Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

Performance of GEM2 on the ELLPACK problem population

The Pilot global element program GEM2 MK1.0 has been used to solve the two-dimensional problems in the ELLPACK population of partial differential equation test problems. The performance achieved is summarized in this paper; special attention is paid to those problems which are singular or near singular, and for which comparisons have been published by Houstis and Rice.¹²     

Memory for emotional trait adjectives in clinically depressed youth

An experiment was conducted to examine memory for emotional trait adjectives in depressed children and adolescents. Two groups of children and adolescents, clinically depressed participants and non-clinical controls, were compared on computerized versions of recall and recognition memory tasks. Three groups of words (positive trait adjectives, negative trait adjectives, and categorized neutral words) were used in the experiment. Results showed that the depressed group recalled significantly more negative adjectives than positive adjectives, whereas the control group recalled the same number of positive and negative adjectives. This effect was predicted by the association between age and level of depression, with the depression-related bias becoming stronger with age. Signal detection analysis revealed that the depressed group did not show any bias in the recognition task. The findings are discussed with respect to cognitive theories of depression with consideration of the developmental implications.     

Skin diseases in Bamako (Mali)

BACKGROUND: Skin diseases have only recently been considered as a possible public health problem in developing countries. Data supporting this matter are scarce. The aim of this study is to report the experience of a specialized dermatologic center in Bamako (Mali) in order to complete two previous studies conducted in the Bamako area: a prevalence study in the general population and a study in nonspecialized health centers of Bamako. It is our intention to provide a comprehensive picture of the problem of skin diseases in an African developing country. METHODS: We retrospectively collected all cases of skin diseases diagnosed during consultations provided at the Institut Marchoux in Bamako, the only center specializing in dermatology in Mali, during the year 1993. RESULTS: A total of 10,575 new outpatients were seen with 10,889 skin diseases. The main skin diseases registered were as follows: infectious dermatoses (41% of all diagnoses, including scabies (16.6%), superficial mycoses (13.6%), and primary pyoderma (5.6%)), dermatitis (20.4%), papular urticaria (4.4%), acne (4.2%), pityriasis alba (3.6%), keratoderma (3.6%), and urticaria (3%). Typical tropical infectious diseases accounted for only 1% of all diagnoses. CONCLUSIONS: It appears that certain skin diseases (mainly scabies and pyoderma) are an important health problem for the population of the Bamako area. Public health policies should be implemented in order to manage this problem rationally.     

Epidemiology of clonorchiasis in Ninh Binh Province, Vietnam

We present the spatial structure of binase, a small extracellular ribonuclease, derived from 1H-NMR* data in aqueous solution. The total of 20 structures were obtained via torsion angle dynamics using DYANA program with experimental NOE and hydrogen bond distance constraints and phi and chi1 dihedral angle constraints. The final structures were energy minimised with ECEPP/2 potential in FANTOM program. Binase consists of three alpha-helices in N-terminal part (residues 6-16, 26-32 and 41-44), five-stranded antiparallel beta-sheet in C-terminal part (residues 51-55, 70-75, 86-90, 94-99 and 104-108) and two-stranded parallel beta-sheet (residues 22-24 and 49-51). Three loops (residues 36-39, 56-67 and 76-83), which play significant role in biological functioning of binase, are flexible in solution. The differences between binase and barnase spatial structures in solution explain the differences in thermostability of binase, barnase and their hybrids.     

Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila

Gonadogenesis in the Drosophila embryo is a complex process involving numerous cellular migratory steps and cell-cell interactions. The mechanisms guiding germ cells to move through, recognize and adhere to specific cell types are poorly understood. In order to identify genes that are required for these processes, we have conducted an extensive mutagenesis of the third chromosome and screened for mutations disrupting germ cell migration at any point in embryonic development. Phenotypic analysis of these mutants demonstrates that germ cell migration can be broken down into discrete developmental steps, with each step requiring a specific set of genes. Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad. Moreover, mutations that we isolated affecting embryonic patterning as well as germ cell migration suggest that the origin of gonadal mesoderm lies within the eve domain of the developing mesoderm.     

Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort

OBJECTIVE: To identify whether obstetric and perinatal factors are independent predictors of child behaviour at 5 years. METHODOLOGY: The Mater University Study of Pregnancy (MUSP) is a prospective cohort study of 8556 mothers enrolled in early pregnancy. The relationship of obstetric and perinatal factors, maternal lifestyle, age and gender of the child, and social disadvantage were examined as predictors of child behaviour in 5005 children completing a modified child behaviour checklist at 5 years. This checklist contained three independent groups of behaviour: externalizng, internalizing and SAT (social, attentional and thought problems). RESULTS: In the initial analysis a limited number of associations were present. After adjusting for measures of social disadvantage, only number of antenatal admissions was associated with child behaviour in all three scales, while maternal cigarette smoking in pregnancy and male gender were associated with externalising and SAT behaviours. CONCLUSIONS: Most common epidemiologic obstetric and perinatal risk factors were not independent predictors of behaviour problems in children at 5 years.