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يأتي هذا الأطلس الذي يمثل أداة عمل أساسية قام بإعداده اثنان من رسامي الخرائط وعالمة جغرافيا وخبيران في العلوم السياسية وهو ثمرة عمل جماعي حول موضوع الفضاء العالمي المعاصر الذي يعتبر واحدا من الدروس الرائدة في معهد العلوم السياسية وقد أفرد مساحة واسعة لهذه المسائل يندرج في إطار التجدد العميق للتحليلات الدولية ويعبر بدقة عما يميز المقاربة الفرنسية للعلاقات الدولية وإن هذه المقاربة التي هي اجتماعية أكثر مما كونها سياسية بالشكل المباشر والمنفتحة على تعدد الفاعلين وعلى أكثر العنف الاجتماعي والنزاعات والمفضلة لكافة أشكال التضامن والتكامل على حساب الصراع الكلاسيكي والسلطة السياسية التي ليست في أحسن أحوالها وهذه المقاربة تجد نفسها بعمق في إطار نظرة للفضاء تتمايز عن الجغرافيا السياسية التقليدية وكذلك عن المطابقة لمفهوم الأرض الكلاسيكي ومن الواضح أن هذا الإطار الجديد يفرض تحولا فكريا وعلميا وتربويا ولذا لابد من بذل جهد لتخطي العلاقات الدولية القديمة وبالتالي لا يتوقف عند العلاقات بين الدول والأمم فقط بل تبرز دور المجتمعات والفاعلين الاجتماعيين والقضايا المجتمعية والأفراد الذين يشاركون بقوة.

Staphylococcus aureus is an important opportunistic pathogen of humans and animals. it produces extracellular vesicles (EVs) that are involved in cellular communication and enable inter-kingdom crosstalk, the delivery of virulence factors and modulation of the host immune response. The protein content of EVs determines their biological functions. Clarifying which proteins are selected, and how, is of crucial value to understanding the role of EVs in pathogenesis and the development of molecular delivery systems. Here, we postulated that S. aureus EVs share a common proteome containing components involved in cargo sorting. The EV proteomes of five S. aureus strains originating from human, bovine, and ovine hosts were characterised. The clustering of EV proteomes reflected the diversity of the producing strains. A total of 253 proteins were identified, 119 of which composed a core EV proteome with functions in bacterial survival, pathogenesis, and putatively in EV biology. We also identified features in the sequences of EV proteins and the corresponding genes that could account for their packaging into EVs. Our findings corroborate the hypothesis of a selective sorting of proteins into EVs and offer new perspectives concerning the roles of EVs in S. aureus pathogenesis in specific host niches. Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes a broad spectrum of infections in humans and animals. In humans, these diseases range from superficial skin and soft tissue infections to life-threatening conditions that require hospitalisation and extensive medical support 1,2. This bacterium is also one of the main causative agents of nosocomial infections. In animals, S. aureus is notably responsible for ruminant mastitis, an inflammation of the mammary glands that dramatically affects animal health and welfare, milk quality and the economics of milk production 3. Mastitis is also the principal reason for the use of antibiotics in dairy herds 4. The wide range of clinical manifestations of S. aureus infections is likely associated with its huge arsenal of virulence factors, which include structural components and extracellular factors such as enzymes and toxins 5. Despite considerable efforts, the precise mechanisms underlying host adaptation, colonisation and interactions are not yet fully understood 6. Extracellular vesicles (EVs) are used by many pathogenic bacteria as a secretory route to deliver toxic compounds to infected cells 7,8. EVs are lipid bilayer nanoparticles that range in size from 20 to 300 nm and are released by almost all cells in all domains of life 9. In Gram-positive bacteria, they are formed by budding and shedding of the cytoplasmic membrane. They play a pivotal role in cell-to-cell communication through their ability to transport bioactive molecules (proteins, nucleic acids, lipids, metabolites) from donor to recipient cells. The EVs produced by S. aureus can mediate the pathogenesis of infection in a variety of ways. They may be cytotoxic to host cells 10-12 , induce the production of cytokines 13-18 , contribute to biofilm formation 19 , mediate antibiotic

AbstractBackgroundGenome-wide association studies (GWAS) were performed at the sequence level to identify candidate mutations that affect the expression of six major milk proteins in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) dairy cattle. Whey protein (α-lactalbumin and β-lactoglobulin) and casein (αs1, αs2, β, and κ) contents were estimated by mid-infrared (MIR) spectrometry, with medium to high accuracy (0.59 ≤ R2 ≤ 0.92), for 848,068 test-day milk samples from 156,660 cows in the first three lactations. Milk composition was evaluated as average test-day measurements adjusted for environmental effects. Next, we genotyped a subset of 8080 cows (2967 MON, 2737 NOR, and 2306 HOL) with the BovineSNP50 Beadchip. For each breed, genotypes were first imputed to high-density (HD) using HD single nucleotide polymorphisms (SNPs) genotypes of 522 MON, 546 NOR, and 776 HOL bulls. The resulting HD SNP genotypes were subsequently imputed to the sequence level using 27 million high-quality sequence variants selected from Run4 of the 1000 Bull Genomes consortium (1147 bulls). Within-breed, multi-breed, and conditional GWAS were performed.ResultsThirty-four distinct genomic regions were identified. Three regions on chromosomes 6, 11, and 20 had very significant effects on milk composition and were shared across the three breeds. Other significant effects, which partially overlapped across breeds, were found on almost all the autosomes. Multi-breed analyses provided a larger number of significant genomic regions with smaller confidence intervals than within-breed analyses. Combinations of within-breed, multi-breed, and conditional analyses led to the identification of putative causative variants in several candidate genes that presented significant protein–protein interactions enrichment, including those with previously described effects on milk composition (SLC37A1, MGST1, ABCG2, CSN1S1, CSN2, CSN1S2, CSN3, PAEP, DGAT1, AGPAT6) and those with effects reported for the first time here (ALPL, ANKH, PICALM).ConclusionsGWAS applied to fine-scale phenotypes, multiple breeds, and whole-genome sequences seems to be effective to identify candidate gene variants. However, although we identified functional links between some candidate genes and milk phenotypes, the causality between candidate variants and milk protein composition remains to be demonstrated. Nevertheless, the identification of potential causative mutations that underlie milk protein composition may have immediate applications for improvements in cheese-making.

Extracellular vesicles (EVs) are biological vectors that can modulate the metabolism of target cells by conveying signalling proteins and genomic material. The level of EVs in plasma is significantly increased in cardiometabolic diseases associated with obesity, suggesting their possible participation in the development of metabolic dysfunction. With regard to the poor definition of adipocyte-derived EVs, the purpose of this study was to characterise both qualitatively and quantitatively EVs subpopulations secreted by fat cells. Adipocyte-derived EVs were isolated by differential centrifugation of conditioned media collected from 3T3-L1 adipocytes cultured for 24 h in serum-free conditions. Based on morphological and biochemical properties, as well as quantification of secreted EVs, we distinguished two subpopulations of adipocyte-derived EVs, namely small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs). Proteomic analyses revealed that lEVs and sEVs exhibit specific protein signatures, allowing us not only to define novel markers of each population, but also to predict their biological functions. Despite similar phospholipid patterns, the comparative lipidomic analysis performed on these EV subclasses revealed a specific cholesterol enrichment of the sEV population, whereas lEVs were characterised by high amounts of externalised phosphatidylserine. Enhanced secretion of lEVs and sEVs is achievable following exposure to different biological stimuli related to the chronic low-grade inflammation state associated with obesity. Finally, we demonstrate the ability of primary murine adipocytes to secrete sEVs and lEVs, which display physical and biological characteristics similar to those described for 3T3-L1. Our study provides additional information and elements to define EV subtypes based on the characterisation of adipocyte-derived EV populations. It also underscores the need to distinguish EV subpopulations, through a combination of multiple approaches and markers, since their specific composition may cause distinct metabolic responses in recipient cells and tissues.

Nutritional suitability of milk is not only related to gross composition, but is also strongly affected by the microheterogeniety of the protein fraction. Hence, to go further into the evaluation of the potential suitability of non-bovine milks in human/infant nutrition it is necessary to have a detailed characterization of their protein components. Combining proven proteomic approaches (SDS-PAGE, LC-MS/MS and LC-ESI-MS) and cDNA sequencing, we provide here in depth characterization of the milk protein fraction of dromedary and Bactrian camels, and their hybrids, from different regions of Kazakhstan. A total 391 functional groups of proteins were identified from 8 camel milk samples. A detailed characterization of 50 protein molecules, relating to genetic variants and isoforms arising from post-translational modifications and alternative splicing events, belonging to nine protein families (κ-, αs1-, αs2-, β-; and γ-CN, WAP, α-LAC, PGRP, CSA/LPO) was achieved by LC-ESI-MS. The presence of two unknown proteins UP1 (22,939 Da) and UP2 (23,046 Da) was also reported as well as the existence of a β-CN short isoform (946 Da lighter than the full-length β-CN), arising very likely in both genetic variants (A and B) from proteolysis by plasmin. In addition, we report, for the first time to our knowledge, the occurrence of a αs2-CN phosphorylation isoform with 12P groups within two recognition motifs, suggesting thereby the existence of two kinase systems involved in the phosphorylation of caseins in the mammary gland. Finally, we demonstrate that genetic variants, which hitherto seemed to be species- specific (e.g. β-CN A for Bactrian and β-CN B for dromedary), are in fact present both in Camel dromedarius and C. bactrianus.

Abstract miRNAs present in milk are mainly found in extracellular vesicles (EVs), which are nanosized membrane vesicles released by most of the cell types to ensure intercellular communication. The majority of the studies performed so far on these vesicles have been conducted on human and cow’s milk and focused on their miRNA content. The objectives of this study were to profile the miRNA content of purified EVs from five healthy goats and to compare their miRNome to those obtained from five healthy cows, at an early stage of lactation. EV populations were morphologically characterized using Transmission Electron Microscopy and Nanoparticle Tracking Analysis. The presence of EV protein markers checked by Western blotting and the absence of contamination of preparations by milk proteins. The size distribution and concentration of bovine and goat milk-derived EVs were similar. RNA-sequencing were performed, and all sequences were mapped to the cow genome identifying a total of 295 miRNAs. This study reports for the first-time a goat miRNome from milk EVs and its validation using cow miRNomes.

In a previous study on camel milk from Kazakhstan, we reported the occurrence of two unknown proteins (UP1 and UP2) with different levels of phosphorylation. Here we show that UP1 and UP2 are isoforms of camel αs2-CN (αs2-CNsv1 and αs2-CNsv2, respectively) arising from alternative splicing events. First described as a 178 amino-acids long protein carrying eight phosphate groups, the major camel αs2-CN isoform (called here αs2-CN) has a molecular mass of 21,906 Da. αs2-CNsv1, a rather frequent (35%) isoform displaying a higher molecular mass (+1,033 Da), is present at four phosphorylation levels (8P to 11P). Using cDNA-sequencing, αs2-CNsv1 was shown to be a variant arising from the splicing-in of an in-frame 27-nucleotide sequence encoding the nonapeptide ENSKKTVDM, for which the presence at the genome level was confirmed. αs2-CNsv2, which appeared to be present at 8P to 12P, was shown to include an additional decapeptide (VKAYQIIPNL) revealed by LC-MS/MS, encoded by a 3'-extension of exon 16. Since milk proteins represent a reservoir of biologically active peptides, the molecular diversity generated by differential splicing might increase its content. To evaluate this possibility, we searched for bioactive peptides encrypted in the different camel αs2-CN isoforms, using an in silico approach. Several peptides, putatively released from the C-terminal part of camel αs2-CN isoforms after in silico digestion by proteases from the digestive tract, were predicted to display anti-bacterial and antihypertensive activities.

Background Successful achievement of early folliculogenesis is crucial for female reproductive function. The process is finely regulated by cell-cell interactions and by the coordinated expression of genes in both the oocyte and in granulosa cells. Despite many studies, little is known about the cell-specific gene expression driving early folliculogenesis. The very small size of these follicles and the mixture of types of follicles within the developing ovary make the experimental study of isolated follicular components very difficult. The recently developed laser capture microdissection (LCM) technique coupled with microarray experiments is a promising way to address the molecular profile of pure cell populations. However, one main challenge was to preserve the RNA quality during the isolation of single cells or groups of cells and also to obtain sufficient amounts of RNA. Using a new LCM method, we describe here the separate expression profiles of oocytes and follicular cells during the first stages of sheep folliculogenesis. Results We developed a new tissue fixation protocol ensuring efficient single cell capture and RNA integrity during the microdissection procedure. Enrichment in specific cell types was controlled by qRT-PCR analysis of known genes: six oocyte-specific genes ( SOHLH2 , MAEL , MATER , VASA , GDF9 , BMP15 ) and three granulosa cell-specific genes ( KL , GATA4 , AMH ). A global gene expression profile for each follicular compartment during early developmental stages was identified here for the first time, using a bovine Affymetrix chip. Most notably, the granulosa cell dataset is unique to date. The comparison of oocyte vs. follicular cell transcriptomes revealed 1050 transcripts specific to the granulosa cell and 759 specific to the oocyte. Functional analyses allowed the characterization of the three main cellular events involved in early folliculogenesis and confirmed the relevance and potential of LCM-derived RNA. Conclusions The ovary is a complex mixture of different cell types. Distinct cell populations need therefore to be analyzed for a better understanding of their potential interactions. LCM and microarray analysis allowed us to identify novel gene expression patterns in follicular cells at different stages and in oocyte populations.

In this work, impedimetric sensors were developed for the detection of the four WFD heavy metals Pb2+, Cd2+, Hg2+ and Ni2+, by the modification of a gold electrode with four partially biosourced polyphosphine polymers. These polymers were obtained with satisfactory yields by polycondensation of the bis(4-fluorophenyl)(4-methylphenyl)phosphine sulfide and the bis(4-fluorophenyl)(4-methylphenyl)phosphine oxide using isosorbide or bisphenol A. The chemical structures and number-average molecular weights of the resulting polymers were determined by NMR spectroscopy (1H, 19F, and 31P) and by size exclusion chromatography. Glass transition temperatures varied between 184 and 202 °C depending on the composition of polymers. The bio-based poly(etherphosphine) oxide modified sensor showed better analytical performance than petrochemical based oxide for the detection of Pb2+. A detection limit of 10−10 g/L or 0.5 pM, which is 104 times lower than that of the anodic stripping voltammetric and the potentiometric sensors. A reversibility is obtained through rinsing of the impedimetric sensor with an EDTA solution.