No interaction between the serotonin transporter polymorphism (5-HTTLPR) and childhood adversity or recent stressful life events on symptoms of depression: results from two community surveys.

In this study we investigated interactions between the 5-HTTLPR genotype and environmental risk factors (G x E) on symptoms of depression in two large Australian community samples of adolescents and young adults. We postulated that a significant interaction between the 5-HTTLPR genotype and environmental risk factors of childhood adversity or stressful life events on symptoms of depression would be observed in subjects with at least one short allele (s/l or s/s) compared with subjects with no short alleles (l/l). We did not find significant G x E interactions between the 5-HTTLPR genotype and recent stressful life events or childhood adversity on symptoms of depression in our sample populations. However, we did find adolescents aged 17-18 years homozygous for the long allele (l/l) and exposed to persistently high levels of family adversity over a 6-year period were at a greater risk of depression than subjects with the same genotype exposed to no or persistently low levels of family adversity. This interaction should be interpreted cautiously due to the small number of depressed subjects in the sample with persistently high levels of family adversity.     

The dragon lizard <Emphasis Type="Italic">Pogona vitticeps</Emphasis> has ZZ/ZW micro-sex chromosomes

The bearded dragon, Pogona vitticeps (Agamidae: Reptilia) is an agamid lizard endemic to Australia. Like crocodilians and many turtles, temperature-dependent sex determination (TSD) is common in agamid lizards, although many species have genotypic sex determination (GSD). P. vitticeps is reported to have GSD, but no detectable sex chromosomes. Here we used molecular cytogenetic and differential banding techniques to reveal sex chromosomes in this species. Comparative genomic hybridization (CGH), GTG- and C-banding identified a highly heterochromatic microchromosome specific to females, demonstrating female heterogamety (ZZ/ZW) in this species. We isolated the P. vitticeps W chromosome by microdissection, re-amplified the DNA and used it to paint the W. No unpaired bivalents were detected in male synaptonemal complexes at meiotic pachytene, confirming male homogamety. We conclude that P. vitticeps has differentiated previously unidentifable W and Z micro-sex chromosomes, the first to be demonstrated in an agamid lizard. Our finding implies that heterochromatinization of the heterogametic chromosome occurred during sex chromosome differentiation in this species, as is the case in some lizards and many snakes, as well as in birds and mammals. Many GSD reptiles with cryptic sex chromosomes may also prove to have micro-sex chromosomes. Reptile microchromosomes, long dismissed as non-functional minutiae and often omitted from karyotypes, therefore deserve closer scrutiny with new and more sensitive techniques.     

Heterogeneity of HLA-A2 in Asia-Oceanic populations

HLA-A2 is one of the most common yet most diversified HLA antigens with 17 subtypes so far identified at the molecular level. A2 subtyping may have significant impact on clinical medicines. We developed a PCR/SSO-based comprehensive typing protocol for HLA-A and investigated the distribution of A2 alleles in regional ethnic groups. A2 was detected with high frequencies in most study populations. A total of 480 A2+ samples were identified and subtyped. The gene frequencies of A2 ranged from 34% in Chinese, 29% in Australian Caucasoids, 21% in Polynesians, 14% in Javanese and 13% in Australian Aborigines. However, in Melanesians and Micronesians A2 was absent. Six A2 alleles were found in the present experiments including A^*0201, 0203, 0205, 0206, 0207 and 0210. In Aborigines all the A2+ donors were typed as 0201. In Caucasoids A^*0201 accounted for 95% of A2+ samples though other three subtypes A^*0203, 0205 and 0207 were also detected. Extraordinary A2 heterogeneity was observed in Asia-Pacific populations where A^*0201 has become a minority. In Chinese all the six A2 alleles were discovered with A^*0201, 0203, 0206 and 0207 as the four major ones. In Javanese A2 was equally divided into A^*0201, 0203 and 0206 while in Polynesians A2 is overwhelmingly dominated by the oriental A^*0206 (71%). Our study also showed that comprehensive DNA matching for A2 would eliminate most A mismatches in the unrelated-donor transplantation in study populations.     

About some biochemical properties of dimethylsulfoxide and three of its homologues: Is the acidic function essential for nonsteroidal antiinflammatory activities?

Dimethylsulfoxide and three related sulfoxides exhibit some of the biochemical properties of classical non steroidal antiinflammatory acidic drugs. Thusn-propyl sulfoxide,n-butyl sulfoxide and tetramethylene sulfoxide stimulate O₂ consumption by rat liver mitochondria. These 3 compounds induce mitochondrial swelling. Lymphocyte welling is only induced by high doses ofn-propyl sulfoxide andn-butyl sulfoxide and not by tetramethylene sulfoxide.These sulfoxides induce changes in membrane permeability of various lymphocytes to ions by increasing⁴⁵Ca,⁸⁶Rb,¹³⁴Cs and²²Na fluxes across these membranes, the direction and the magnitude of which are dependent on the ionic composition of the medium and sulfoxide concentration.They all inhibit the incorporation of³H-thymidine,³H-uridine and¹⁴C-aminoacids into lymphocytes DNA, RNA and proteins.The relevance of such biochemical properties for analgesic or antiinflammatory clinical effects is discussed.     

A mobile group II intron of a naturally occurring rearranged mitochondrial genome in Kluyveromyces lactis

Summary Mitochondrial intron content is variable in the yeast Kluyveromyces lactis. Strains can be divided into three classes depending on the structure of the cytochrome oxidase subunit 1 (COX1) gene: (1) those containing intron K1 cox1.1, (2) those containing K1 cox1.2, 3 and 4 and, (3) those that contain all four introns. In addition, strains belonging to the first class (designated Type B strains), have an altered mitochondrial gene order relative to strains from classes (2) and (3) (Type A, Hardy et al. 1989). Crossing experiments reveal that K1 cox1.1 (a group II intron) transfers at high frequency (89%) to mitochondrial genomes lacking this intron. By contrast, the mobility of the remaining introns (all group I) is of the order of 7%.     

Direction-selective neurons in the optokinetic system with long-lasting after-responses

We describe the responses during and after motion of slow cells, which are a class of direction-selective neurons in the pretectal nucleus of the optic tract (NOT) of the wallaby. Neurons in the NOT respond to optic flow generated by head movements and drive compensatory optokinetic eye movements. Motion in the preferred direction produces increased firing rates in the cells, whereas motion in the opposite direction inhibits their high spontaneous activities. Neurons were stimulated with moving spatial sinusoidal gratings through a range of temporal and spatial frequencies. The slow cells were maximally stimulated at temporal frequencies <1 Hz and spatial frequencies of 0.13-1 cpd. During motion, the responses oscillate at the fundamental temporal frequency of the grating but not at higher-order harmonics. There is prolonged excitation after preferred direction motion and prolonged inhibition after anti-preferred direction motion, which are referred to as same-sign after-responses (SSARs). This is the first time that the response properties of neurons with SSARs have been reported and modeled in detail for neurons in the NOT. Slow cell responses during and after motion are modeled using an array of Reichardt-type motion detectors that include band-pass temporal prefilters. The oscillatory behavior during motion and the SSARs can be simulated accurately with the model by manipulating time constants associated with temporal filtering in the prefilters and motion detectors. The SSARs of slow cells are compared with those of previously described direction-selective neurons, which usually show transient inhibition or excitation after preferred or anti-preferred direction motion, respectively. Possible functional roles for slow cells are discussed in the context of eye movement control.     

Development of dendritic cells from GM-CSF-/- mice in vitro : GM-CSF enhances production and survival of cells

The production of dendritic cells (DC) from haemopoietic progenitors maintained in long term stroma-dependent cultures (LTC) of spleen or bone marrow (BM) occurs independently of added granulocyte/macrophage colony stimulating factor (GM-CSF). The possibility that cultures depend on endogenous GM-CSF produced in low levels was tested by attempting to generate LTC from spleen and BM of GM-CSF-/- mice. Multiple cultures from GM-CSF-/- and wild type mice were established and compared for cell production. GM-CSF-/- LTC developed more slowly, but by 16 weeks produced cells resembling DC in numbers comparable to wild type cultures. LTC maintained distinct populations of small and large cells, the latter resembling DC. Cells collected from GM-CSF-/- LTC were capable antigen presenting cells (APC) for T cell stimulation and morphologically resembled DC. Large cells expressed the CD11b, CD11c, CD86, 33D1 and Dec-205 markers of DC. Addition of GM-CSF to GM-CSF-/- LTC increased the proportion of large, mature DC present in culture. Stromal cells from GM-CSF-/- LTC could support the differentiation of DC from early progenitors maintained in LTC without addition of GM-CSF. However, GM-CSF is not a critical factor in the in vitro generation of DC from progenitors. It can, however, substitute for stromal cells in increasing the survival of mature DC.     

Evidence for the presence of a histaminergic neuron system in the rat brain: an immunohistochemical analysis

The binding of calcium antagonists in the rat hippocampal formation was studied using autoradiography. Hippocampal slices were labeled in vitro with [3H]PN 200-110. High densities of binding sites for calcium antagonists were found in the molecular layer of the dentate gyrus and in the CA3 subfield of the hippocampus. After ablation of the granule cells by local injection of colchicine a marked decrease in the number of [3H]PN 200-110 binding sites density was observed on these areas, while binding to other parts of the hippocampal formation and brain was spared. These results strongly suggest the localization of high densities of calcium channels to the granule cells of the dentate gyrus.