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Cytoplasmic incompatibility (CI) is the most common symbiont-induced reproductive manipulation. Specifically, symbiont-induced sperm modifications cause catastrophic mitotic defects in the fertilized embryo and ensuing lethality in crosses between symbiotic males and either aposymbiotic females or females harboring a different symbiont strain. However, if the female carries the same symbiont strain, then embryos develop properly, thereby imparting a relative fitness benefit to symbiont-transmitting mothers. Thus, CI drives maternally-transmitted bacteria to high frequencies in arthropods worldwide. In the past two decades, CI experienced a boom in interest due to its (i) deployment in worldwide efforts to curb mosquito-borne diseases, (ii) causation by bacteriophage genes, cifA and cifB, that modify sexual reproduction, and (iii) important impacts on arthropod speciation. This review serves as a gateway to experimental, conceptual, and quantitative themes of CI and outlines significant gaps in understanding CI's mechanism that are ripe for investigation from diverse subdisciplines in the life sciences.Matriglycan [-GlcA-β1,3-Xyl-α1,3-]n serves as a scaffold in many tissues for extracellular matrix proteins containing laminin-G domains including laminin, agrin, and perlecan. Like-acetyl-glucosaminyltransferase 1 (LARGE1) synthesizes and extends matriglycan on α-dystroglycan (α-DG) during skeletal muscle differentiation and regeneration; however, the mechanisms which regulate matriglycan elongation are unknown. Here, we show that Protein O-Mannose Kinase (POMK), which phosphorylates mannose of core M3 (GalNAc-β1,3-GlcNAc-β1,4-Man) preceding matriglycan synthesis, is required for LARGE1-mediated generation of full-length matriglycan on α-DG (~150 kDa). In the absence of Pomk gene expression in mouse skeletal muscle, LARGE1 synthesizes a very short matriglycan resulting in a ~ 90 kDa α-DG which binds laminin but cannot prevent eccentric contraction-induced force loss or muscle pathology. Solution NMR spectroscopy studies demonstrate that LARGE1 directly interacts with core M3 and binds preferentially to the phosphorylated form. Collectively, our study demonstrates that phosphorylation of core M3 by POMK enables LARGE1 to elongate matriglycan on α-DG, thereby preventing muscular dystrophy.Phosphatidylinositol 3-phosphate (PI(3)P) levels in Plasmodium falciparum correlate with tolerance to cellular stresses caused by artemisinin and environmental factors. However, PI(3)P function during the Plasmodium stress response was unknown. Here, we used PI3K inhibitors and antimalarial agents to examine the importance of PI(3)P under thermal conditions recapitulating malarial fever. Live cell microscopy using chemical and genetic reporters revealed that PI(3)P stabilizes the digestive vacuole (DV) under heat stress. We demonstrate that heat-induced DV destabilization in PI(3)P-deficient P. falciparum precedes cell death and is reversible after withdrawal of the stress condition and the PI3K inhibitor. A chemoproteomic approach identified PfHsp70-1 as a PI(3)P-binding protein. An Hsp70 inhibitor and knockdown of PfHsp70-1 phenocopy PI(3)P-deficient parasites under heat shock. Furthermore, PfHsp70-1 downregulation hypersensitizes parasites to heat shock and PI3K inhibitors. Our findings underscore a mechanistic link between PI(3)P and PfHsp70-1 and present a novel PI(3)P function in DV stabilization during heat stress.
Research from tobacco and alcohol markets suggests advertising exposure is associated with perceptions of lower risk and increased use among young people. Limiting marketing may be a regulatory approach to prevent potential negative effects of retail marijuana legalization on youth use. This study assessed marijuana advertising exposure reported by youths in Oregon after the start of retail marijuana sales in October 2015.
Data from a 2017 school-based survey of Oregon 8th (N = 14,852) and 11th (N = 11,895) graders were used to characterize marijuana advertising exposure. Subgroup differences in reported exposure were assessed by using Pearson χ
tests and multiple logistic regression.
About three-quarters of 8th (72.2%) and 11th graders (78.1%) in Oregon reported seeing marijuana advertising in the past month. Youths most frequently reported seeing advertising on storefronts and online, and odds of exposure were significantly higher for girls; lesbian, gay, or bisexual youths; current marijuana users; purview of state authority (eg, billboards, storefronts) depending on state-specific interpretation of free speech protections.
The human papillomavirus (HPV) increases the risk for cancers of the cervix, oropharynx, vulva, vagina, penis, and anus. HPV vaccination rates are low in many states having large medically underserved areas. In such areas, school nurses are a potential partner for improving population health, but their perceptions about HPV, HPV vaccination, and their role in promoting HPV vaccination have not been well documented.
We administered a cross-sectional survey to 61 of 74 lead school nurses at their 2019 annual training session in South Carolina. Survey questions assessed lead school nurses' HPV vaccination beliefs, barriers, and HPV vaccination role in schools. We tabulated descriptive data and created heat maps to visualize correlations between responses.
Despite 95.1% of nurses envisioning a role in supporting HPV vaccination at their schools, only 41.0% envisioned an active role in promoting HPV vaccine among students. Lead nurses consistently believed in vaccinating both male and female students; in vaccine safety, effectiveness, and health benefits; and in recommending HPV vaccination. The nurses agreed that lack of time and competing priorities were barriers to HPV vaccination. Few other barriers were consistently identified.
Partnering with school nurses may be a feasible strategy to overcome barriers to increasing HPV vaccination rates in medically underserved areas. However, to increase nurses' confidence and time allotment to assume an active role in HPV vaccine promotion in their schools, coordinated and sustained partnerships between public health agencies, school districts, and school nurses are needed.
Partnering with school nurses may be a feasible strategy to overcome barriers to increasing HPV vaccination rates in medically underserved areas. However, to increase nurses' confidence and time allotment to assume an active role in HPV vaccine promotion in their schools, coordinated and sustained partnerships between public health agencies, school districts, and school nurses are needed.
Medication adherence can improve hypertension management. How blood pressure medications are prescribed and purchased can promote or impede adherence.
We used comprehensive dispensing data on prescription blood pressure medication from Symphony Health's 2017 Integrated Dataverse to assess how prescription- and payment-related factors that promote medication adherence (ie, fixed-dose combinations, generic formulations, mail order, low-cost or no-copay medications) vary across US states and census regions and across the market segments (grouped by patient age, prescriber type, and payer type) responsible for the greatest number of blood pressure medication fills.
In 2017, 706.5 million prescriptions for blood pressure medication were filled, accounting for $29.0 billion in total spending (17.0% incurred by patients). As a proportion of all fills, factors that promoted adherence varied by state fixed-dose combinations (from 5.8% in Maine to 17.9% in Mississippi); generic formulations (from 95.2% in New Jer blood pressure medication adherence may increase adherence and improve hypertension management.Non-human primates form an important animal model for the evaluation of immunogenicity and efficacy of novel 'universal' vaccine candidates against influenza virus. However, in most studies a combination of intra-tracheal or intra-bronchial, oral and nasal virus inoculation is used with a standard virus dose of between 1 and 10 million tissue culture infective doses, which differs from typical modes of virus exposure in humans. This paper studies the systemic and local inflammatory and immune effects of aerosolized versus combined-route exposure to pandemic H1N1 influenza virus. In agreement with a previous study, both combined-route and aerosol exposure resulted in similar levels of virus replication in nose, throat and lung lavages. However, the acute release of pro-inflammatory cytokines and chemokines, acute monocyte activation in peripheral blood as well as increased cytokine production and T-cell proliferation in the lungs were only observed after combined-route infection and not after aerosol exposure. Longitudinal evaluation by computed tomography demonstrated persistence of lung lesions after resolution of the infection and a tendency for more lesions in the lower lung lobes after combined-route exposure versus upper and middle lung lobes after aerosol exposure. Computed tomography scores were observed to correlate with fever. In conclusion, influenza virus infection by aerosol exposure is accompanied by less immune-activation and inflammation in comparison with direct virus installation, despite similar levels of virus replication and development of lesions in the lungs.Clostridium perfringens is associated with a variety of diseases in both humans and animals. Recent advances in genomic sequencing make it timely to re-visit this important pathogen. Although the genome sequence of C. perfringens was first determined in 2002, large-scale comparative genomics with isolates of different origins is still lacking. In this study, we used whole-genome sequencing of 45 C. perfringens isolates with isolation time spanning an 80-year period and performed comparative analysis of 173 genomes from worldwide strains. We also conducted phylogenetic lineage analysis and introduced an openness index (OI) to evaluate the openness of bacterial genomes. We classified all these genomes into five lineages and hypothesized that the origin of C. perfringens dates back to ~80 000 years ago. We showed that the pangenome of the 173 C. perfringens strains contained a total of 26 954 genes, while the core genome comprised 1020 genes, accounting for about a third of the genome of each isolate. We demonst of worldwide strains.Although several studies have investigated genetic diversity of Leishmania infantum in North Africa, genome-wide analyses are lacking. Here, we conducted comparative analyses of nuclear and mitochondrial genomes of seven L. infantum isolates from Tunisia with the aim to gain insight into factors that drive genomic and phenotypic adaptation. SMIFH2 Isolates were from cured (n=4) and recurrent (n=3) visceral leishmaniasis (VL) cases, originating from northern (n=2) and central (n=5) Tunisia, where respectively stable and emerging VL foci are observed. All isolates from relapsed patients were from Kairouan governorate (Centre); one showing resistance to the anti-leishmanial drug Meglumine antimoniate. Nuclear genome diversity of the isolates was analysed by comparison to the L. infantum JPCM5 reference genome. Kinetoplast maxi and minicircle sequences (1 and 59, respectively) were extracted from unmapped reads and identified by blast analysis against public data sets. The genome variation analysis grouped together isolates from the same geographical origins.
Homepage: https://www.selleckchem.com/products/smifh2.html
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