Histoire culturelle du monde byzantin, néo-hellénique et sud-est européen

Paolo Odorico, directeur d’études avec Roger David Scott, professeur à l’Université de MelbourneDimitris G. Apostolopoulos, directeur de recherche à l’Institut de recherches néo-helléniques du CNRS d’AthènesChristine Angelidi, directeur de recherche à l’Institut de recherches byzantines du CNRS d’Athènes Le but des séminaires était de présenter l’historiographie byzantine de deux époques différentes, qui peuvent être définies comme époques charnières : le VIe siècle, marqué par le passage de ..

Histoire culturelle du monde byzantin, néo-hellénique et sud-est européen

Paolo Odorico, directeur d’études avec Roger David Scott, professeur à l’Université de MelbourneDimitris G. Apostolopoulos, directeur de recherche à l’Institut de recherches néo-helléniques du CNRS d’AthènesChristine Angelidi, directeur de recherche à l’Institut de recherches byzantines du CNRS d’Athènes Le but des séminaires était de présenter l’historiographie byzantine de deux époques différentes, qui peuvent être définies comme époques charnières : le VIe siècle, marqué par le passage de ..

Gene Expression Profile of Neuronal Progenitor Cells Derived from hESCs: Activation of Chromosome 11p15.5 and Comparison to Human Dopaminergic Neurons

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined. PRINCIPAL FINDINGS: A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. CONCLUSIONS: The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons

Guidelines for the management of a brain death donor in the rhesus macaque: A translational transplant model.

The development of a translatable brain death animal model has significant potential to advance not only transplant research, but also the understanding of the pathophysiologic changes that occur in brain death and severe traumatic brain injury. The aim of this paper is to describe a rhesus macaque model of brain death designed to simulate the average time and medical management described in the human literature.Following approval by the Institutional Animal Care and Use Committee, a brain death model was developed. Non-human primates were monitored and maintained for 20 hours after brain death induction. Vasoactive agents and fluid boluses were administered to maintain hemodynamic stability. Endocrine derangements, particularly diabetes insipidus, were aggressively managed.A total of 9 rhesus macaque animals were included in the study. The expected hemodynamic instability of brain death in a rostral to caudal fashion was documented in terms of blood pressure and heart rate changes. During the maintenance phase of brain death, the animal's temperature and hemodynamics were maintained with goals of mean arterial pressure greater than 60mmHg and heart rate within 20 beats per minute of baseline. Resuscitation protocols are described so that future investigators may reproduce this model.We have developed a reproducible large animal primate model of brain death which simulates clinical scenarios and treatment. Our model offers the opportunity for researchers to have translational model to test the efficacy of therapeutic strategies prior to human clinical trials

In vitro characterization of genetically modified embryonic stem cells as a therapy for murine mucopolysaccharidosis type IIIA

The mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from the impaired catabolism of glycosaminoglycans (GAG). MPS type IIIA patients have dysfunctional sulfamidase enzyme leading to lysosomal storage of the GAG heparan sulfate, severe neurological symptoms including regression in learning, behavioural abnormalities, and premature death. We have engineered mouse D3 embryonic stem (ES) cells to over-express recombinant human sulfamidase. Human sulfamidase was correctly folded and secreted 2h post-labelling as determined by immunoprecipitation and SDS-PAGE analysis of transfected ES cells. Secreted human sulfamidase present in conditioned ES cell media was able to be taken up via mannose-6-phosphate-mediated endocytosis and restored sulfamidase enzyme activity in human MPS IIIA fibroblast cell lines. ES cells underwent directed differentiation to neural precursor populations and were capable of sustained human sulfamidase over-expression at all stages. Additionally, transfected and control cells were proliferative (Ki67+) and expressed several neural markers (nestin, MAP-2, and NF160) as determined by immunofluorescence. These findings suggest the possibility of ES cell-based therapy for the treatment of neurological pathology of MPS IIIA

Hemodynamics of brain death: Systolic blood pressure and heart rate.

<p>When examining the change is systolic blood pressure (SBP), there was a predicable hypertension, followed by hypotension before return to baseline. Fig 3B shows the individual SBP response to brain death and Fig 3A shows the average response for all animals. When change in HRs with BD there was a trend of slightly delayed tachycardia at 15 minutes after brain death, followed by slow return to a HR approximately 10–15 bpm above the animal’s original baseline by 1 hour post brain death. Fig 3C shows the individual HR response to brain death and Fig 3D shows the average response for all animals.</p

Kidney H&E analysis.

<p>Biopsy A shows Kidney H&E of naïve rhesus, age 18 years, diagnosed as normal. Biopsy B shows Kidney H&E of naïve rhesus, age 15 years, diagnosed with mild acute tubular injury, focal mild arteriosclerosis. Biospy C shows Kidney H&E of brain dead rhesus, age 16 years, diagnosed normal. Biopsy D shows Kidney H&E of naïve rhesus, age 19 years, diagnosed with mild acute tubular injury, focal mild arteriosclerosis.</p

Maintenance of brain death—Ventilation and oxygenation.

<p>Using by following serial ABGs and making appropriate ventilator adjustment, we were able to maintain adequate oxygenation and ventilation throughout brain death.</p