T-cell proliferative response is controlled by loci Tria4 and Tria5 on mouse Chromosomes 7 and 9

Lymphocytes of mouse strains BALB/cHeA (BALB/c) and STS/A (STS) differ in their response to CD3 antibody (anti-CD3). We analyzed the genetic basis of this strain difference, using the Recombinant Congenic Strains (RCS) of the BALB/c-c-STS/Dem (CcS/Dem) series. Each of the 20 CcS/Dem strains carries a different, random combination of 12.5% genes from the nonresponding strain STS and 87.5% genes of the intermediate responder strain BALB/c. Differences in the magnitude of anti-CD3-induced response among CcS/Dem strains indicated that in addition to Fcγ receptor 2 (Fcgr2) other genes are involved in the control of this response as well, and we have already mapped loci Tria1 (T cell receptor-induced activation 1), Tria2, and Tria3. In order to map additional Tria genes, we tested F₂ hybrids between the high responder RC strain CcS-9 and the low responder strain CcS-11. Proliferation in complete RPMI medium without anti-CD3 is controlled by locus Sprol1 (spontaneous proliferation 1) linked to the marker D4Mit23 on Chr 4. At concentration 0.375 μg/ml anti-CD3 mAb, the response was controlled by a locus Tria4, which maps to the marker D7Mit32 on Chr 7. The response to the higher concentration of mAb, 3 μg/ml, was controlled by Tria5, which mapped to the marker D9Mit15 on Chr 9. Anti-CD3 is being used for modulation of lymphocyte functions in transplantation reactions and in cancer treatment. Study of mechanisms of action of different Tria loci could lead to better understanding of genetic regulation of these reactions. Received: 28 October 1998 / Accepted: 17 March 1999     

Female subsistence strategies among Ache hunter-gatherers of Eastern Paraguay

Anthropologists have frequently proposed that sexual division of labor is produced by childcare constraints on women's subsistence work. We present data on the forest activities of Ache women that show that differences in parental investment partially account for variation in food acquisition among individual women. Data also suggest that childcare constraints are important in understanding the sexual division of labor.     

Streptomyces coelicolor DNA homologous with acyltransferase domains of type I polyketide synthase gene complex

An acyltransferase-homologous DNA fragment was amplified in a PCR reaction on a cosmid DNA template from the genomic DNA library of the soil bacterium Streptomyces coelicolor A3(2). The putative amino acid sequence of the fragment resembles acyl-CoA:ACP acyltransferase domains from several bacterial enzymatic complexes of polyketide synthase. There is a high similarity with acyltransferase domains from so-called type I polyketide synthases. Such synthases catalyze production of the aglycone portion of macrolides and polyethers that are important as antibiotics or immunosuppressants. The amplified fragment is considered to be a part of a larger gene complex.     

Yeast and human mitochondrial helicases

Mitochondria are semiautonomous organelles which contain their own genome. Both maintenance and expression of mitochondrial DNA require activity of RNA and DNA helicases. In Saccharomyces cerevisiae the nuclear genome encodes four DExH/D superfamily members (MSS116, SUV3, MRH4, IRC3) that act as helicases and/or RNA chaperones. Their activity is necessary for mitochondrial RNA splicing, degradation, translation and genome maintenance. In humans the ortholog of SUV3 (hSUV3, SUPV3L1) so far is the best described mitochondrial RNA helicase. The enzyme, together with the matrix-localized pool of PNPase (PNPT1), forms an RNA-degrading complex called the mitochondrial degradosome, which localizes to distinct structures (D-foci). Global regulation of mitochondrially encoded genes can be achieved by changing mitochondrial DNA copy number. This way the proteins involved in its replication, like the Twinkle helicase (c10orf2), can indirectly regulate gene expression. Here, we describe yeast and human mitochondrial helicases that are directly involved in mitochondrial RNA metabolism, and present other helicases that participate in mitochondrial DNA replication and maintenance. This article is part of a Special Issue entitled: The Biology of RNA helicases — Modulation for life.     

Comparative analysis of RCAS1 level in neoplasms and placenta

The tumor associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expressed with high frequency in various cancer and trophoblast cells, inhibits growth of estrogen receptor-expressing cells and induces apoptosis. Because previous reports demonstrated RCAS1 presence only by non-quantitative immunocytochemistry methods, we decided to use a Western blotting with anti-RCAS1 monoclonal antibodies for estimation of the relative content of the tumor-associated antigen. One hundred tissue samples were assayed (neoplasms, chronic inflammatory diseases, healthy tissues, trophoblasts and placentas at term). RCAS1 was present in all neoplastic, placental and trophoblast tissue samples and its level in malignant samples was statistically significantly higher than in benign neoplasms. The amount of RCAS1 in chronic inflammations was also significantly increased in immune mediated diseases, like allergic nasal polyps and sarcoidosis. The RCAS1 protein was not revealed in healthy mucous membrane and in muscle tissues. The presented results suggest that RCAS1 might play an important role in tumor escape from host immunological surveillance and carry weight in the down regulation of the maternal immune response, thereby maintaining pregnancy.     

Transprotection of N-Benzoylated Nucleobase Derivatives by Dialkylaminomethylene Group

Abstract

The use of (chloromethylene)diakylammonium chloride in selective transprotection of N-benzoylated nucleobase derivatives is reported along with the evaluation of the stability of various protecting groups widely used in nucleoside and/or nucleotide chemistry.     

A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches

Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors’ opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.