Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs.

BACKGROUND: Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions. OBJECTIVES: To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene. METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes. RESULTS: Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs. CONCLUSIONS: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.

Jumping Jack Flash.

A 38-year-old woman presented with blurred vision and "jumping" of the right eye for 7 months. Magnetic resonance imaging of the head was normal. Intermittent intorsion of the right eye was noted on examination, consistent with superior oblique myokymia. She was initially treated with carbamazepine but stopped after becoming light-headed. The diagnosis and treatment of superior oblique myokymia are discussed.

Hybridisation and diversification in the adaptive radiation of clownfishes.

BackgroundThe importance of hybridisation during species diversification has long been debated among evolutionary biologists. It is increasingly recognised that hybridisation events occurred during the evolutionary history of numerous species, especially during the early stages of adaptive radiation. We study the effect of hybridisation on diversification in the clownfishes, a clade of coral reef fish that diversified through an adaptive radiation process. While two species of clownfish are likely to have been described from hybrid specimens, the occurrence and effect of hybridisation on the clade diversification is yet unknown.ResultsWe generate sequences of three mitochondrial genes to complete an existing dataset of nuclear sequences and document cytonuclear discordance at a node, which shows a drastic increase of diversification rate. Then, using a tree-based jack-knife method, we identify clownfish species likely stemming from hybridisation events. Finally, we use molecular cloning and identify the putative parental species of four clownfish specimens that display the morphological characteristics of hybrids.ConclusionsOur results show that consistently with the syngameon hypothesis, hybridisation events are linked with a burst of diversification in the clownfishes. Moreover, several recently diverged clownfish lineages likely originated through hybridisation, which indicates that diversification, catalysed by hybridisation events, may still be happening.

Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.

Regulatory assessment of in vitro skin corrosion and irritation data within the European framework: Workshop recommendations

Validated in vitro methods for skin corrosion and irritation were adopted by the OECD and by the European Union during the last decade. In the EU, Switzerland and countries adopting the EU legislation, these assays may allow the full replacement of animal testing for identifying and classifying compounds as skin corrosives, skin irritants, and non irritants. In order to develop harmonised recommendations on the use of in vitro data for regulatory assessment purposes within the European framework, a workshop was organized by the Swiss Federal Office of Public Health together with ECVAM and the BfR. It comprised stakeholders from various European countries involved in the process from in vitro testing to the regulatory assessment of in vitro data. Discussions addressed the following questions: (1) the information requirements considered useful for regulatory assessment; (2) the applicability of in vitro skin corrosion data to assign the corrosive subcategories as implemented by the EU Classification, Labelling and Packaging Regulation; (3) the applicability of testing strategies for determining skin corrosion and irritation hazards; and (4) the applicability of the adopted in vitro assays to test mixtures, preparations and dilutions. Overall, a number of agreements and recommendations were achieved in order to clarify and facilitate the assessment and use of in vitro data from regulatory accepted methods, and ultimately help regulators and scientists facing with the new in vitro approaches to evaluate skin irritation and corrosion hazards and risks without animal data.

Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Automatic classification of MR scans in Alzheimer's disease.

To be diagnostically useful, structural MRI must reliably distinguish Alzheimer's disease (AD) from normal aging in individual scans. Recent advances in statistical learning theory have led to the application of support vector machines to MRI for detection of a variety of disease states. The aims of this study were to assess how successfully support vector machines assigned individual diagnoses and to determine whether data-sets combined from multiple scanners and different centres could be used to obtain effective classification of scans. We used linear support vector machines to classify the grey matter segment of T1-weighted MR scans from pathologically proven AD patients and cognitively normal elderly individuals obtained from two centres with different scanning equipment. Because the clinical diagnosis of mild AD is difficult we also tested the ability of support vector machines to differentiate control scans from patients without post-mortem confirmation. Finally we sought to use these methods to differentiate scans between patients suffering from AD from those with frontotemporal lobar degeneration. Up to 96% of pathologically verified AD patients were correctly classified using whole brain images. Data from different centres were successfully combined achieving comparable results from the separate analyses. Importantly, data from one centre could be used to train a support vector machine to accurately differentiate AD and normal ageing scans obtained from another centre with different subjects and different scanner equipment. Patients with mild, clinically probable AD and age/sex matched controls were correctly separated in 89% of cases which is compatible with published diagnosis rates in the best clinical centres. This method correctly assigned 89% of patients with post-mortem confirmed diagnosis of either AD or frontotemporal lobar degeneration to their respective group. Our study leads to three conclusions: Firstly, support vector machines successfully separate patients with AD from healthy aging subjects. Secondly, they perform well in the differential diagnosis of two different forms of dementia. Thirdly, the method is robust and can be generalized across different centres. This suggests an important role for computer based diagnostic image analysis for clinical practice.

Automatic quality assessment in structural brain magnetic resonance imaging

MRI has evolved into an important diagnostic technique in medical imaging. However, reliability of the derived diagnosis can be degraded by artifacts, which challenge both radiologists and automatic computer-aided diagnosis. This work proposes a fully-automatic method for measuring image quality of three-dimensional (3D) structural MRI. Quality measures are derived by analyzing the air background of magnitude images and are capable of detecting image degradation from several sources, including bulk motion, residual magnetization from incomplete spoiling, blurring, and ghosting. The method has been validated on 749 3D T(1)-weighted 1.5T and 3T head scans acquired at 36 Alzheimer's Disease Neuroimaging Initiative (ADNI) study sites operating with various software and hardware combinations. Results are compared against qualitative grades assigned by the ADNI quality control center (taken as the reference standard). The derived quality indices are independent of the MRI system used and agree with the reference standard quality ratings with high sensitivity and specificity (>85%). The proposed procedures for quality assessment could be of great value for both research and routine clinical imaging. It could greatly improve workflow through its ability to rule out the need for a repeat scan while the patient is still in the magnet bore.

Présentation du dossier

Présentation du dossier Spinoza politique - Penser la puissance de la multitude Présentation effectuée à titre d'éditeur scientifique du dossier comprenant les articles suivants: - Laurent Bove, A quoi est tenu le corps d'une multitude afin d'échapper à la domination? La leçon de Spinoza dans le Traité politique - Charles Ramond, Le Traité politique de Spinoza - vers une démocratie sans valeurs? - Chantal Jaquet, L'accord affectif de la multitude. Le désir (desiderium) de vengeance comme principe du corps politique - Hugues Poltier, Multitude libre/Multitude serve. Pour une lecture du Traité politique de Spinoza - Jack Stetter, L'Etat comme âme, le citoyen comme soumis et comme résistant