Internal and external effects on cognition: Evidence from memory training in very preterm-born children and cognition in patients with carotid artery stenosis before and after treatment

The present synopsis aims to integrate one study about memory training in very preterm-born children and two studies about cognition in patients with carotid artery stenosis before and after treatments. Preterm-born children are at increased risk of cognitive deficits and behavioural problems compared with peers born at term. This thesis determined whether memory training would improve cognitive functions in school-age very preterm-born children. Memory strategy training produced significant improvements in trained and non-trained cognitive functions; a core working memory training revealed significant effects on short-term memory and working memory tasks. Six months after training, children in both training groups showed better working memory performance than children in the waiting control group. This is evidence that memory training – an external influence on cognition – induces plastic changes in very preterm-born children. Patients with carotid artery stenosis are known to be at increased risk of cognitive impairment. We showed that patients with symptomatic or asymptomatic carotid artery stenosis were at higher risk for cognitive deficits than expected in a normative sample. This thesis seeks to link cognitive plasticity to internal factors like carotid stenosis. An external factor, which influences blood flow to the brain is the nature of the carotid artery stenosis treatment. Research on the effects of carotid artery stenosis treatment on cognition has produced inconsistent results. We found significant improvement in frontal lobe functions, visual memory and motor speed one year after treatment independent of the treatment type (best medical treatment, carotid artery stenting, carotid artery endarterectomy); providing evidence for ‘treatment-induced’ cognitive plasticity. Baseline performance was negatively associated with improvement in various cognitive functions after training in very preterm-born children and after treatment in patients with carotid artery stenosis. The present synopsis aims to integrate these findings into the current and relevant literature, and discuss consequences as well as methodological considerations resulting from the studies constituting the thesis at hand.

SYNTHETIC PROBES FOR STUDYING TUFTSIN-RECEPTOR INTERACTIONS ON HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Tuftsin is an immunopotentiating tetrapeptide of the sequence L-Thr-L-Lys-L-Pro-L-Arg with anti-microbial and anti-tumor enhancing capabilities. These enhancing functions are manifested through the host's granulocytes and monocytes. In delineating tuftsin's mechanism of action, both radiolabeled and fluorescent probes were synthesized. The radiolabeled probe of tuftsin, L-proly-3,4-('3)H(N) -tuftsin, was obtained through the synthesis and subsequent catalytic hydrogenation of L-3,4-dehydroprolyl ('3)-tuftsin using tritium gas. This procedure yielded a probe with a specific activity of 44.9 Ci/mmole. This radiolabeled probe of tuftsin was used in competitive inhibition studies with tuftsin, the tuftsin analogues Lys-Pro-Arg, Thr-Lys-Pro-Arg(NO(,2)) and (DELTA)('3)-pro('3) -tuftsin as well as with the chemotactic peptide f-Met-Leu-Phe. From the competitive binding curves, the K(,D) for tuftsin was estimated to be 80 nM, a value that approaches the concentration of tuftsin that evokes a half maximal biological response. The approximate Ki's for the tuftsin analogues (33 nM) approached that of tuftsin itself (40 nM). On the other hand, approximately a two log difference in the Ki was seen with the chemotactic tripeptide, indicating that tuftsin may indeed be acting through the chemotactic peptide receptor. This conclusion is further strengthened by studies using an N-terminal derivitized mono-fluoresceinated tuftsin probe and image intensification microscopy. These studies showed that like the chemotactic peptide, tuftsin initially binds to diffusely distributed receptors on the surface of human granulocytes. The tuftsin-receptor complexes then rapidly redistribute to form patches (5 min @ 37(DEGREES)C) which are then internalized. Whether redistribution and internalization of tuftsin-receptor complexes is crucial in effecting a biological response, or simply an intermediary point leading ultimately to degradation, is still not clear. This process, however, may provide the target cell with an early time point in modulating the biological effects of tuftsin through down-regulation of cell surface receptor sites. ^

Labeling in the Classroom: Teacher Expectations and their Effects on Students' Academic Potential

The transition to high school can be challenging for some adolescents, resulting in drops of academic functioning (Barber & Olsen, 2004; Smith, 2006). While changes in academic demands and the disparity between adolescent needs and the environmental characteristics of high school have both been cited as possible contributors to this decrease in academic and personal functioning (Barber & Olsen, 2004), it is possible that teachers may play an even larger role in undermining these students’ functioning, specifically through labeling. Although labeling, and how it can lead to self-fulfilling prophesies, is a concept that has been thoroughly researched and applied to the field of criminology and deviant behavior, it is the goal of this current study to investigate if labeling also occurs in the classroom setting and how such labels ultimately effect the academic potential of high school students.

Esx1 dosage impacts reproductive fitness: Effects on viability and fertility

Numerous genes expressed in placenta or testis localize to the X-chromosome. Both tissues undergo specialized X-chromosome inactivation (imprinted paternal inactivation in placenta and MSCI in testicular germ cells). When the X-chromosome is duplicated or improperly inactivated, defects in placentation, growth and spermatogenesis are noted, suggesting tight control of X-chromosome gene dosage is important for reproduction. ^ Esx1 is a mouse homeobox gene on the X-chromosome with expression limited to extraembryonic tissues and testicular germ cells. Here, we examine the effects of increased and decreased Esx1 dosage on placental and testicular development, the role of genetic background on Esx1 function and characterize the human orthologue of Esx1. ^ Previously, by targeted deletion, Esx1 was shown to be an X-chromosome imprinted regulator of placental development and fetal growth. We show C57Bl6-congenic Esx1 mutants display a more severe phenotype with decreased viability and that the 129 genetic background contains dominant modifier genes that enhance Esx1 mutant survival. ^ Varying Esx1 dosage impacts testicular germ cell development. Esx1 hemizygous null mice are fertile, but we show their testes are two-thirds normal size. To examine the effect of increased Esx1 dosage, Esx1 BAC transgenic mice were generated. Increased Esx1 dosage results in dramatic deficits in testicular germ cell development, leading to sterility and testes one-fourth normal size. We show germ cell loss occurs through apoptosis, begins between postnatal day 6 and 10, and that no spermatocytes complete meiosis. Interestingly, increased Esx1 dosage in testes mimics germ cell loss seen in Klinefelter's (XXY) mice and humans and may represent a molecular mechanism for the infertility characteristic of this syndrome. ^ Esx1 dosage impacts reproductive fitness when maternally transmitted. Three transgenic founder females were unable to transmit the transgene to live offspring, but did produce transgenic pups at earlier stages. Additionally, one line of Esx1 BAC transgenic mice demonstrated decreased embryo size and fitness when the transgene is inherited compared to wild type littermates. ^ It is possible that Esx1 plays a role in human disorders of pregnancy, growth and spermatogenesis. Therefore, we cloned and characterized ESX1L (human Esx1), and show it is expressed in human testis and placenta. ^

Environmental influences on self-reported leisure-time physical activity in the Austin/Travis County STEPS survey 2005--2009

This study was an examination of environmental and social correlates of physical inactivity in a socio-economically disadvantaged community. This study was a secondary analysis of data collected by the Austin/Travis County Department of Health and Human Services. The study included an analysis of perceived environmental influences (e.g. access to physical support features like sidewalks and streetlights). This study also investigated several features of the social environment (e.g. perceived neighborhood crime and social influence). Participants’ beliefs and attitudes about the neighborhood were investigated. Results included estimates of the association between neighborhood factors and physical inactivity controlling for age, gender and education. This study found significant associations for social and environmental variables with physical inactivity. The goal of this work was to identify factors that contribute to inactivity and address a number of environmental and neighborhood risk factors that contribute to sedentary behaviors in a population of relative social and economic disadvantage.^

A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

Impact of environmental regulations on lead concentrations in Texas ambient air and water: 1970--1990

In the last two decades, the significance of lead has been addressed in a number of environmental regulations at the national and state levels. This project investigated the environmental regulations (Clean Air Act and Amendments, 1970-1990 and Clean Water Act of 1977) and their cumulative effects on lead in ambient air and water in the state of Texas. For this purpose, historical records from the Texas Water Development Board, Texas Natural Resources Conservation Commission, and the United States Geological Survey have been assembled and analyzed for temporal and spatial trends. These trends might correspond to the phase out of lead in gasoline and other regulations.^ This study concluded that there is a significant correlation (p $\leq$.001) between environmental regulations of lead in gasoline and the concentration of lead in ambient air. Lead concentrations in ambient air have been reduced by over 90 percent in the past twenty years. An overall significant difference (p $\leq$.001) was found in mean (94, 15 respectively) lead concentrations in surface water between two time periods, one at the beginning of the twenty year period and one at the end of the study period. There has been an overall reduction of lead concentrations in surface water in Texas of approximately 84 percent. However, this reduction cannot be statistically associated with any one regulation. Groundwater data could not be analyzed for lead concentrations because of limitations of reporting data as "less than". Approximately two percent of the groundwater data was analyzed by Oneway ANOVA and no significant difference was found between the means (18, 19 respectively) of two time periods, 1977-1979 and 1988-1990. This data is consistent with the regulations having a contributory affect on declining concentrations, but other factors cannot be ruled out as having added to these declines. This study can also serve as a starting point for a more in-depth study of environmental regulations and their impact on the environment. ^

RUNOFF FROM COAL PILES: EFFECTS ON THE ENVIRONMENT AND THE PUBLIC'S HEALTH

The use of coal for fuel in place of oil and natural gas has been increasing in the United States. Typically, users store their reserves of coal outdoors in large piles and rainfall on the coal creates runoffs which may contain materials hazardous to the environment and the public's health. To study this hazard, rainfall on model coal piles was simulated, using deionized water and four coals of varying sulfur content. The simulated surface runoffs were collected during 9 rainfall simulations spaced 15 days apart. The runoffs were analyzed for 13 standard water quality parameters, extracted with organic solvents and then analyzed with capillary column GC/MS, and the extracts were tested for mutagenicity with the Ames Salmonella microsomal assay and for clastogenicity with Chinese hamster ovary cells.^ The runoffs from the high-sulfur coals and the lignite exhibited extremes of pH (acidity), specific conductance, chemical oxygen demand, and total suspended solids; the low-sulfur coal runoffs did not exhibit these extremes. Without treatment, effluents from these high-sulfur coals and lignite would not comply with federal water quality guidelines.^ Most extracts of the simulated surface runoffs contained at least 10 organic compounds including polycyclic aromatic hydrocarbons, their methyl and ethyl homologs, olefins, paraffins, and some terpenes. The concentrations of these compounds were generally less than 50 (mu)g/l in most extracts.^ Some of the extracts were weakly mutagenic and affected both a DNA-repair proficient and deficient Salmonella strain. The addition of S9 decreased the effect significantly. Extracts of runoffs from the low-sulfur coal were not mutagenic.^ All extracts were clastogenic. Extracts of runoffs from the high-sulfur coals were both clastogenic and cytotoxic; those from the low-sulfur coal and the lignite were less clastogenic and not cytotoxic. Clastogenicity occurred with and without S9 activation. Chromosomal lesions included gaps, breaks and exchanges. These data suggest a relationship between the sulfur content of a coal, its mutagenicity and also its clastogenicity.^ The runoffs from actual coal piles should be investigated for possible genotoxic effects in view of the data presented in this study.^

Ascorbic acid effects on the immune system and type -1 /type -2 cytokine balance in humans

Vitamin C (ascorbic acid--AA) can have a substantial impact on human health by reducing the incidence and/or severity of coryza. Studies also suggest it has immunomodulatory functions in humans. Immune function is controlled by cytokines, such as type-1 cytokines (IFNγ) that promote antiviral immunity and type-2 cytokines (IL-4, IL-10) that promote humoral immunity. Knowing the mechanisms responsible for both antiviral immunity and type-1/type-2 cytokine balance, we sought to identify AA-induced alterations of human peripheral blood mononuclear cells (PBMC) in vivo and in vitro . We hypothesized that AA modulates the immune system, altering both number and function of PBMC. We first described the effect of 14 days of oral (1 gram) AA in healthy subjects. AA increased circulating natural killer (NK) cells, CD25+ and HLA-DR+ T cells, and PMA/ionomycin-stimulated intracellular IFNγ. We subsequently developed models for in vitro use. We determined that AA was toxic in vitro to T cells when used at doses found intracellularly but doses found in plasma from individuals taking 1gm/day AA were nontoxic. The model that most fully reproduced our in vivo intracellular cytokine findings used dehydroascorbic acid and buffers to deliver AA intracellularly. This model generated the largest increase in IFNγ at physiologic plasma concentrations. Previous studies demonstrate that chronic psychological stress is associated with a type-2 cytokine response. We hypothesized that vitamin C could prevent the type-2 cytokine shift associated with stress. In a study of medical students taking 1 g AA or placebo, a significant increase in IFNγ was seen intracellularly in CD4+ and CD8+ cells and in tetanus-stimulated cultures in the AA group only. We also observed increases in IFNγ/IL-4 and IFNγ/IL-10 ratios with AA supplementation, indicating a type-1 shift. Furthermore, we noted increased numbers of NK cells and activated T cells in the peripheral blood in the AA treated group only. Lastly, we investigated the role of the CD40L/CD40 and CD28/B7 costimulatory pathway in these cytokine alterations. AA did not have any effect on either pathway studied. Thus costimulatory pathways are not contributing to AA induced modulation of the type-1/type-2 immune balance. ^

Biochar and compost effects on mobility of Cu and other soil parameters and plant growth

A pot experiment was conducted to determine the effects of three biochars and compost on plant growth and the immobilisation of Cu in a contaminated soil obtained from a former wood preservation site in the Gironde County Saint Médard d'Eyrans, France (N 44° 43.353, W 0° 30.938). To assess Cu mobility, amended soils were analysed using CaCl**2 leaching tests pre- and post-incubation, and post-growth. Amended and unamended soils were planted with sunflower, and the resulting plant material was assessed for yield (mass and height) and Cu concentration. All amendments significantly reduced leachable Cu compared to the unamended soil, however, the greatest reductions in leachable Cu were associated with the higher biochar application rate. The greatest improvements in plant yields were obtained with the higher application rate of biochar in combination with compost. pH, DOC, EH were measured in soils to help explain the leaching and plant growth trends. Soil pore water was collected during plant growth and analysed for metal concentration, pH and EH. Prior to treatment, background analyses were carried out on the soil and individual amendments (including PAH + metal concentrations measured by gas chromatography mass spectrometry and ICP-AES respectively).

Temperature and photoperiod effects on sex determination in Leuresthes tenuis (fish)

In some gonochoristic species, sex is influenced not only by genotype at conception but also by the environment that offspring experience during early ontogeny (termed environmental sex determination or ESD). ESD is thought to be adaptive when seasonal variations in environmental conditions provide a sex-specific fitness advantage. In vertebrates, temperature is the most common determinant of sex, and seasonal variation in temperature serves as a temporal cue of environmental quality such as length of the growing season. Some environments, however, lack strong seasonal temperature fluctuations and other cues, particularly photoperiod, may provide a more reliable indicator of the environment offspring enter. We tested this hypothesis by rearing the offspring of the California grunion (Leuresthes tenuis, Ayres), which experiences low seasonal temperature variation in nature, under common garden conditions at three temperature and two photoperiod treatments. Our experiments revealed that both temperature and photoperiod significantly affected sex ratios in L. tenuis. More females were produced at cooler temperatures and longer day lengths, which is consistent with female biased sex ratios early in the breeding season, and likely adaptive through increased female size and fecundity. To our knowledge, this is the first documented case of photoperiod-dependent sex determination in a gonochoristic vertebrate.

Small Changes in pH Have Direct Effects on Marine Bacterial Community Composition: A Microcosm Approach

As the atmospheric CO2 concentration rises, more CO2 will dissolve in the oceans, leading to a reduction in pH. Effects of ocean acidification on bacterial communities have mainly been studied in biologically complex systems, in which indirect effects, mediated through food web interactions, come into play. These approaches come close to nature but suffer from low replication and neglect seasonality. To comprehensively investigate direct pH effects, we conducted highly-replicated laboratory acidification experiments with the natural bacterial community from Helgoland Roads (North Sea). Seasonal variability was accounted for by repeating the experiment four times (spring, summer, autumn, winter). Three dilution approaches were used to select for different ecological strategies, i.e. fast-growing or low-nutrient adapted bacteria. The pH levels investigated were in situ seawater pH (8.15-8.22), pH 7.82 and pH 7.67, representing the present-day situation and two acidification scenarios projected for the North Sea for the year 2100. In all seasons, both automated ribosomal intergenic spacer analysis and 16S ribosomal amplicon pyrosequencing revealed pH-dependent community shifts for two of the dilution approaches. Bacteria susceptible to changes in pH were different members of Gammaproteobacteria, Flavobacteriaceae, Rhodobacteraceae, Campylobacteraceae and further less abundant groups. Their specific response to reduced pH was often context-dependent. Bacterial abundance was not influenced by pH. Our findings suggest that already moderate changes in pH have the potential to cause compositional shifts, depending on the community assembly and environmental factors. By identifying pH-susceptible groups, this study provides insights for more directed, in-depth community analyses in large-scale and long-term experiments.

The effect of EU environmental regulation on international trade : restriction of hazardous substance as a trade barrier

In 2003 the Restriction of Hazardous Substances (RoHS) was established in the EU, which limited the trade of machinery, electrical and electronic equipment that have at least one of the substances considered hazardous under RoHS directive. Since countries trading with the EU must comply with this new regulation, it is expected a decrease in value of imports to the EU. In this paper, it is followed the procedures used in Heckman (1979), as well as the extended procedure suggested by Helpman, Melitz, and Rubinstein (2008) to ascertain the effects on the persistence of trade and values of trade.

Environmental assay on the effect of poultry manure application on soil organisms in agroecosystems

This paper reports the effects produced on the organisms of the soil (plants, invertebrates and microorganisms), after the application of two types of poultry manure (sawdust and straw bed) on an agricultural land. The test was made using a terrestrial microcosm, Multi-Species Soil System (MS3) developed in INIA. There was no difference in the germination for any of the three species of plants considered in the study. The biomass was increased in the wheat (Triticum aestivum) coming from ground treated with both kinds of poultry manure. Oilseed rape (Brasica rapa) was not affected and regarding vetch (Vicia sativa) only straw poultry manure showed significant difference. For length only Vicia sativa was affected showing a reduction when straw was exposed to poultry manure. When the effect on invertebrates was studied, we observed a reduction in the number of worms during the test, especially from the ground control (13.7%), higher than in the ground with sawdust poultry manure (6.7%), whereas in the ground with straw poultry manure, there was no reduction. The biomass was affected and at the end of the test it was observed that while the reduction of worms in the ground control was about 48%, the number of those that were in the ground with sawdust poultry manure or straw poultry manure decreased by 41% and 22% respectively. Finally, the effects on microorganisms showed that the enzymatic activities: dehydrogenase (DH) and phosphatase and basal respiration rate increased at the beginning of the test, and the differences were statistically significant compared with the values of the control group. During the test, all these parameters decreased (except DH activities) but they were always higher than in the ground control. This is why it is possible to deduce that the contribution of poultry manure caused an improvement in the conditions of fertilization and also for the soil.

Meta-analysis of strategies to control nitrate leaching in irrigated agricultural systems and their effects on crop yield.

Nitrate leaching (NL) is an important N loss process in irrigated agriculture that imposes a cost on the farmer and the environment. A meta-analysis of published experimental results from agricultural irrigated systems was conducted to identify those strategies that have proven effective at reducing NL and to quantify the scale of reduction that can be achieved. Forty-four scientific articles were identified which investigated four main strategies (water and fertilizer management, use of cover crops and fertilizer technology) creating a database with 279 observations on NL and 166 on crop yield. Management practices that adjust water application to crop needs reduced NL by a mean of 80% without a reduction in crop yield. Improved fertilizer management reduced NL by 40%, and the best relationship between yield and NL was obtained when applying the recommended fertilizer rate. Replacing a fallow with a non-legume cover crop reduced NL by 50% while using a legume did not have any effect on NL. Improved fertilizer technology also decreased NL but was the least effective of the selected strategies. The risk of nitrate leaching from irrigated systems is high, but optimum management practices may mitigate this risk and maintain crop yields while enhancing environmental sustainability.