Observed Defects (observed + defect)

Distribution by Scientific Domains


Selected Abstracts


Expression of a non-DNA-binding Ikaros isoform exclusively in B cells leads to autoimmunity but not leukemogenesis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007
Heather Wojcik
Abstract Ikaros is a transcriptional regulator whose function is essential for B cell development. It is expressed in the hematopoietic stem cell (HSC) through the mature B cell stage. Using genetically engineered mice in which the endogenous Ikaros gene is disrupted, it has been shown that a lack of Ikaros leads to a block in B cell development and that its severe diminution results in a hyperresponsive B cell compartment. Ikaros expression within the HSC has led to speculation as to whether the role of Ikaros in B cell biology is largely accomplished prior to B cell specification. In addition, widespread expression of Ikaros in hematopoietic cells leads to the possibility that some or all of the observed defects are not B cell autonomous. In this report, we demonstrate that over-expression of a dominant interfering Ikaros isoform exclusively in B cells has profound effects on mature B cell function. We provide evidence that continued high-level expression of Ikaros is essential for homeostasis of peripheral lymphocytes and maintenance of B cell tolerance. We also show that deregulation of Ikaros activity does not rapidly result in B cell leukemogenesis as it does with 100% penetrance within the T cell lineage. [source]


The aetiology of sperm protamine abnormalities and their potential impact on the sperm epigenome

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2008
Douglas T. Carrell
Summary During the elongating spermatid stage of spermatogenesis, there is a step-wise replacement of nuclear histones with protamines 1 and 2. In fertile men, the ratio of protamine 1/protamine 2 (P1/P2) is within the narrow range of 0.8,1.2. Ratios above or below that range are associated with infertility, exhibiting a wide range of defects including decreased sperm counts, morphology, fertilization ability, and embryo implantation capacity. In this review, we highlight studies evaluating potential causes of abnormal protamine expression, including the sequencing of genes relevant to protamine expression in both affected patients and controls. While the variants of the protamine genes themselves do not appear to be responsible for most observed defects, variants of the Contrin gene, a transcription factor and translation repressor, appear to be contributory to some cases of abnormal expression. Additionally, we explore the potential effects of abnormal protamine replacement on the epigenome of human sperm. Ongoing studies are evaluating the role of retained histones and DNA methylation in sperm, which may be affected in sperm with aberrant protamine replacement. This important area of epigenetic research has profound clinical implications. [source]


Graphite under the magnetic force microscope

PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 11 2007
T. L. Makarova
Abstract In search for magnetically active carbon structures, we have undertaken the magnetic force microscopy study of intrinsic defects at the surface of highly oriented pyrolytic graphite. Most of the observed defects, such as ridges and cleavage edges, are found magnetically inert. However, some of the observed sharp cleavage edges do show magnetic activity , a built-in surface magnetization, which reveals itself as the magnetic force gradient signal sensitive to the polarity of the tip magnetization. These results indicate the existence of a defect related magnetism at room temperature on graphite surface. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


Diffraction and imaging study of imperfections of crystallized lysozyme with coherent X-rays

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2004
Z. W. Hu
Phase-contrast X-ray diffraction imaging and high-angular-resolution diffraction combined with phase-contrast radiographic imaging were employed to characterize defects and perfection of a uniformly grown tetragonal lysozyme crystal in the symmetric Laue case. The full-width at half-maximum (FWHM) of a 4,4,0 rocking curve measured from the original crystal was ,16.7,arcsec and imperfections including line defects, inclusions and other microdefects were observed in the diffraction images of the crystal. The observed line defects carry distinct dislocation features running approximately along the ,1,1,0, growth front and have been found to originate mostly in a central growth area and occasionally in outer growth regions. Inclusions of impurities or formations of foreign particles in the central growth region are resolved in the images with high sensitivity to defects. Slow dehydration led to the broadening of a fairly symmetric 4,4,0 rocking curve by a factor of ,2.6, which was primarily attributed to the dehydration-induced microscopic effects that are clearly shown in X-ray diffraction images. The details of the observed defects and the significant change in the revealed microstructures with drying provide insight into the nature of imperfections, nucleation and growth, and the properties of protein crystals. [source]