Case-control study of congenital malformations

To determine potentially teratogenic influencies in Belgrade, a group of 113 mothers who gave birth to severely malformed infants and a control group of 195 mothers with normal infants were interviewed using a structured questionnaire.Statistically significant differences between the two groups were found in the mother's family history of congenital malformations (P < 0.05) and the mother's diseases during the pregnancy (P < 0.01). Infections in the first trimester were particularly more prevalent in case mothers (OR = 7.70; P < 0.01). Mothers did not differ significantly according to exposure to organic solvents, supportive therapy during the pregnancy, use of oral contraceptives, or other personal habits.Corresponding author.     

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Human health risk assessment of lead,cadmium, and mercury co-exposure from agricultural soils in the Tuzla Canton (Bosnia and Herzegovina)

The aim of this study was to assess the risk of human exposure to lead (Pb), cadmium (Cd), and mercury (Hg) through agricultural soil by considering both uncertainty and variability in key exposure parameters. For this reason we collected soil samples from 29 locations in the Tuzla Canton (Bosnia and Herzegovina) and measured their metal levels with inductively coupled plasma atomic emission or absorption spectrometry (ICP-AES and ICP-AAS, respectively). The levels of Pb ranged from 13.33 to 1692.33 mg/kg, of Cd from 0.05 to 3.67 mg/kg, and of Hg from 0.02 to 2.73 mg/kg. To estimate cancer and non-cancer risks we used deterministic and semi-probabilistic methods. Lead was found to involve higher health risk than the other two heavy metals. Its hazard index (HI) decreased between population groups (children>women>men) and exposure routes (ingestion>skin contact>inhalation). Our Monte Carlo simulations indicated that Pb HIs for both adult populations had a 0.6 % probability to exceed the threshold value of 1, while in children this probability was 14.2 %. Cd and Hg showed no probability to exceed the threshold in any scenario. Our simulation results raise concern about possible adverse health effects of heavy metals from soil, especially in children. It is very important to continue monitoring environmental pollution and assess human health risk, not only with respect to soil, but also with other important environmental compartments, such as air and water.KEY WORDS: cancer risk, deterministic methodology, heavy metals, Monte Carlo simulations, non-cancer risk, probabilistic methodology     

Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ...     

Small-scale pattern formation in a cortical area of the embryonic chicken telencephalon

The parahippocampal area is a cortical region of the avian dorsomedial telencephalon. In the chicken embryo, it contains discrete clusters of cadherin-7-positive cells, which are embedded in a cadherin-7-negative matrix. In the present work, the development and spatial distribution of these clusters is studied in whole-mount specimens. The clusters form a complex, coherent pattern of patches of variable size, spacing, and staining intensity. The pattern is especially prominent and regularly spaced in the rostral part of the caudolateral parahippocampal area. Here, it consists of stripes and connecting bridges with an average periodicity of approximately 0.3 mm. This pattern vaguely resembles some animal fur patterns and the ocular dominance domain of the mammalian visual cortex. The cadherin-7-positive patches also differ from their surrounding area by their cytoarchitecture and their increased acetylcholinesterase activity, suggesting that they represent functionally specialized subregions within the parahippocampal area. During development, the patchiness is first observed between 9 and 10 days of incubation and gradually becomes more prominent until 15 days of incubation. Our results indicate that the patchy organization of cortical gray matter on a small scale of periodicity (below 1 mm), which is well studied in the mammalian neocortex, is also found in the avian telencephalon.