An integrated genetic/RFLP map of the Arabidopsis thaliana genome

We have assembled an integrated genetic/restriction fragment length polymorphism (RFLP) linkage map of the nuclear genome of the flowering plant Arabidopsis thaliana . The map is based on two independent sets of RFLP data, RFLP data for 123 new markers, and pair-wise segregation data of 125 classical genetic markers. Mathematical integration of the independent data sets was performed using the joinmap computer package. Sixty-two markers common to two or more data sets were exploited to facilitate integration of the individual maps. The current map, which encompasses a total genetic distance of 520 cM, contains 125 classical genetic markers and 306 RFLP markers. Comparison of the integrated consensus map with the individual maps demonstrates that the overall linear order of the integrated map is in good agreement with the component maps. It must be emphasized, however, that the integrated map represents the 'best fit' which is clearly subject to the statistical limitations of the available data. We present several examples where local differences in map order are observed between the integrated and component maps. It is likely, given the problems associated with statistical integration of mapping data from different populations, that the integrated map will contain additional local inconsistencies and problematic regions. None the less, the unified map provides a framework for building an increasingly accurate and useful map. Subsequent refinements of the map will be available electronically end researchers are invited to submit revised map data to the corresponding author for inclusion in future updates (see Appendix 1).     

Sex-linked hereditary thrombocytopenia with immunological defects.

14 cases of severe thrombocytopenia in one family are presented. Case histories, clinical examination, analyses of platelets, haemoglobin, reticulocytes, leucocytes, eosinophilocytes, differential counts of leucocytes, serum immunoglobulin IgA, IgM, IgG, IgE concentrations, complement fixing platelet antibodies, isohaemagglutinins, colour perception, determination of red cell and serum groups as well as HL-A types were obtained from a total of 59 members of the family. The in vitro blast transformation response of blood lymphocytes was studied in 6 patients and 45 relatives. The pattern of transmission of the disease was in full agreement with X-linked recessive inheritance. Investigation of the immune system revealed impaired responses to microbial antigens in the 6 patients so studied. All relatives examined had normal haematological status, whereas approximately half showed a subnormal response to one microbial extract. The low responders were evenly distributed within the family, and it was not possible to correlate low response and presumed carrier state.     

Recent advances in the immunogenetics of idiopathic inflammatory myopathy

This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.     

Bone Formation and Resorption Are Both Increased in Experimental Autoimmune Arthritis

Introduction

Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. We evaluated how bone formation and bone resorption are altered in experimental autoimmune arthritis.

Methods

Twenty-one female SKG mice were randomized to either an arthritis group or a control group. Tetracycline was used to identify mineralizing surfaces. After six weeks the right hind paws were embedded undecalcified in methylmethacrylate. The paws were cut exhaustively according to the principles of vertical sectioning and systematic sampling. 3D design-based methods were used to estimate the total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast-covered bone surfaces. In addition the presence of adjacent inflammation was ascertained.

Results

The total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast covered surfaces were elevated in arthritic paws compared to normal paws. Mineralizing surfaces were elevated adjacent to as well as not adjacent to inflammation in arthritic mice compared to normal mice. In arthritic mice, eroded surfaces and osteoclast covered surfaces were larger on bone surfaces adjacent to inflammation than on bone surfaces without adjacent inflammation. However, we found no difference between mineralizing surfaces at bone surfaces with or without inflammation in arthritic mice.

Conclusions

Inflammation induced an increase in resorptive bone surfaces as well as formative bone surfaces. The bone formative response may be more general, since formative bone surfaces were also increased when not associated with inflammation. Thus, the bone loss may be the result of a substantial local bone resorption, which cannot be compensated by the increased local bone formation. These findings may be valuable for the development of new osteoblast targeting drugs in RA.     

Intraclonal variation in RNA viruses: generation, maintenance and consequences

This paper explores the evolutionary implications of the enormous variability that characterizes populations of RNA viruses and retroviruses. It begins by examining the magnitude of genetic variation in both natural and experimental populations. In natural populations, differences arise even within individual infected patients, with the per-site nucleotide diversity at this level ranging from < 1% to 6%. In laboratory populations, two viruses sampled from the same clone differed by ∼0.7% in their fitness. Three different mechanisms that may be important in maintaining viral genetic variability were tested: (1) Fisher's fundamental theorem, to compare the observed rate of fitness change with the extent of fitness-related variation within the same experimental populations; (2) magnitude of genomic mutation rate, to assess whether it correlated with fitness-related variation, as predicted by the mutation-selection balance hypothesis; (3) frequency-dependent selection, which affords rare genotypes an advantage. The paper concludes with a discussion of two evolutionary consequences of variability: the fixation of deleterious mutations by drift in small populations and the role of clonal interference in large ones.  © 2003 The Linnean Society of London. Biological Journal of the Linnean Society , 2003, 79 , 17–26.     

Rapid Two-Step Procedure for Large-Scale Purification of Pediocin-Like Bacteriocins and Other Cationic Antimicrobial Peptides from Complex Culture Medium

A rapid and simple two-step procedure suitable for both small- and large-scale purification of pediocin-like bacteriocins and other cationic peptides has been developed. In the first step, the bacterial culture was applied directly on a cation-exchange column (1-ml cation exchanger per 100-ml cell culture). Bacteria and anionic compounds passed through the column, and cationic bacteriocins were subsequently eluted with 1 M NaCl. In the second step, the bacteriocin fraction was applied on a low-pressure, reverse-phase column and the bacteriocins were detected as major optical density peaks upon elution with propanol. More than 80% of the activity that was initially in the culture supernatant was recovered in both purification steps, and the final bacteriocin preparation was more than 90% pure as judged by analytical reverse-phase chromatography and capillary electrophoresis.