Search

Lymphatic vessels grow through active sprouting and mature into a vascular complex that includes lymphatic capillaries and collecting vessels that ensure fluid transport. However, the signaling cues that direct lymphatic sprouting and patterning remain unclear. In this study, we demonstrate that chemokine signaling, specifically through CXCL12 and CXCR4, plays crucial roles in regulating lymphatic development. We show that LEC-specific Cxcr4-deficient mouse embryos and CXCL12 mutant embryos exhibit severe defects in lymphatic sprouting, migration and lymphatic valve formation. We also discovered that CXCL12, originating from peripheral nerves, directs the migration of dermal lymphatic vessels to align with nerves in developing skin. Deletion of Cxcr4 or blockage of CXCL12 and CXCR4 activity results in reduced VEGFR3 levels on the LEC surface. This, in turn, impairs VEGFC-mediated VEGFR3 signaling and downstream PI3K and AKT activities. Taken together, these data identify previously unknown chemokine signaling originating from peripheral nerves that guides dermal lymphatic sprouting and patterning. Our work identifies for the first time a neuro-lymphatics communication during mouse development and reveals a previously unreported mechanism by which CXCR4 modulates VEGFC, VEGFR3 and AKT signaling. [ABSTRACT FROM AUTHOR]

Aortic stenosis (AS) is the most common valvular heart disease in developed countries, and its prevalence is higher in older patients. Clinical studies have shown gender disparity in the pathogenesis and the progression of aortic stenosis. This disparity has led to several overwhelming questions regarding its impact on the clinical outcomes and treatment of the disease and the requirement of personalized sex-specific approaches for its management. Indeed, aortic stenosis differs in the pathophysiological response to pressure overload created by the stenosis in women compared to men, which would translate into differences in cardiac remodeling and clinical outcomes. Several studies have focused on understanding the differences regarding disease progression according to biological gender and have found that sex hormones play a crucial role. Sex hormones affect many metabolic processes, thus activating crucial cell signaling and energy metabolism through mitochondrial activity. Yet, there is still a significant gap in knowledge on how biological sex influences the pathophysiology of AS. In this review, we have discussed studies that point to the role of sex-related physiological differences in the molecular pathways and the clinical presentation of the disease and outcome in women and men. We used the format of narrative review to review and summarize the body of literature without being systematic but with taking great care of considering the most impactful data available to date on the topic, especially randomized trials, metanalyses, and prospective studies and registries when available, as well as experimental studies with rigorous methodological approaches regarding the basic mechanisms and pathophysiology of the disease in women compared to men. The opinion of the authors on a particular issue or finding was expressed when appropriate for clarification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Arboviruses are controlled through insecticide control of their mosquito vector. However, inconsiderate use of insecticides often results in the selection of resistance in treated populations, so that monitoring is required to optimize their usage. Here, Culex pipiens (West Nile and Rift Valley Fever virus vector) specimens were collected from four Moroccan cities. Levels of susceptibility to the organophosphate (OP) insecticide malathion were assessed using World Health Organization (WHO)‐recommended bioassays. Individual mosquitoes were tested for the presence of the G119S mutation in the ace‐1 gene, the main OP‐target resistance mutation. RESULTS: Bioassays showed that mosquitoes from Mohammedia were significantly more resistant to malathion than those from Marrakech. Analyzing the ace‐1 genotypes in dead and surviving individuals suggested that other resistance mechanisms may be present in Mohammedia. The ace‐1 resistance allele frequencies were relatively moderate (< 0.4). Their analyses in three Moroccan cities (Tangier, Casablanca and Marrakech) however showed disparities between two coexisting Cx. pipiens forms and revealed that the G119S mutation tends to be more frequent in urban than in rural collection sites. CONCLUSION: These findings provide a reference assessment of OP resistance in Morocco and should help the health authorities to develop informed and sustainable vector control programs. © 2018 Society of Chemical Industry Recurrent vector control selects for insecticide resistance. This article presents an evaluation of target‐mutation resistance to organophosphate insecticides in the Culex pipiens complex in Morocco, and its relation to urbanization. [ABSTRACT FROM AUTHOR]