Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

German National Consensus Recommendations on Nutrition and Lifestyle in Pregnancy by the ‘Healthy Start - Young Family Network’

Diet and physical activity before and during pregnancy affect short- andlong-term health of mother and child. The energy needs at the end ofpregnancy increase only by about 10% compared to nonpregnant women. Anexcessive energy intake is undesirable since maternal overweight andexcessive weight gain can increase the risks for a high birth weight andlater child overweight and diabetes. Maternal weight at the beginning ofpregnancy is especially important for pregnancy outcome and childhealth. Women should strive to achieve normal weight already beforepregnancy. Regular physical activity can contribute to a healthy weightand to the health of pregnant women. The need for certain nutrientsincreases more than energy requirements. Before and during pregnancy,foods with a high content of essential nutrients should bepreferentially selected. Supplements should include folic acid andiodine, iron (in case of suboptimal iron stores), the omega-3 fatty aciddocosahexaenoic acid (in case of infrequent consumption of ocean fish)and vitamin D (in case of decreased sun exposure and decreasedendogenous vitamin D synthesis). Pregnant women should not smoke and notstay in rooms where others smoke or have smoked before (passivesmoking). Alcohol consumption should be avoided, since alcohol can harmunborn children

21-Hydroxylase Genotyping in Australasian Patients with Congenital Adrenal Hyperplasia

Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, 12 G splice and 1172N the most common. Five patients with a 1172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.

German National Consensus Recommendations on Nutrition and Lifestyle in Pregnancy by the ‘Healthy Start - Young Family Network’

Diet and physical activity before and during pregnancy affect short- andlong-term health of mother and child. The energy needs at the end ofpregnancy increase only by about 10% compared to nonpregnant women. Anexcessive energy intake is undesirable since maternal overweight andexcessive weight gain can increase the risks for a high birth weight andlater child overweight and diabetes. Maternal weight at the beginning ofpregnancy is especially important for pregnancy outcome and childhealth. Women should strive to achieve normal weight already beforepregnancy. Regular physical activity can contribute to a healthy weightand to the health of pregnant women. The need for certain nutrientsincreases more than energy requirements. Before and during pregnancy,foods with a high content of essential nutrients should bepreferentially selected. Supplements should include folic acid andiodine, iron (in case of suboptimal iron stores), the omega-3 fatty aciddocosahexaenoic acid (in case of infrequent consumption of ocean fish)and vitamin D (in case of decreased sun exposure and decreasedendogenous vitamin D synthesis). Pregnant women should not smoke and notstay in rooms where others smoke or have smoked before (passivesmoking). Alcohol consumption should be avoided, since alcohol can harmunborn children

Nuclear Reaction Network for Primordial Nucleosynthesis: a detailed analysis of rates, uncertainties and light nuclei yields

We analyze in details the standard Primordial Nucleosynthesis scenario. In particular we discuss the key theoretical issues which are involved in a detailed prediction of light nuclide abundances, as the weak reaction rates, neutrino decoupling and nuclear rate modeling. We also perform a new analysis of available data on the main nuclear processes entering the nucleosynthesis reaction network, with particular stress on their uncertainties as well as on their role in determining the corresponding uncertainties on light nuclide theoretical estimates. The current status of theoretical versus experimental results for 2H, 3He, 4He and 7Li is then discussed using the determination of the baryon density as obtained from Cosmic Microwave Background anisotropies.Comment: LaTeX, 83 pages, 30 .pdf figures. Some typos in the units of R-functions in appendix D and relative plots fixe

Helper T-cell kinetics and investigation of antigen receptor expression on early and memory T-helper cells.

The subcutaneous application of soluble antigen resulted in generation of helper T lymphocytes in the draining lymph nodes, tested 4 days after priming in the adoptive transfer system. Four days later a specific helper T-cell population was detected in the spleen. B-cell activity could be demonstrated 4-5 days after helper T-cell activity in both organs. We investigated the early helper T-cell population and memory T cells with respect to differences in the expression of antigen receptors. No such differences could be detected, either by anti-immunoglobulin-coated Degalan columns or by an antigen-specific rosetting method