A congestion model for cell migration

This paper deals with a class of macroscopic models for cell migration in a saturated medium for two-species mixtures. Those species tend to achieve some motion according to a desired velocity, and congestion forces them to adapt their velocity. This adaptation is modelled by a correction velocity which is chosen minimal in a least-square sense. We are especially interested in two situations: a single active species moves in a passive matrix (cell migration) with a given desired velocity, and a closed-loop Keller-Segel type model, where the desired velocity is the gradient of a self-emitted chemoattractant. We propose a theoretical framework for the open-loop model (desired velocities are defined as gradients of given functions) based on a formulation in the form of a gradient flow in the Wasserstein space. We propose a numerical strategy to discretize the model, and illustrate its behaviour in the case of a prescribed velocity, and for the saturated Keller-Segel model

DEPRESSION, FAMILY AND CELLULAR IMMUNITY: INFLUENCE OF FAMILY RELATIONSHIPS AND CELLULAR IMMUNITY ON THE SEVERITY OF DEPRESSION

Background: Exposure to stress activates the hypothalamic-pituitary-adrenal axis through the release of catecholamines, which modify humoral and cellular immunity. On the one hand, this psycho-immunological theory makes it possible to forge links between immunity and depression. On the other hand, we know that family determinants are an important variable in the model of vulnerability to depression. Our study weighs the influence of cellular immunity and family relations on the severity of depression. Subjects and method: 498 inpatients with major depressive disorder were enrolled in an open-label trial. In addition to a sociodemographic questionnaire, they completed Olsen’s FACES III and the Beck Depression Inventory (BDI). Flow cytometry was used to assess lymphocyte subsets. Results: In terms of immunity, there are correlations between the BDI and percentages of CD3 (p=0.015; r=-0.112), CD4 (p<0.000; r=-0.175), CD4/CD8 (p=0.045; r=-0.093) and CD16 and 56 (p=0.014; r=0.113). In terms of family relationships, there is a correlation between the BDI and family of origin, both for cohesion (p=0.007; r=-0.169) and adaptability (p=0.035; r=-0.133) measures. With respect to the relationship between family dynamics and immunity, there are correlations between adaptability in the family of origin and CD3 (p=0.04; r=0.094) and CD4 (p=0.044; r=0.093). A logistic regression model for family variables explained 11.4% of the BDI, compared to 12.7% for immune variables, while a model including the two explained 16%. Conclusions: While both the family and immunity can explain the BDI, it is surprising they have a greater effect in combination than individually. This suggests that the psycho-immunological theory should look at the relation between immunity and family life, notably in relation to the family of origin

FUNCTIONAL MODULATION OF HUMAN PLURIPOTENT STEM CELLS BY O-LINKED N-ACETYLGUCOSAMINE

Ph.DDOCTOR OF PHILOSOPH

Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Treatment of <i>N</i>′-aryl urea derivatives of enantiomerically enriched α-(2-pyridyl) and α-(3-pyridyl)­alkylamines with a base leads to the migration of the <i>N</i>′-aryl substituent from N to C in a ‘nonclassical’ intramolecular nucleophilic aromatic substitution reaction. Both electron-rich and -poor rings migrate successfully. A new quaternary stereogenic center is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines

Conception, realization and characterization of a very high negative chromatic dispersion fiber

International audienceAfter a brief presentation ..

Identification of pyridine analogs as new predator-derived kairomones.

In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a "from the wild to the lab" approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication

A worldwide survey on incidence, management and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: The POTTER-AF study.

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management and outcome are sparse. METHODS AND RESULTS This international multicenter registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553,729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed at 214 centers in 35 countries. In 78 centers 138 patients (0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (p<0.0001)) were diagnosed with an oesophageal fistula. Periprocedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8%, and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) (odds ratio 7.463 (2.414, 23.072) p<0.001). CONCLUSIONS Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

O -GlcNAc and Neurodegeneration: Biochemical Mechanisms and Potential Roles in Alzheimer\u27s Disease and Beyond

Alzheimer disease (AD) is a growing problem for aging populations worldwide. Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies. Longitudinal studies have clarified that defects in glucose metabolism occur in patients exhibiting Mild Cognitive Impairment (MCI) and glucose hypometabolism is an early pathological change within AD brain. Further, type 2 diabetes mellitus (T2DM) is a strong risk factor for the development of AD. These findings have stimulated interest in the possibility that disrupted glucose regulated signaling within the brain could contribute to the progression of AD. One such process of interest is the addition of O-linked N-acetylglucosamine (O-GlcNAc) residues onto nuclear and cytoplasmic proteins within mammals. O-GlcNAc is notably abundant within brain and is present on hundreds of proteins including several, such as tau and the amyloid precursor protein, which are involved in the pathophysiology AD. The cellular levels of O-GlcNAc are coupled to nutrient availability through the action of just two enzymes. O-GlcNAc transferase (OGT) is the glycosyltransferase that acts to install O-GlcNAc onto proteins and O-GlcNAcase (OGA) is the glycoside hydrolase that acts to remove O-GlcNAc from proteins. Uridine 5′-diphosphate-N-acetylglucosamine (UDP-GlcNAc) is the donor sugar substrate for OGT and its levels vary with cellular glucose availability because it is generated from glucose through the hexosamine biosynthetic pathway (HBSP). Within the brains of AD patients O-GlcNAc levels have been found to be decreased and aggregates of tau appear to lack O-GlcNAc entirely. Accordingly, glucose hypometabolism within the brain may result in disruption of the normal functions of O-GlcNAc within the brain and thereby contribute to downstream neurodegeneration. While this hypothesis remains largely speculative, recent studies using different mouse models of AD have demonstrated the protective benefit of pharmacologically increased brain O-GlcNAc levels. In this review we summarize the state of knowledge in the area of O-GlcNAc as it pertains to AD while also addressing some of the basic biochemical roles of O-GlcNAc and how these might contribute to protecting against AD and other neurodegenerative diseases

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings