Search

Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson’s and Alzheimer’s diseases, endocrine disruption, and cancer, but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown. Here we demonstrate, using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae, that dieldrin alters leucine availability. This model is supported by multiple lines of congruent evidence: (1) mutants defective in amino acid signaling or transport are sensitive to dieldrin, which is reversed by the addition of exogenous leucine; (2) dieldrin sensitivity of wild-type or mutant strains is dependent upon leucine concentration in the media; (3) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin; (4) leucine uptake is inhibited in the presence of dieldrin; and (5) dieldrin induces the amino acid starvation response. Additionally, we demonstrate that appropriate negative regulation of the Ras/protein kinase A pathway, along with an intact pyruvate dehydrogenase complex, is required for dieldrin tolerance. Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans.

The purpose of the paper is to evaluate the conformational and dimensional development of the hand and external ear of a group of children 3 to 6 years of age (240 children, 122 boys and 118 girls) from all the country, selected from the study of family and filiations. The data have been compared with Knussmann normality scales. The statistical signification was probed with Student t-test and Z-test. On the average, the auricle has a medium dimensions and conformation, while the hand has smaller dimensions and a medium conformation. The growth between 3 and 6 years is characteristic for this period, with irregular rhythm and low intensity sexual dimorphism, favoring the boys. The research represents a novelty for the Romanian auxological anthropology. The preschool age is a delicate ontogenetic period, contained in the Pende's "little puberty", and the development of the hand and external ear is very important for the future complex activity of the child, claiming the care and attention of the didactic staff. We consider that our study reveals its importance for the medical and educational system. [ABSTRACT FROM AUTHOR]

Diacronic and comparative anthropological study of some Romanian students from Bucharest universities. In the present paper we compare mean dimensional and conformational values which characterize four series of students from Bucharest universities (Medicine, Technology, Ecology) studied by Professor Francisc Rainer (1929), Th. Enăchescu and Suzana Grinţescu-Pop (1972, 1974) and Eleonora Luca (1996-1998). By comparison with national mean values from the Anthropological Atlas of Romania (Radu, Glavce, Ştirbu, 2011:52), analyze of the results shows higher dimensions for cephalic callote, height and sitting height from the series of 1972 and 1974. The students of Ecological University are closer mostly to the national mean values, excepting the height, significantly higher and also the highest in the series succession. Compared with the mean values of the students of 1929, a progressive and significant increase of height throughout eight decades is observed for the next series and a diminution trend of cephalic indices and cormic index for ecologist students. [ABSTRACT FROM AUTHOR]

Our paper represents a modest homage for the MD Th. Enăchescu, Doctor of Medicine and anthropologist, who, through his rich and complex activity, had a dominant role in the continuity and development of the Romanian anthropology after the WW2. The partial results from the (unpublished) longitudinal study regarding the body growth of the children with ages ranged from 3-18 years from two different living environments, an urban area (Bucharest) and a highland rural area (Rucăr-Bran corridor), are presented. The research was conducted between 1977 to 1985, like, many other Romanian studies, in accordance with the international auxological research. The evolution of the two most important markers, height and weight, is presented in a percentile system through a graphic modeling of the growth progression throughout the encompassed ontogenetic stages, delineating through the distance curves the percentile channels – delayed, medium and advanced growth types. The most spectacular graphic representations are those of the successive growth rates. Through annual survey, at the same date, of the same subjects, it is a longitudinal study. By losing of some subjects and adding of others throughout the project’s time, it is a mixed-longitudinal study. The final samples contain an impressive number of subjects (49,574 – a real cohort!): 19,753 boys and 19,762 girls from Bucharest, respectively 4,963 boys and 5,096 girls from the highland villages (an altitude of 700 – 1,300 meters) of the Rucăr-Bran corridor. The study shows the growth differences related to the life environment, age and gender, but its originality and importance is revealed through the methodological and applied aspect regarding the appreciation of the normality of growth and development as a mass or/and individual phenomenon. [ABSTRACT FROM AUTHOR]

The effect of consolidation on the undrained bearing capacity of both rough and smooth strip and circular surface foundations is investigated, examining the influence of the magnitude and duration of an applied preload and the initial over-consolidation ratio of the deposit. The investigation comprised small strain finite-element analysis, with the soil response represented by Modified Cam Clay. The results are distilled into dimensionless and generalised forms, from which simple trends emerge. Based on these results, a simple method for predicting the consolidated undrained bearing capacity is proposed. [ABSTRACT FROM AUTHOR]

To investigate the functional significance of mutations in Ferroportin that cause hereditary iron overload, we directly measured the iron efflux activity of the proteins expressed in Xenopus oocytes. We found that wild type and mutant Ferroportin molecules (A77D, N144H, Q248H and V162Delta) were all expressed at the plasma membrane at similar levels. All mutations caused significant reductions in (59)Fe efflux compared to wild type but all retained some residual transport activity. A77D had the strongest effect on (59)Fe efflux (remaining activity 9% of wild-type control), whereas the N144H mutation retained the highest efflux activity (42% of control). The Q248H and V162Delta mutations were intermediate between these values. Co-injection of mutant and wild-type mRNAs revealed that the A77D and N144H mutations had a dominant negative effect on the function of the WT protein. [ABSTRACT FROM AUTHOR]

Abstract Background The delta smelt (Hypomesus transpacificus) is a pelagic fish species listed as endangered under both the USA Federal and Californian State Endangered Species Acts and considered an indicator of ecosystem health in its habitat range, which is limited to the Sacramento-San Joaquin estuary in California, USA. Anthropogenic contaminants are one of multiple stressors affecting this system, and among them, current-use insecticides are of major concern. Interrogative tools are required to successfully monitor effects of contaminants on the delta smelt, and to research potential causes of population decline in this species. We have created a microarray to investigate genome-wide effects of potentially causative stressors, and applied this tool to assess effects of the pyrethroid insecticide esfenvalerate on larval delta smelt. Selected genes were further investigated as molecular biomarkers using quantitative PCR analyses. Results Exposure to esfenvalerate affected swimming behavior of larval delta smelt at concentrations as low as 0.0625 μg.L-1, and significant differences in expression were measured in genes involved in neuromuscular activity. Alterations in the expression of genes associated with immune responses, along with apoptosis, redox, osmotic stress, detoxification, and growth and development appear to have been invoked by esfenvalerate exposure. Swimming impairment correlated significantly with expression of aspartoacylase (ASPA), an enzyme involved in brain cell function and associated with numerous human diseases. Selected genes were investigated for their use as molecular biomarkers, and strong links were determined between measured downregulation in ASPA and observed behavioral responses in fish exposed to environmentally relevant pyrethroid concentrations. Conclusions The results of this study show that microarray technology is a useful approach in screening for, and generation of molecular biomarkers in endangered, non-model organisms, identifying specific genes that can be directly linked with sublethal toxicological endpoints; such as changes in expression levels of neuromuscular genes resulting in measurable swimming impairments. The developed microarrays were successfully applied on larval fish exposed to esfenvalerate, a known contaminant of the Sacramento-San Joaquin estuary, and has permitted the identification of specific biomarkers which could provide insight into the factors contributing to delta smelt population decline.

Abstract Background Iron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast Saccharomyces cerevisiae has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism. Results Using functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of CTI6, DAP1, MRS4 and YHR045W in iron metabolism. Conclusion Comparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional components. This should be taken into consideration when designing and analyzing data from these type of studies. We used this and other published data to develop a molecular interaction network of iron metabolism in yeast.