Differential influences of early growth and social factors on young children's cognitive performance in four low-and-middle-income birth cohorts (Brazil, Guatemala, Philippines, and South Africa).

BACKGROUND: Studies relating childhood cognitive development to poor linear growth seldom take adequate account of social conditions related to both, leading to a focus on nutrition interventions. We aimed to assess the roles of both biological and social conditions in determining early childhood cognition, mediated by birthweight and early linear growth. METHODS: After exploratory structural equation modelling to identify determining factors, we tested direct and indirect paths to cognitive performance through birthweight and child height-for-age at 2 years, assessed between 4 and 8.5 years of age among 2448 children in four birth cohort studies in low-and-middle-income countries (Brazil, Guatemala, Philippines and South Africa). Determinants were compared across the cohorts. FINDINGS: Three factors yielded excellent fit, comprising birth endowment (primarily maternal age and birth order), household resources (crowding, dependency) and parental capacity (parental education). We estimated their strength together with maternal height in determining cognitive performance. Percentage shares of total effects of the four determinants show a marked transition from mainly biological determinants of birth weight (birth endowment 34%) and maternal height (30%) compared to household resources (25%) and parental capacity (11%), through largely economic determinants of height at 2 years (household resources (60%) to cognitive performance being predominantly determined by parental capacity (64%) followed by household resources (29%). The largely biological factor, birth endowment (maternal age and birth order) contributed only 7% to childhood cognitive performance and maternal height was insignificant. In summary, the combined share of social total effects (household resources and parental capacity) rises from 36∙2% on birth weight, to 78∙2% on height for age at 24 m, and 93∙4% on cognitive functioning. INTERPRETATION: Across four low- and middle-income contexts, cognition in childhood is influenced more by the parental capacity of families and their economic resources than by birth weight and early linear growth. Improving children's cognitive functioning requires multi-sectoral interventions to improve parental education and enhance their economic wellbeing, interventions that are known to improve also early childhood growth.

Caveolin isoform expression during differentiation of C6 glioma cells.

Caveolae, a specialized form of lipid rafts, are cholesterol- and sphingolipid-rich membrane microdomains implicated in potocytosis, endocytosis, transcytosis, and as platforms for signal transduction. One of the major constituents of caveolae are three highly homologous caveolin isoforms (caveolin-1, caveolin-2, and caveolin-3). The present study expands the analysis of caveolin isoform expression in C6 glioma cells. Three complementary approaches were used to assess their differential expression during the dibutyryl-cyclic AMP-induced differentiation of C6 cells into an astrocyte-like phenotype. Immunoblotting, conventional RT-PCR, and real-time RT-PCR analysis established the expression of the caveolin-3 isoform in C6 cells, in addition to caveolin-1 and caveolin-2. Similar to the other isoforms, caveolin-3 was associated with light-density, detergent-insoluble caveolae membrane fractions obtained using sucrose-density gradient centrifugation. The three caveolin isoforms display different temporal patterns of mRNA/protein expression during the differentiation of C6 cells. Western blot and real-time RT-PCR analysis demonstrate that caveolin-1 and caveolin-2 are up-regulated during the late stages of the differentiation of C6 cells. Meanwhile, caveolin-3 is gradually down-regulated during the differentiation process. Indirect immunofluorescence analysis via laser-scanning confocal microscopy reveals that the three caveolin isoforms display similar subcellular distribution patterns. In addition, co-localization of caveolin-1/caveolin-2 and caveolin-1/caveolin-3 was detected in both C6 glioma phenotypes. The findings reveal a differential temporal pattern of caveolin gene expression during phenotypic differentiation of C6 glioma cells, with potential implications to developmental and degenerative events in the brain.

Identification of caveolae and caveolin in C6 glioma cells.

Caveolae (CAV) constitute a novel subcellular transport vesicle that has received special attention based on its proven and postulated participation in transcytosis, potocytosis, and in cell signaling events. One of the principal components of CAV are caveolin protein isoforms. Here, we have undertaken the immunochemical identification of CAV and the known caveolin isoforms (1alpha, 1beta, 2 and 3) in cultured rat C6 glioma cells. Immunoblot analysis revealed that particulate fractions from rat C6 glioma cells express caveolin-1 and caveolin-2. The relative detergent-insolubility of these caveolin isoforms was also determined by Western blot analysis. Indirect immunofluorescence analysis with caveolin-1 and -2 antibodies revealed staining patterns typical of CAV's known subcellular distribution and localization. For both caveolin isoforms immunocytochemical staining was characterized by intensely fluorescent puncta throughout the cytoplasm and diffuse micropatches at the level of the plasmalemma. Perinuclear staining was also detected, consistent and suggestive of caveolin's localization in the trans Golgi region. The caveolin-1 and -2 immunoreactivity seen in Western blots and immunocytochemically is related to structurally relevant CAV as supported by the isolation of caveolin-enriched membrane complexes using two different methods. Light-density, Triton X-100-insoluble caveolin-1- and caveolin-2-enriched fractions were obtained after fractionation of rat C6 glioma cells and their separation over 5-40% discontinuous sucrose-density gradients. Similar fractions were obtained using a detergent-free, sodium carbonate-based fractionation method. These results further support the localization of CAV and caveolins in glial cells. In addition, they demonstrate that cultured C6 glioma cells can be useful as a model system to study the role of CAV and caveolins in subcellular transport and signal transduction events in glial cells and the brain.

Caveolae a new subcellular transport organelle.

Recent advances have allowed the identification and characterization of well defined vesicular subcellular organelles involved in multiple basic cellular physiological processes, with demonstrated clinical relevance. Among these, three particular subcellular organelles have received special attention based on their proven and postulated participation in the sorting and targeting of small-and large-molecular weight molecules during exocytosis and endocytosis, and in cell signaling and transduction events. These have characteristic proteinaceous coat structures that allows their classification accordingly, into what has been described as clathrin coated vesicles and COP-coated vesicles and caveolae. In this review article a brief description of clathrin-coated vesicles and COP-coated vesicles is presented. Caveolae (CAV), in turn, constitute a novel subcellular organelle that has received special attention based on its proven and postulated participation in transcytosis, potocytosis, and in cell signaling and transduction events. In this review of the literature a more extensive discussion is presented of CAV. In this context the article discusses the structural features of caveolae, its constituent protein caveolin(s), the functional aspects of this new organelle, and its postulated clinical relevance.

Artefactos y artificios frecuentes en tomografía computada y resonancia magnética / Common artefacts in computed tomography and magnetic resonance imaging

Hay una gran variedad de artefactos en imágenes que se producen por la interacción entre los equipos y el paciente. Reconocerlos es importante, ya que pueden inducir informes erróneos o encubrir una patología. Por ello, una vez detectados, es necesario emplear técnicas para su eliminación. Describimos los artefactos más frecuentes en tomografía computada y resonancia magnética.

A wide variety of artefacts are observed in diagnostic imaging. They are caused by the interaction between the equipment and the patients. To recognise them is important, because they can induce pitfalls in the reports or mask some disease. Once they have been detected, it is necessary to apply techniques in order to elimínate them. A description is presented of the most common artefacts in computed tomography and magnetic resonance imaging.

Uptake and distribution of 2',3'-dideoxyinosine and its derivatives in a human monocytoid cell line.

The dideoxynucleoside analogue 2',3'-dideoxyinosine (ddI) has been used in the clinic as an alternative drug to zidovudine (AZT) in the treatment of patients with the acquired immunodeficiency syndrome (AIDS). However, it shows significant and variable toxicity in patients. It is known that various dideoxynucleoside analogues can cause the termination of the DNA chain following incorporation of the corresponding triphosphate metabolite by the polymerases. In the case of ddI, the presumed active metabolite is 2',3'-dideoxyadenosine 5'-triphosphate (ddATP). In order to understand the molecular basis for the toxicity of ddI, we evaluated the relationship between the intracellular formation of ddATP, its incorporation into cellular DNA and the effects on the growth of U937 cells, a human monocytoid cell line. Dideoxyinosine was not significantly toxic to U937 cells at concentrations as high as 500 microM in a 72 hrs. growth inhibition assay. The results of the uptake of 3HddI in this cell line showed a proportional increase in total metabolites with increasing concentrations of the drug (1-20 microM) after a 24 hrs. exposure. Incubation with 10 microM 3HddI resulted in the formation of low levels of ddATP within a period of 2 hrs. A significant amount of ddI-derived radioactivity was found in both DNA and RNA after exposure to 10 microM 3HddI for 24 to 72 hrs. However, no evidence of incorporation of ddATP into the cellular DNA fraction was obtained in these experimental conditions. Therefore, the lack of significant toxicity of ddI to U937 cells can be explained, at least in part, by its inability to incorporate ddATP into its cellular DNA at the doses studied.

Caveolae a new subcellular transport organelle

Recent advances have allowed the identification and characterization of well defined vesicular subcellular organelles involved in multiple basic cellular physiological processes, with demonstrated clinical relevance. Among these, three particular subcellular organelles have received special attention based on their proven and postulated participation in the sorting and targeting of small-and large-molecular weight molecules during exocytosis and endocytosis, and in cell signaling and transduction events. These have characteristic proteinaceous coat structures that allows their classification accordingly, into what has been described as clathrin coated vesicles and COP-coated vesicles and caveolae. In this review article a brief description of clathrin-coated vesicles and COP-coated vesicles is presented. Caveolae (CAV), in turn, constitute a novel subcellular organelle that has received special attention based on its proven and postulated participation in transcytosis, potocytosis, and in cell signaling and transduction events. In this review of the literature a more extensive discussion is presented of CAV. In this context the article discusses the structural features of caveolae, its constituent protein caveolin(s), the functional aspects of this new organelle, and its postulated clinical relevance