Theoretical Understanding of How Solution Properties Govern Nanofiltration Performances

Mechanisms governing transfer of ions through nanofiltration membranes are complex and it is primordial to understand how rejection and selectivity performances depend on the properties of the solution. For this purpose, a knowledge model based on a coupling between equilibrium partitioning induced by steric, electric and dielectric exclusions and transport inside pores by diffusion, convection and electro-migration is proposed to theoretically discuss the influence of solution properties on performances. After detailing the physical description of this model, the influence of ion size on rejection is firstly discussed from simulations obtained in several appropriate cases. Since electrostatic interactions are known to play a role on ion rejection, the influence of ion valence and concentration is then studied and different behaviors are brought to light depending on ions considered. Finally, the influence of confinement within nanopores on water dielectric properties and its consequences for ion separation are also addressed

Cytokine Profiles at Birth Predict Malaria Severity during Infancy

BACKGROUND: Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood. METHODS AND FINDINGS: Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10) were measured at birth (cord blood; N=783) and during subsequent routine follow-up visits (peripheral blood) for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman’s rank correlation). Cord levels of IL-1β and TNF-α (but not other cytokines) correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05). Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE) method), with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression): adjusted hazard ratio (95% CI) 0.60 (0.39-0.92), P = 0.02. CONCLUSION: IL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Etude comparative randomisée sur la génération de fer labile, dose dans l'ultrafiltrat, lors de l'administration intraveineuse de fer sucrose (Venofer®) et de fer dextran de bas poids moléculaire (Ferrisat®), chez les patients insuffisant rénaux chroniques en cours de séance d'hémodialyse

Le but de cette étude est de comparer la génération de fer labile, dosé dans l ultrafiltrat, lors de l administration de deux spécialités de fer intraveineux ; le fer sucrose (Venofer®) et le fer dextran de bas poids moléculaire (Ferrisat®), chez les patients insuffisants rénaux chroniques hémodialysés présentant une anémie par carence martiale et recevant de l érythropoïétine. Chez ces patients hémodialysés, les deux spécialités de fer intraveineux sont utilisées selon des protocoles d administration, pour corriger la carence martiale, tout en veillant à éviter les surcharges en fer, afin de limiter le stress oxydatif lié à la libération du fer labile bioactif lors de l administration du fer intraveineux.The objective of this study is to compare the generation of labile iron, dosed in the ultrafiltrate during the administration of two specialties of intravenous iron, the ironsucrose (Venofer ®) and iron dextran of low molecular weight (Ferrisat® ), in patients with chronic renal failure on hemodialysis with anemia and iron deficiency receiving erythropoietin. In these patients receiving hemodialysis, the two specialties are used as intravenous iron administration protocols to correct iron deficiency, while taking care to avoid iron overload, order to reduce oxidative stress associated with the release of iron labile bioactive during the administration of intravenous iron.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Transport à travers des membranes de nanofiltration (caractérisation des propriétés étectriques et diélectriques)

BESANCON-BU Sciences Staps (250562103) / SudocSudocFranceF

Etude du transport et de la rétention de solutés neutres et ioniques par le modèle DSPM : membranes de nano- et d'ultra-filtration fine

La modélisation du transport de matière à travers une structure microporeuse chargée constitue une étape indispensable à la compréhension de la sélectivité d'une membrane de nanofiltration. Dans ce travail, un modèle reposant sur l'équation étendue de Nernst-Planck pour décrire le transport et l'équation de Donnan modifiée pour décrire l'exclusion électrique-stérique des espèces est développé. Outre l'analyse théorique des phénomènes de transport, le modèle permet de relier les propriétés électriques et structurales d'une membrane au taux de rejet de solutés. Le rayon de pore (rp) et la charge volumique (X) de membranes ont pu être déduits de la modélisation des taux de rejets de solutés neutres et ioniques. La confrontation des valeurs de X et de rp à celles déduites de mesures indépendantes ne permet pas de conclure définitivement quant à la validité du modèle. Les résultats mettent en évidence un phénomène de régulation de charge intervenant à l'intérieur des pores de la membrane.Modeling of the matter transport through a charged microporous medium is a necessary step to understand and control the selectivity of a nanofiltration membrane. In this work, a model based on the application of the extended Nernst-Planck equation and the assumption of a modified Donnan equilibrium at both membrane/solution interfaces is developed. Besides the analysis of transport mechanisms, the model allows to relate a membrane's microscopic structural and charge properties to the solute retentions. The effective pore radius (rp) and effective volume charge (X) of nanofiltration membranes could be then determined by fitting the experimental retention of neutral and charged solutes. The comparison of the predicted values of the membrane X and rp with those determined from independent measurements does not allow to conclude definitively on the validity of the model. Results show that a charge regulation phenomenon occurs inside the membrane pores.BESANCON-BU Sciences Staps (250562103) / SudocSudocFranceF

Chapitre XIII. Traitement des eaux par nanofiltration : généralités, mécanismes et applications

1. Introduction À la base des processus vitaux, les membranes semi-perméables sont aujourd’hui utilisées dans de nombreux domaines et applications industrielles comme par exemple le dessalement de l’eau de mer et des eaux saumâtres, la concentration de jus de fruits, l’adoucissement d’eaux souterraines ou de surface, la déminéralisation des lactosérums, le traitement d’effluents des industries du papier, du bois et de la teinture, la clarification-désinfection des eaux potables, la concentrat..

Modelling the transport of asymmetric electrolytes through nanofiltration membranes

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