CLIMATE RISK AND FOOD SECURITY IN MALI

We combine socioeconomic data from a large‐scale household survey with historical climate data to map the climate sensitivity of availability and access dimensions of food security in Mali, and infer the ways in which at‐risk communities may have been impacted by persistent climatic shift. Thirty years after 1982–1984, the period of most intense drought during the protracted late 20th century drying of the Sahel, the impact of drought on livelihoods and food security is still recognizable in the Sahelian center of Mali. This impact is expressed in the larger fraction of households in this Sahelian center of the country—the agro‐ecological transition between pastoralism in the north, and sedentary agriculture in the south—who practice agriculture but not livestock raising, despite environmental conditions that are suitable to their combination. These households have lower food security and rely more frequently on detrimental nutrition‐based coping strategies, such as reducing the quantity or quality of meals. In contrast, the more food secure households show a clear tendency toward livelihood diversification away from subsistence agriculture. These households produce less of what they consume, yet spend less on food in proportion. The analysis points to the value of interdisciplinary research—in this case bridging climate science and vulnerability analysis—to gain a dynamical understanding of complex systems, understanding which may be exploited to address real‐world challenges, offering lessons about food security and local adaptation strategies in places among the most vulnerable to climate

Pharmaco-régulation de la progression tumorale de cancers mammaires par des oligosaccharides de lambda carraghénanes inhibiteurs d’héparanase

Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodeling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumor mechanisms. Given they have their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine Symbol-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated using shRNA strategy. We showed neither cytotoxic nor proliferative effects of our inhibitor candidates but λ-CO was the most efficient to reduce cell migration and invasion compared with heparins and that, in a HPSE dependent-manner. We evidenced that λ-CO tightly controlled a HPSE/MMP14/MMP-2 axis leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE “modulator” capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.Des molécules à base de sucre telles que les héparines ou les polysaccharides d'héparane sulfate naturels ont été développées et largement étudiées pour contrôler l'activité enzymatique de l'héparanase (HPSE), acteur clé du remodelage de la matrice extracellulaire au cours de la pathogenèse du cancer. Cependant, des fonctions non enzymatiques de l'HPSE ont également été décrites dans les mécanismes tumoraux. Compte tenu de leurs propriétés polyvalentes, nous avons émis l'hypothèse que les inhibiteurs à base de sucre peuvent interférer avec les activités enzymatiques mais aussi non enzymatiques de l’HPSE. Dans ce travail, nous avons évalué les effets d'un oligosaccharide marin original dérivé du carraghénane-λ (CO-λ) que nous avons décrit précédemment, ainsi que ceux de son homologue natif et des héparines, sur la viabilité cellulaire, la prolifération, la migration et l'invasion des cellules cancéreuses du sein, MDA-MB- 231, mais aussi des cellules sh-MDA-MB231, dans lesquelles l'expression de l’HPSE a été sélectivement régulée à la baisse en utilisant la stratégie shRNA. Nous n'avons montré aucun effet cytotoxique ni prolifératif de nos candidats inhibiteurs, mais le CO-λ était le plus efficace pour réduire la migration et l'invasion cellulaire par rapport aux héparines et ce, de manière HPSE dépendante. Nous avons mis en évidence que le CO-λ contrôlait étroitement un axe HPSE/MMP-14/MMP-2 conduisant à une activité MMP-2 réduite. Au final, cette étude met en évidence que le CO-λ est un puissant « modulateur » de l'HPSE capable de réduire non seulement l'activité enzymatique de l'HPSE mais également les fonctions contrôlées par les niveaux d'HPSE

Pharmaco-régulation de la progression tumorale de cancers mammaires par des oligosaccharides de lambda carraghénanes inhibiteurs d’héparanase

Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodeling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumor mechanisms. Given they have their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine Symbol-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated using shRNA strategy. We showed neither cytotoxic nor proliferative effects of our inhibitor candidates but λ-CO was the most efficient to reduce cell migration and invasion compared with heparins and that, in a HPSE dependent-manner. We evidenced that λ-CO tightly controlled a HPSE/MMP14/MMP-2 axis leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE “modulator” capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.Des molécules à base de sucre telles que les héparines ou les polysaccharides d'héparane sulfate naturels ont été développées et largement étudiées pour contrôler l'activité enzymatique de l'héparanase (HPSE), acteur clé du remodelage de la matrice extracellulaire au cours de la pathogenèse du cancer. Cependant, des fonctions non enzymatiques de l'HPSE ont également été décrites dans les mécanismes tumoraux. Compte tenu de leurs propriétés polyvalentes, nous avons émis l'hypothèse que les inhibiteurs à base de sucre peuvent interférer avec les activités enzymatiques mais aussi non enzymatiques de l’HPSE. Dans ce travail, nous avons évalué les effets d'un oligosaccharide marin original dérivé du carraghénane-λ (CO-λ) que nous avons décrit précédemment, ainsi que ceux de son homologue natif et des héparines, sur la viabilité cellulaire, la prolifération, la migration et l'invasion des cellules cancéreuses du sein, MDA-MB- 231, mais aussi des cellules sh-MDA-MB231, dans lesquelles l'expression de l’HPSE a été sélectivement régulée à la baisse en utilisant la stratégie shRNA. Nous n'avons montré aucun effet cytotoxique ni prolifératif de nos candidats inhibiteurs, mais le CO-λ était le plus efficace pour réduire la migration et l'invasion cellulaire par rapport aux héparines et ce, de manière HPSE dépendante. Nous avons mis en évidence que le CO-λ contrôlait étroitement un axe HPSE/MMP-14/MMP-2 conduisant à une activité MMP-2 réduite. Au final, cette étude met en évidence que le CO-λ est un puissant « modulateur » de l'HPSE capable de réduire non seulement l'activité enzymatique de l'HPSE mais également les fonctions contrôlées par les niveaux d'HPSE

Organisation des pontes de dinosauriens de la parafamille des Megaloolithidae Zhao, 1979

PARIS-Museum Hist.Naturelle (751052304) / SudocSudocFranceF

El Niño and other climatic drivers of epidemic malaria in Ethiopia: new tools for national health adaptation plans

Abstract Background Ethiopia has a history of climate related malaria epidemics. An improved understanding of malaria–climate interactions is needed to inform malaria control and national adaptation plans. Methods Malaria–climate associations in Ethiopia were assessed using (a) monthly climate data (1981–2016) from the Ethiopian National Meteorological Agency (NMA), (b) sea surface temperatures (SSTs) from the eastern Pacific, Indian Ocean and Tropical Atlantic and (c) historical malaria epidemic information obtained from the literature. Data analysed spanned 1950–2016. Individual analyses were undertaken over relevant time periods. The impact of the El Niño Southern Oscillation (ENSO) on seasonal and spatial patterns of rainfall and minimum temperature (Tmin) and maximum temperature (Tmax) was explored using NMA online Maprooms. The relationship of historic malaria epidemics (local or widespread) and concurrent ENSO phases (El Niño, Neutral, La Niña) and climate conditions (including drought) was explored in various ways. The relationships between SSTs (ENSO, Indian Ocean Dipole and Tropical Atlantic), rainfall, Tmin, Tmax and malaria epidemics in Amhara region were also explored. Results El Niño events are strongly related to higher Tmax across the country, drought in north-west Ethiopia during the July–August–September (JAS) rainy season and unusually heavy rain in the semi-arid south-east during the October–November–December (OND) season. La Niña conditions approximate the reverse. At the national level malaria epidemics mostly occur following the JAS rainy season and widespread epidemics are commonly associated with El Niño events when Tmax is high, and drought is common. In the Amhara region, malaria epidemics were not associated with ENSO, but with warm Tropical Atlantic SSTs and higher rainfall. Conclusion Malaria–climate relationships in Ethiopia are complex, unravelling them requires good climate and malaria data (as well as data on potential confounders) and an understanding of the regional and local climate system. The development of climate informed early warning systems must, therefore, target a specific region and season when predictability is high and where the climate drivers of malaria are sufficiently well understood. An El Niño event is likely in the coming years. Warming temperatures, political instability in some regions, and declining investments from international donors, implies an increasing risk of climate-related malaria epidemics

AG-9, an Elastin-Derived Peptide, Increases In Vitro Oral Tongue Carcinoma Cell Invasion, through an Increase in MMP-2 Secretion and MT1-MMP Expression, in a RPSA-Dependent Manner

Oral tongue squamous cell carcinoma is one of the most prevalent head and neck cancers. During tumor progression, elastin fragments are released in the tumor microenvironment. Among them, we previously identified a nonapeptide, AG-9, that stimulates melanoma progression in vivo in a mouse melanoma model. In the present paper, we studied AG-9 effect on tongue squamous cell carcinoma invasive properties. We demonstrated that AG-9 stimulates cell invasion in vitro in a modified Boyen chamber model. It increases MMP-2 secretion, analyzed by zymography and MT1-MMP expression, studied by Western blot. The stimulatory effect was mediated through Ribosomal Protein SA (RPSA) receptor binding as demonstrated by SiRNA experiments. The green tea-derived polyphenol, (−)-epigallocatechin-3-gallate (EGCG), was previously shown to bind RPSA. Molecular docking experiments were performed to compare the preferred areas of interaction of AG-9 and EGCG with RPSA and suggested overlapping areas. This was confirmed by competition assays. EGCG abolished AG-9-induced invasion, MMP-2 secretion, and MT1-MMP expression

Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review

Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed

λ-Carrageenan Oligosaccharides of Distinct Anti-Heparanase and Anticoagulant Activities Inhibit MDA-MB-231 Breast Cancer Cell Migration

In tumor development, the degradation of heparan sulfate (HS) by heparanase (HPSE) is associated with cell-surface and extracellular matrix remodeling as well as the release of HS-bound signaling molecules, allowing cancer cell migration, invasion and angiogenesis. Because of their structural similarity with HS, sulfated polysaccharides are considered a promising source of molecules to control these activities. In this study, we used a depolymerisation method for producing λ-carrageenan oligosaccharides (λ-CO), with progressive desulfation over time. These were then used to investigate the influence of polymeric chain length and degree of sulfation (DS) on their anti-HPSE activity. The effects of these two features on λ-CO anticoagulant properties were also investigated to eliminate a potential limitation on the use of a candidate λ-CO as a chemotherapeutic agent. HPSE inhibition was mainly related to the DS of λ-CO, however this correlation was not complete. On the other hand, both chain length and DS modulated λ-CO activity for factor Xa and thrombin IIa inhibition, two enzymes that are involved in the coagulation cascade, and different mechanisms of inhibition were observed. A λ-carrageenan oligosaccharide of 5.9 KDa was identified as a suitable anticancer candidate because it displayed one of the lowest anticoagulant properties among the λ-CO produced, while showing a remarkable inhibitory effect on MDA-MB-231 breast cancer cell migration