Scrapie-Specific Pathology of Sheep Lymphoid Tissues

Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrPd within endosomes and lysosomes. In addition, TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrPd is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrPd/cell membrane interactions occur in different cell types

An Atypical Form of αB-crystallin Is Present in High Concentration in Some Human Cataractous Lenses IDENTIFICATION AND CHARACTERIZATION OF ABERRANT N- AND C-TERMINAL PROCESSING

Two unique polypeptides, 22.4 and 16.4 kDa, were prominent in some human cataracts. Both proteins were identified as modified forms of the small heat shock protein, αB-crystallin. The concentration of total αB-crystallin in most of these cataracts was significantly increased. The 22.4-kDa protein was subsequently designated as αBg. Mass spectrometric analyses of tryptic and Asp-N digests showed αBg is αB-crystallin minus the C-terminal lysine. αBg constituted 10–90% of the total αB-crystallin in these cataracts and was preferentially phosphorylated over the typical form of αB-crystallin. Human αBg and αB-crystallin were cloned and expressed inEscherichia coli. The differences in electrophoretic mobility and the large difference in native pI values suggest some structural differences exist. The chaperone-like activity of recombinant human αBg was comparable to that of recombinant human αB-crystallin in preventing the aggregation of lactalbumin induced by dithiothreitol. The mechanism involved in generating αBg is not known, but a premature termination of the αB-crystallin gene was ruled out by sequencing the polymerase chain reaction products of the last exon for the αB-crystallin gene from lenses containing αBg. The 16.4-kDa protein was an N-terminally truncated fragment of αBg. The high concentration of αB-crystallin in these cataracts is the first observation of this kind in human lenses

The Schistosomiasis Research Agenda—What Now?

[Extract] As relatively new schistosomiasis researchers, we awaited with eagerness the publication of the "Schistosomiasis Research Agenda" SRA) put forward by Colley and Secor in the December 2007 issue of PLoS Neglected Tropical Diseases [1]. The SRA is a comprehensive, well-organized list of research activities that reflects the impressive diversity of interests that make up current schistosomiasis research. Colley and Secor went to admirable lengths to solicit the interests of researchers the world over, with special efforts to solicit the opinions of scientists in countries or regions where schistosomiasis is endemic, such as Brazil, China, and Africa. Having attended some of these meetings (11th International Congress of Parasitology, held in Glasgow, United Kingdom in August 2006; and the 55th Annual Meeting of the American Society of Tropical Medicine and Hygiene, held in Atlanta, United States in November 2006) and received the emails, we are confident that the SRA indeed reflects the richness and breadth of current schistosomiasis research

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

First GPS Baseline Results from the North Andes

The CASA UNO GPS (Global Positioning System) experiment (January-February 1988) has provided the first epoch baseline measurements for the study of plate motions and crustal deformation in and around the North Andes. Two dimensional horizontal baseline repeatabilities are as good as 5 parts in 108 for short baselines (100-1000km), and better than3 parts in 108 for long baselines (\u3e1000km). Vertical repeatabilities are typically 4 -6 cm, with a weak dependence on baseline length. The expected rate of plate convergence across the Colombia Trench is 6-8 cm/yr, which should be detectable by the repeat experiment planned for 1991. Expected deformation rates within the North Andes are of the order of 1 cm/yr, which may be detectable with the 1991 experiment

Charles Darwin and the Origin of Life

When Charles Darwin published The Origin of Species 150 years ago he consciously avoided discussing the origin of life. However, analysis of some other texts written by Darwin, and of the correspondence he exchanged with friends and colleagues demonstrates that he took for granted the possibility of a natural emergence of the first life forms. As shown by notes from the pages he excised from his private notebooks, as early as 1837 Darwin was convinced that “the intimate relation of Life with laws of chemical combination, & the universality of latter render spontaneous generation not improbable”. Like many of his contemporaries, Darwin rejected the idea that putrefaction of preexisting organic compounds could lead to the appearance of organisms. Although he favored the possibility that life could appear by natural processes from simple inorganic compounds, his reluctance to discuss the issue resulted from his recognition that at the time it was possible to undertake the experimental study of the emergence of life

Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure