Differential regulation of lymphatic junctional morphology and the potential effects on cardiovascular diseases.

The lymphatic vasculature provides an essential route to drain fluid, macromolecules, and immune cells from the interstitium as lymph, returning it to the bloodstream where the thoracic duct meets the subclavian vein. To ensure functional lymphatic drainage, the lymphatic system contains a complex network of vessels which has differential regulation of unique cell-cell junctions. The lymphatic endothelial cells lining initial lymphatic vessels form permeable "button-like" junctions which allow substances to enter the vessel. Collecting lymphatic vessels form less permeable "zipper-like" junctions which retain lymph within the vessel and prevent leakage. Therefore, sections of the lymphatic bed are differentially permeable, regulated in part by its junctional morphology. In this review, we will discuss our current understanding of regulating lymphatic junctional morphology, highlighting how it relates to lymphatic permeability during development and disease. We will also discuss the effect of alterations in lymphatic permeability on efficient lymphatic flux in health and how it may affect cardiovascular diseases, with a focus on atherosclerosis.

G119S ace-1 mutation conferring insecticide resistance detected in the Culex pipiens complex in Morocco.

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.

Insecticide resistance and target site mutations (G119S ace-1 and L1014F kdr) of Culex pipiens in Morocco.

BACKGROUND: Control of the mosquito vector Culex pipiens with insecticides is the main way to control arboviruses that the species can transmit such as West Nile virus (WNV) and Rift Valley fever virus (RVFV). However, its efficiency has been hampered by the emergence of insecticide resistance. Little is known about the insecticide-resistance status and underlying resistance mechanisms of field-collected populations of Cx. pipiens in Morocco. METHODS: Mosquito adults from Mohammadia city in Morocco were reared from immature stages. The level of their susceptibility to insecticides was assessed using standard WHO bioassay. The two forms of the Cx. pipiens complex and their hybrids were identified by a multiplex PCR. Identified mosquitoes were then tested for the presence of the G119S ace-1 and L1014F kdr mutations using PCR-RFLP and PCR assays, respectively. RESULTS: WHO bioassays indicated that Cx. pipiens was resistant to all tested insecticides: lambda-cyhalothrin (49% mortality), permethrin (63% mortality), DDT (16% mortality), malation (52% mortality) and bendiocarb (39% mortality). The frequency of the 119S allele was almost identical in the pipiens form and hybrids (0.11 and 0.15, respectively) whereas it remained low in the molestus form (0.03). No significant correlation was observed between the G119S allele and the resistance phenotype to two tested insecticides (malathion and bendiocarb). The frequency of the L1014F allele was identical in the pipiens form and hybrids (0.44) whereas it was low in the molestus form (0.36) but no significant difference was detected (χ2 = 1.46, df = 1, P = 0.225). The presence of the L1014F kdr mutation was significantly associated with resistance to three tested insecticides in pipiens form (P = 0.0019, P = 0.0023 and P = 0.023, respectively, to lambda-cyhalothrin, permethrin and DDT) whereas no significant correlation was observed between the L1014F kdr mutation and resistance phenotype in molestus form and hybrids to the three tested insecticides. CONCLUSION: These findings showed that wild populations of Cx. pipiens have developed resistance against the main insecticide families with different modes of action: organochlorines (DDT), organophosphates (malathion), carbamates (bendiocarb), pyrethroids (lambda-cyhalothrin, permethrin). Therefore, urgent action should be taken to manage the resistance in this species to maintain the effectiveness of arbovirus control.

First report of L1014F-kdr mutation in Culex pipiens complex from Morocco.

BACKGROUND: Mosquitoes of the Culex pipiens complex, competent vectors for West Nile virus (WNV) and Rift Valley fever virus (RVFV) are widely targeted by insecticide treatments. The intensive application of chemical insecticides led to the development of resistance in many insects including Culex pipiens mosquitoes. The absence of data on resistance mechanisms in Morocco allow us to assess the levels of lambda-cyhalothrin resistance and the frequency of the mutated gene L1014F kdr in different forms of Cx. pipiens complex from three regions of Morocco. METHODS: Mosquito adults were reared from immature stages collected in three different regions in Morocco (Tangier, Casablanca and Marrakech). Standard WHO insecticide susceptibility tests were conducted on adults emerged from collected larvae. Specimens were identified as belonging to the Culex pipiens complex using a multiplex PCR assay with diagnostic primers designed from the flanking region of microsatellite CQ11. Identified mosquitoes were then tested for the presence of the L1014F kdr mutation using PCR assay. RESULTS: Our results showed that 21% of the tested population has a resistance to lambda-cyhalothrin. The molecular identification of survivors shows that 43% belonged to the Cx. pipiens pipiens and only 9.5% to the Cx. pipiens molestus form. On the other hand, 416 specimens were screened for the L1014F kdr mutation. L1014F mutation was detected in different forms of Cx. pipiens in different sites. The frequency of L1014F mutation was similar between the Cx. pipiens pipiens form and hybrid form, while it was lower in the Cx. pipiens molestus form. The presence of the L1014F kdr allele was significantly associated with resistance to lambda-cyhalothrin in Cx. pipiens pipiens (P < 0.0001) and hybrid form (P < 0.0001). CONCLUSION: Resistance to lambda-cyhalothrin of Cx. pipiens populations appears to be largely due to the L1014F kdr mutation. To our knowledge, the frequencies of L1014F kdr mutation are examined for the first time in natural populations of the Culex pipiens complex in Morocco. These findings will provide important information to propose more adapted vector control measures towards this mosquito species, potential vector of arboviruses.