Micro-MRI Study of Cerebral Aging: Ex Vivo Detection of Hippocampal Subfield Reorganization,Microhemorrhages and Amyloid Plaques in Mouse Lemur Primates

Mouse lemurs are non-human primate models of cerebral aging and neurodegeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 µm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon''s horn. We show that both dentate gyrus and Ammon''s horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon''s horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral microhemorrhages.     

FiRe and microarrays: a fast answer to burning questions

FiRe is a user-friendly Excel macro designed to survey microarray data rapidly. This software interactively assembles data from different experiments and produces lists of candidate genes according to patterns of gene expression. Furthermore, macros bundled with FiRe can compare lists of genes, merge information from different spreadsheets, link candidates to information available from web-based databases, and produce heat-maps for easy visualization of microarray data. FiRe is freely available at http://www.unifr.ch/plantbio/FiRe/main.html .     

Epidemiology of Alzheimer disease and related disorders

Alzheimer's disease and related disorders (dementia) are a major public health problem due to the number of cases in the general population, the projections for the future, and the consequences of these diseases. We can estimate that about 850 000 cases of dementia were present in France in 2005 and this number will increase to 1,200,000 in 2020 and 2,100,000 in 2040 if the incidence and the duration of the disease did not change. The development of prevention is therefore necessary. Four ways of prevention are credible. The most important is the treatment of vascular risk factors and particularly hypertension. Other ways are nutritional factors, stimulating leisure activities and depression.     

Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy

Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1(p44), and VP1(p108). Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1(p44)) and 5 of 10 (VP1(p108)) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1(p44) were more abundant than against VP1(p108) in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1(p36) and VP1(p100). A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses.     

GenMiner: mining non-redundant association rules from integrated gene expression data and annotations

GenMiner is an implementation of association rule discovery dedicated to the analysis of genomic data. It allows the analysis of datasets integrating multiple sources of biological data represented as both discrete values, such as gene annotations, and continuous values, such as gene expression measures. GenMiner implements the new NorDi (normal discretization) algorithm for normalizing and discretizing continuous values and takes advantage of the Close algorithm to efficiently generate minimal non-redundant association rules. Experiments show that execution time and memory usage of GenMiner are significantly smaller than those of the standard Apriori-based approach, as well as the number of extracted association rules. AVAILABILITY: The GenMiner software and supplementary materials are available at http://bioinfo.unice.fr/publications/genminer_article/ and http://keia.i3s.unice.fr/?Implementations:GenMiner SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Differential expression of creatine kinase isozymes during development of Xenopus laevis: An unusual heterodimeric isozyme appears at metamorphosis

The creatine kinase (CK) repertoire of Xenopus laevis, which is more complex than that of most other vertebrates, involves at least four genomic loci, all showing developmental and tissue-specific expression. The differential expression of this multilocus CK isozyme system was investigated by immunohistology. Specific monoclonal antibodies (mAb) against the three cytoplasmic CK isozymes of Xenopus laevis were isolated and characterized. Two of these mAbs, anti-CK-IV (DM16) and anti-CK-III (JRM4), were specific for CK-IV and CK-III subunits respectively, as well as for the corresponding homodimeric isozymes, CK-IV/IV and CK-III/III. Anti-CK-II (MRX7) mAb recognizes CK-II subunits and CK-II/III heterodimers; the homodimeric CK-II/III does not occur. Immunohistological localization on larval and adult tissue sections reveals that CK-IV epitopes, beside a generalized tissue distribution, are especially concentrated in the cytoplasm of some particular cells such as the photoreceptors in the outer segment of the retina, certain nerve cells of the spinal cord and spinal ganglia, and in larval hepatocytes. The CK-III III isozyme is specifically expressed in skeletal muscle, its appearance and accumulation occurring in parallel with myoblast differentiation. The CK-II antigen is detected first at the time of metamorphosis is skeletal muscles, as well as in the heart, eyes and brain. In striated musculature the expression of CK-II subunits during metamorphosis results in almost complete replacement of CK-III/III homodimers by CK-II/III heterodimers, as indicated by the progressive masking of CK-III epitope and the corresponding appearance of CK-II antigen. In the adult eyes, CK-II antigens localize at the same particular site of photoreceptors as do CK-IV antigens. Since that antigen represents a heterodimeric CK-II/III isozyme, this implies the activation of both CK-II and CK-III genes, none of which is expressed in larval retina.     

tBid mediated activation of the mitochondrial death pathway leads to genetic ablation of the lens in Xenopus laevis

Xenopus is a well proven model for a wide variety of developmental studies, including cell lineage. Cell lineage in Xenopus has largely been addressed by injection of tracer molecules or by micro-dissection elimination of blastomeres. Here we describe a genetic method for cell ablation based on the use of tBid, a direct activator of the mitochondrial apoptotic pathway. In mammalian cells, cross-talk between the main apoptotic pathways (the mitochondrial and the death domain protein pathways) involve the pro-death protein BID, the active form of which, tBID, results from protease truncation and translocation to mitochondria. In transgenic Xenopus, restricting tBID expression to the lens-forming cells enables the specific ablation of the lens without affecting the development of other eye structures. Thus, overexpression of tBid can be used in vivo as a tool to eliminate a defined cell population by apoptosis in a developing organism and to evaluate the degree of autonomy or the inductive effects of a specific tissue during embryonic development.     

Ontogeny of the immune system in Xenopus

Abstract. The larvae and adults of genetically identical clones of Xenopus each produce different populations of antibodies to dinitrophenylated keyhole-limpet hemocyanin (DNP-KLH) upon immunization. The larvae and adults differed with regard to the affinity of their IgM antibodies and the isoelectric-focusing pattern of their low-molecular-weight-Ig (IgG equivalent) antibodies. The larval antibody repertoire for DNP was not changed by the addition of adult helper T cells. Thus, the expression of a larval repertoire is the result of a B-cell pool peculiar to larvae and is not influenced, except in its quantity, by adult T cells.