Longitudinal stability of the folding pattern of the anterior cingulate cortex during development.

Prenatal processes are likely critical for the differences in cognitive ability and disease risk that unfold in postnatal life. Prenatally established cortical folding patterns are increasingly studied as an adult proxy for earlier development events - under the as yet untested assumption that an individual's folding pattern is developmentally fixed. Here, we provide the first empirical test of this stability assumption using 263 longitudinally-acquired structural MRI brain scans from 75 typically developing individuals spanning ages 7 to 32 years. We focus on the anterior cingulate cortex (ACC) - an intensely studied cortical region that presents two qualitatively distinct and reliably classifiable sulcal patterns with links to postnatal behavior. We show - without exception-that individual ACC sulcal patterns are fixed from childhood to adulthood, at the same time that quantitative anatomical ACC metrics are undergoing profound developmental change. Our findings buttress use of folding typology as a postnatally-stable marker for linking variations in early brain development to later neurocognitive outcomes in ex utero life.

Statement of severe trauma management in France; teachings of the FIRST study.

INTRODUCTION: The blunt trauma victim management is still a matter of debate and comparing studies involving different emergency medical services and health care organization remains fictitious. Hence, the French Intensive care Recorded in Severe Trauma (FIRST) was conducted in order to describe the severe blunt trauma management in France. The present paper aimed at recalling the main results of FIRST study. METHODS: The FIRST study was based on a multicenter prospective cohort of patients aged 18 or over with severe exclusive blunt trauma requiring admission to university hospital care unit within the first 72h and/or managed by medical-Staffed Emergency Mobile Unit (SMUR). Multiple data were collected about patient characteristics, clinical initial status, typology of trauma and the main endpoints were 30-day mortality. RESULTS: Sixty-one percent of trauma patients were road traffic victims and 30% were domestic, sport or leisure trauma. Patients who benefited from medical pre-hospital management were globally more severely injured than those who received basic life support care by fire brigades. Therefore, they were delivered more aggressive treatment in the pre-hospital setting and the median time for their hospital admission was lengthened. However, their 30-day mortality was significantly reduced. The probability of death was also decreased when casualties were transported by SMUR helicopter directly to the university hospital. In the in-hospital setting, the performance of a whole-body computed tomography (CT) was associated with a significant reduction in the mortality risk compared with a selective CT. CONCLUSION: The FIRST study suggests the benefit of a medical management in the pre-hospital setting on the survival of trauma patients. The emergency physician (EP) expertise in the pre-hospital and initial hospital phases would lead to the concept of the appropriate care for the appropriate trauma patient. It also highlights the necessity to set up organized regional sectors of care and registries.

[Development of cardiac physiopathological models from cultured cardiomyocytes]. / Développement de modèles physiopathologiques cardiaques a partir des cultures de cardiomyocytes.

The cultures of neonatal rat cardiomyocytes represent a very useful tool for the observation and the understanding of the cellular aspects of the electrophysiological, contractile, morphological, metabolic and molecular properties of the myocardium. This model is characterized by a homogeneous population of cardiac muscular cells and by vast possibilities of control of the chemical and physical environment of the cells, allowing the in vitro mimicry of a wide range of cardiac pathological situations. The cardiomyocyte cultures are thus suited to very varied experimental protocols, allowing multiparametric analysis of the cardiocellular effects of different stress such as hypoxia-reoxygenation, of ischemia-reperfusion, of the free radical attack and of thermal shock. These investigations can be combined with the study of the effects and of the cytotoxicity of pharmacological agents, not limited to the putatively cardioactive drugs. The present review proposes an outline of the procedures for the isolation, the culture and the use of neonatal cardiomyocytes. To illustrate the potentialities of this preparation, we describe more specifically the protocols and the various consequences at the cellular scale of an in vitro model of myocardial ischemia reperfusion.

Influence of deep hypothermia on the tolerance of the isolated cardiomyocyte to ischemia-reperfusion.

The influence of deep hypothermia (4 degrees C) during a substrate-free, hypoxia-reoxygenation treatment was investigated on cardiomyocytes (CM) prepared from newborn rat heart in culture in an in vitro, substrate-free model of ischemia-reperfusion. The transmembranous potentials were recorded with standard microelectrodes. The contractions were monitored photometrically. The RNA messenger (mRNA) and protein expression for protein (HSP70) were analysed by RT-PCR (reverse transcriptase-polymerase chain reaction) and Western blotting, respectively. Simulated ischemia (SI) caused a gradual decrease and then a cessation of the spontaneous electromechanical activity. During the reoxygenation, the CM recovered normal function, provided that SI did not exceed 2.5 h. When SI duration was increased up to 4 h, reoxygenation failed to restore the spontaneous electromechanical activity. Conversely, the exposure of the CM to SI together with deep hypothermia decreased the functional alterations observed, and provided a complete electromechanical recovery after 2.5 h as well as after 4 h of SI. Deep hypothermia alone failed to induce HSP70 mRNA and protein production. On the contrary, HSP70 mRNA production increased after 2.5 and 4 h of deep hypothermia followed by 1 h of rewarming, proportionally to the duration of the cooling period. This augmentation in mRNA was associated with a rise in HSP70 protein content. In summary, it appeared that deep hypothermia exerts a strong cytoprotective action during SI only, whereas cooling CM before SI has no beneficial effect on subsequent SI. Moreover, these results suggested the persistence of a signaling system and/or transduction in deeply cooled, functionally depressed cells. Finally, CM in culture appeared to be a model of interest for studying heart graft protection against ischemia-reperfusion and contributed to clarifying the molecular and cellular mechanisms of deep hypothermia on myocardium.

Distinct Albino3-dependent and -independent pathways for thylakoid membrane protein insertion.

The homologous proteins Oxa1, YidC, and Alb3 mediate the insertion of membrane proteins in mitochondria, bacteria, and chloroplast thylakoids, respectively. Depletion of YidC in Escherichia coli affects the integration of every membrane protein studied, and Alb3 has been shown previously to be required for the insertion of a signal recognition particle (SRP)-dependent protein, Lhcb1, in thylakoids. In this study we have analyzed the "global" role of Alb3 in the insertion of thylakoid membrane proteins. We show that insertion of two chlorophyll-binding proteins, Lhcb4.1 and Lhcb5, is almost totally blocked by preincubation of thylakoids with anti-Alb3 antibodies, indicating a requirement for Alb3 in the insertion pathway. Insertion of the related PsbS protein, on the other hand, is unaffected by Alb3 antibodies, and insertion of a group of SRP-independent, signal peptide-bearing proteins, PsbX, PsbW, and PsbY, is likewise completely unaffected. Proteinase K is furthermore able to completely degrade Alb3, but this treatment does not affect the insertion of these proteins. Among the thylakoid proteins studied here, Alb3 requirement correlates strictly with a requirement for stromal factors and nucleoside triphosphates. However, the majority of proteins tested do not require Alb3 or any other known form of translocation apparatus.

The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis.

Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf phenotypes in plants. Understanding the regulation of BR biosynthesis demands continued isolation and characterization of mutants corresponding to the genes involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results from feeding studies with 13C-labeled mevalonic acid and compactin show that the defective step is specifically the Delta7 sterol C-5 desaturation, suggesting that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7.