Rainfall risk over the city of Abidjan (Côte d'Ivoire): first contribution of the joint analysis of daily rainfall from a historical record and a recent network of rain gauges

Every year, rains cause material damage and human losses, in Abidjan (Côte d'Ivoire). The objective of this study is to contribute to the characterization of the rain hazard in the District of Abidjan. The available data are made up of daily rainfall from a historical station “Abidjan airport” (1961–2014) and an academic network of rain gauges (21) progressively implemented in Abidjan since 2015. A descriptive analysis (date of occurrence, rainfall depth, mean wet days intensity and number of rainy days) on the Highest Cumulative Rainfall Periods (HCRP: 60 d) is conducted on the long-term station. The periods of highest risk of flooding during the long and short rainy seasons are characterized. The Experimental variograms of extreme rainfalls derived from the current network, allow to evaluate their extensions according to the rainy season.</p

Evidence for SH2 Domain-Containing 5′-Inositol Phosphatase-2 (SHIP2) Contributing to a Lymphatic Dysfunction

<div><p>The lymphatic vasculature plays a critical role in a number of disease conditions of increasing prevalence, such as autoimmune disorders, obesity, blood vascular diseases, and cancer metastases. Yet, unlike the blood vasculature, the tools available to interrogate the molecular basis of lymphatic dysfunction/disease have been lacking. More recently, investigators have reported that dysregulation of the PI3K pathway is involved in syndromic human diseases that involve abnormal lymphatic vasculatures, but there have been few compelling results that show the direct association of this molecular pathway with lymphatic dysfunction in humans. Using near-infrared fluorescence lymphatic imaging (NIRFLI) to phenotype and next generation sequencing (NGS) for unbiased genetic discovery in a family with non-syndromic lymphatic disease, we discovered a rare, novel mutation in <i>INPPL1</i> that encodes the protein SHIP2, which is a negative regulator of the PI3K pathway, to be associated with lymphatic dysfunction in the family. <i>In vitro</i> interrogation shows that SHIP2 is directly associated with impairment of normal lymphatic endothelial cell (LEC) behavior and that SHIP2 associates with receptors that are associated in lymphedema, implicating its direct involvement in the lymphatic vasculature.</p></div

Identification of T180A SHIP2 mutation in familial lymphedema.

<p>(<b>A</b>) Pedigree of the nucleus and extended family showing affected (filled) and unaffected (open) subjects with lymphedema, phenotyped by NIRF imaging and WES analysis revealing subjects who harbor T180A <i>SHIP2</i>, G315V <i>HGF</i> and N463S <i>MAP3K7</i> mutations. NIRF imaging reveals (<b>B</b>) dermal backflow in medial left ankle of Subject #6 (bilateral lymphedema <i>praecox</i>) and also has abnormal lymphatic capillaries on thigh (not shown). (<b>C</b>) Abnormal lymphatic capillaries radiating from the injection site on the medial left ankle of Subject #9 which were also observed capillaries on the thigh on this unaffected subject. (<b>D</b>) Tortuous lymphatics draining the medial left ankle and lymphatic capillaries radiating from the left medial calf in Subject #12 (unaffected). All three subjects also appeared to have dilated lymphatics.</p

SHIP2 interacts with cMET and with VEGFR3.

<p>Proximity ligation assay (PLA) depicting interaction of (<b>A</b>) SHIP2-FLAG and cMET and (<b>B</b>) SHIP2-FLAG and VEGFR3 in Vector- and FLAG-tagged WT SHIP2-transfected TIME cells following (<b>A</b>) HGF stimulation and (<b>B</b>) VEGFC stimulation and respective quantification of PLA fluorescence signal (<b>C</b> and <b>D</b>) in 100 cells/experiment (N = 3) quantified by ImageJ. (<b>E, F</b>) No statistical difference is seen between WT SHIP2 <i>vs</i>. T180A SHIP2 in their interaction with cMET and with VEGFR3. Quantification of 100 cells/experiment (N = 3). Blue  =  DAPI, green  =  actin and red  =  PLA fluorescence with each red dot depicting <i>in situ</i> interaction site. *<i>p</i><0.05, **<i>p</i><0.01. Scale bar  =  50 µm.</p

Influence of T180A-SHIP2 on LEC functional responses.

<p>(<b>A</b>)Western blot analysis depicting expression of SHIP2 (green) and DYKDDDDK (FLAG) tag epitope (red) in SHIP2-FLAG TIME transfectants. COX IV (red) used to determine equal protein loading. (<b>B</b>) T180A-SHIP2 exhibits reduced migration assessed by wound healing (top panels) and tube formation (bottom panels). (<b>C</b>) WT-SHIP2 exhibits increased chemotaxis compared to Vector in response to HGF while T180A-SHIP2 has slightly reduced, but not significant, chemotaxis towards HGF, compared to WT. Data are presented as % of area covered by migrated cells on underside of transwell filters and cells stained with DRAQ5. (<b>D</b>) WT-SHIP2 exhibits increased adhesion (assessed by crystal violet staining) over Vector on BSA and collagen while T180A-SHIP2 shows decreased adhesion to collagen compared to WT. (<b>E</b>) T180A-SHIP2 results in increased activation of AKT and ERK upon HGF stimulation in comparison to WT-SHIP2. Representative blots shown. Phosphorylation was determined by Western blotting of cell lysates with phosphospecific antibodies. Blots were reprobed with total AKT and ERK antibodies to demonstrate equal loading. Phospho- and total-antibody reprobes were detected with IRDye 680 nm secondary antibodies. Quantification of AKT and ERK activation performed by average mean fluorescence intensity (MFI) of 3 independent experiments and represented as a ratio of pAKT-S473 to total AKT and pERK1/2 to total ERK1/2, respectively. (<b>F</b>) WT-SHIP2 results in less VEGFC-induced PIP3 levels compared to Vector, while T180A has increased PIP3 levels compared to WT and data expressed as fluorescence intensity of PIP3 normalized to 1% FBS in 100 cells/experiment (N = 3). PIP3 levels were assessed by fluorescent immunocytochemistry of 10 min VEGFC-stimulated cells using anti-PIP3 antibody. (<b>G</b>) Malachite green <i>in vitro</i> phosphatase assay indicates no significant difference in amount of phosphate released by T180A SHIP2 over WT-SHIP2 suggesting similar enzymatic activity against recombinant PIP3 substrate. Recombinant SHIP2 (rSHIP2) and PIP3 (rPIP3 only, no enzyme) used as positive and negative controls respectively. Comparisons are between Vector <i>vs</i>. WT; WT <i>vs</i>. T180A and rSHIP2 <i>vs.</i> WT; and rSHIP2 <i>vs.</i> rPIP3 *<i>p</i><0.05, **<i>p</i><0.01, *** <i>p</i><0.001. Scale bar  = 100 µm (<b>B</b>) and 50 µm (<b>C</b> and <b>D</b>) MW =  molecular weight marker.</p