% for tools. Reasons for the progress were summarized under 6 thematic areas; understanding frustrations with the current surveillance system; the opportunity occasioned by COVID-19; mainstreaming IDSRS in strategic documents; establishment of an oversight mechanism; staggering implementation of key activities over a reasonable length of time and being flexible about pre-determined timelines.DiscussionFrom 2016 to 2023, Somalia registered significant progress towards implementation of IDSRS. The 15 years of EWARN implementation in Somalia (since 2008) provided a strong foundation for IDSRS implementation. If implemented comprehensively, IDSRS will accelerate country progress toward establishment of IHR core capacities. Sustainable funding is the major challenge towards IDSRS implementation in Somalia. Government and its partners need to exploit feasible options for sustainable investment in integrated disease surveillance and response