Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment.

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.     

Transfer of enhanced resistance against Listeria monocytogenes induced with ribosomal RNA and the adjuvant dimethyldioctadecylammonium bromide

In this study we investigated the mechanism of enhanced resistance against Listeria monocytogenes induced with Listeria ribosomal RNA and the adjuvant dimethyldioctadecylammonium bromide (DDA). Mice immunized with DDA alone (which were not protected against Listeria-infection) were used as negative controls. Mice immunized with RNA plus DDA were found to have an increased capacity to mobilize polymorphonuclear leukocytes (PMNs) and macrophages to the inflamed peritoneal cavity compared to mice immunized with adjuvant alone. Intraperitoneal (i.p.) inflammation was induced by injection of the sterile irritant proteose peptone. The protective capacity of various cell-populations was investigated by i.p. transfer of cells to normal recipient mice and concomitant challenge of recipient animals with a lethal dose of viable Listeria. Inflammatory PMNs as well as inflammatory macrophages from mice immunized with RNA plus DDA protected recipient animals against listeriosis whereas cells from mice immunized with DDA alone failed to do so. Therefore, enhanced mobilization as well as activation of PMNs and macrophages may have contributed to the expression of protection against L. monocytogenes induced with RNA plus DNA.     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).     

Synthesis and characterization of poly-L-lysine with controlled low molecular weight

N-Carboxy-(N^?-benzyloxycarbonyl)-L -lysine anhydride (Z-L -lysine NCA) was polymerized in dimethylformamide with triethylamine, diethylamine or hexylamine as initiator, at varying molar ratios of NCA to initiator (M/I ratio). After removal of the protecting Z-group the resulting poly-L -lysine was characterized with ¹H NMR and MALDI TOF MS. Both diethylamine- and hexylamine-initiated polymerization yielded poly-L -lysine in which the initiators were incorporated at the carboxylic end of the polymer. This indicates that the NCA polymerization occurred exclusively via nucleophilic attack of the initiator on the monomer. On the other, hand, when triethylamine was used as the initiator, poly-L -lysine was obtained in which no triethylamine-derived end group could be detected by MS. These polymer chains are most likely end-capped with an N-acyl-2,5-dioxopiperazine group at the carboxylic end of the polymer. Incorporation of diethylamine and hexylamine allowed determination of the degree of polymerization (DP) of the obtained polymers by ¹H NMR. The DP depended linearly on the M/I ratio, for both diethylamine and hexylamine, with higher DPs for the diethylamine-initiated poly-L -lysine at equal M/I ratio.     

Properties of the tobacco mosaic virus intermediate length RNA-2 and its translation

The existence of subgenomic RNAs is well established in the case of plant viruses such as tobacco mosaic virus (TMV). However, except for the subgenomic coat protein mRNA, it is not known whether the other subgenomic RNAs have a function in the life cycle of the virus. In search of more information about one of the major subgenomic RNAs-intermediate length RNA-2 or I2 RNA-of TMV, in vitro and in vivo translational studies were performed. The I2 RNA, which codes in vitro for the synthesis of a 30K (K = kilodalton) protein, appears to be uncapped as judged by the need of different in vitro translation conditions for the synthesis of this protein, compared to the conditions required for the synthesis of the 126K and 183K proteins coded by the capped genomic RNA. In vivo a protein migrating in the same position as the 30K protein synthesized in vitro can be detected in infected tobacco leaves. Since this protein occurs transiently early upon infection, whether it is virus-coded or virus-induced, it could have an early function during infection.     

A second field metachronous Merkel cell carcinoma of the lip and the palatine tonsil confirmed by microarray-based comparative genomic hybridisation

Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour was localised to the upper lip and was in stage T2. After successful cryosurgery and a 7-year tumour-free period, a new tumour developed in her palatine tonsil. Histologically and immunohistochemically, this resembled the tumour in the lip. The regional lymph nodes were devoid of metastasis. The paraffin-embedded material of the two tumours and the unaffected lymphatic tissue were analysed with DNA microarrays for comparative genomic hybridisation to assess the genetic relationship of the tumours. In both tumours, regions on 2p and 10p were commonly over-represented, while 41 regions on chromosomes 1–4, 6, 8–9, 11 and 14–22 were commonly under-represented. Chromosomes 1, 3, 4, 16–18 and X were most frequently involved in the DNA losses. In gene copy numbers in the two tumours, 31 chromosome locations were found to be differently affected. The partly similar and partly different molecular patterns indicated a genetic relationship between the tumours and excluded the possibility that the tonsillar tumour was a metastasis. The findings suggest that a genetically altered field was the reason for the development of the tonsillar cancer; thus, it can be regarded pathogenetically as a second field tumour.     

Frequency domain models of the EEG

The structure of the normal resting EEG crosspectrum SVV(omega) is analyzed using complex multivariate statistics. Exploratory data analysis with Principal Component Analysis (PCA) is followed by hypothesis testing and computer simulations related to possible neural generators. The SVV(omega) of 211 normal individuals (ages 5 to 97) may be decomposed into two types of processes: the xi process with spatial isotropicity reflecting diffuse, correlated cortical generators with radial symmetry, and processes that seem to be generated by more spatially concentrated, correlated sources. The latter are reflected as spectral peaks such as the process. The eigenvectors of the xi process are the Spherical Harmonic Functions which explains the recurring pattern of maps characteristic of the spatial PCA of qEEG data. A new method for estimating sources in the frequency domain which fits dipoles to the whole crosspectrum is applied to explain the characteristics of the localized sources.