N2-(p-n-Octylphenyl)dGTP: Synthesis and Inhibitory Activity Against DNA Polymerases

Abstract

N²-(p-n-Octylphenyl)-2′-deoxyguanosine 5′-triphosphate (OctPdGTP)has been synthesized chemically. OctPdGTP inhibited DNA polymerases (pol) α, δ and ε from calf thymus, with moderate selectivity for pol α. Mechanistic studies on pol α and bacteriophage T4 DNA polymerase revealed competitive and mixed kinetics of OctPdGTP with respect to the substrate dGTP when the enzymes were assayed on activated DNA and oligo dT:poly dA, respectively.

     

Sex-related,growth–climate association of Araucaria angustifolia in the neotropical ombrophilous woodlands of Argentina

Araucaria angustifolia is a dioecious dominant tree in araucaria forests in Brazil and Argentina, South America. The species is nowadays critically endangered by deforestation and global climate change. The goal of this study was to analyse the dynamics of radial growth in this species and its association with climatic variables, according to the sex, at its western range boundary in Argentina. Standard dendrochronological techniques were applied on stem disks from female and male trees. Xylem anatomical anomalies made the tree-ring dating process difficult. Female and male trees showed growth patterns that changed over time, not being significant in the 1950–1990 period and highly significant from the 1990s onwards (p < 0.1) when female trees had a higher growth rate. Female and male trees showed a different association with climatic variables. No significant effect of temperature and precipitation was identified on female trees. For male trees, rainfall had a positive effect in August, before the growing season, and a negative effect at the end of the growing season (March). Temperature had a negative effect on male trees, before and during the growing season (February and January, respectively). No effect of SOI was detected on both sexes. Results emphasised the usefulness of A. angustifolia for dendrochronological studies and the value of dioecious species for the study of sex-related growth–climate association.     

ProNGF\NGF imbalance triggers learning and memory deficits,neurodegeneration and spontaneous epileptic-like discharges in transgenic mice

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer''s disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aβ-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aβ oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.     

Comparison of rat hepatocyte and differentiated hepatoma cell line cultures as bio indicators of CYP 1A1 inducers in urban air

Cytochrome P450 1A1 CYP1A1 enzymatic activity was evaluated in cultured liver cells, and taken as a biological indicator of the presence of inducers of this isoform in urban airborne particulate matter fraction samples. It is known that CYP1A1 inducers can play an important role in the risk of mutagenesis and carcinogenesis by environmental pollution. A romatic polycyclic hydrocarbons PAH from urban air were collected in the city of Genoa Italy at two sites on two different days of the year. The objective of the study was to compare the inducibility of cultured rat hepatocytes with that of MH1C1 and FaO rat hepatoma cell lines after exposure to a PAH mixture and to a standard compound, such as benzo b fluoranthene B b F. Cytotoxic effects of the tested concentrations were evaluated by means of 3 4,5, dimenthylthyazol 2 yl 2,5 diphenyltetrazolium bromide MTT and lactate dehydrogenase release LDH tests, the potency of inducers by ethoxyresorufin O deethylase EROD assay. The results were in agreement in the three cellular systems: after exposure to the PAH mixture, an induction at low concentrations was observed; whereas no induction, but rather a decrease in activity was shown at higher concentrations; instead, the exposure to pure B b F showed a dose-response relationship in all cells, even at the highest doses. Such a difference between the toxicity of the complex mixture and that of the pure compound could be ascribed to the presence of drug metabolism inhibitors in the mixture, or to interactions between the original components and their metabolites. The finding that the cell lines responded to the CYP1A1 induction in a very efficient way gives further proof of the applicability of this system to environmental biomonitoring.     

A novel comparative research platform designed to determine the functional significance of tree species diversity in European forests

One of the current advances in functional biodiversity research is the move away from short-lived test systems towards the exploration of diversity-ecosystem functioning relationships in structurally more complex ecosystems. In forests, assumptions about the functional significance of tree species diversity have only recently produced a new generation of research on ecosystem processes and services. Novel experimental designs have now replaced traditional forestry trials, but these comparatively young experimental plots suffer from specific difficulties that are mainly related to the tree size and longevity. Tree species diversity experiments therefore need to be complemented with comparative observational studies in existing forests. Here we present the design and implementation of a new network of forest plots along tree species diversity gradients in six major European forest types: the FunDivEUROPE Exploratory Platform. Based on a review of the deficiencies of existing observational approaches and of unresolved research questions and hypotheses, we discuss the fundamental criteria that shaped the design of our platform. Key features include the extent of the species diversity gradient with mixtures up to five species, strict avoidance of a dilution gradient, special attention to community evenness and minimal covariation with other environmental factors. The new European research platform permits the most comprehensive assessment of tree species diversity effects on forest ecosystem functioning to date since it offers a common set of research plots to groups of researchers from very different disciplines and uses the same methodological approach in contrasting forest types along an extensive environmental gradient.     

Differences in neuromuscular control between impact and no impact roundhouse kick in athletes of different skill levels

This study aimed at investigating two aspects of neuromuscular control around the hip and knee joint while executing the roundhouse kick (RK) using two techniques: Impact RK (IRK) at trunk level and No-Impact RK at face level (NIRK). The influence of technical skill level was also investigated by comparing two groups: elite Karateka and Amateurs. Surface electromyographic (sEMG) signals have been recorded from the Vastus Lateralis (VL), Biceps Femoris (BF), Rectus Femoris (RF), Gluteus Maximum (GM) and Gastrocnemious (GA) muscles of the kicking leg in six Karateka and six Amateurs performing the RKs. Hip and knee kinematics were also assessed. EMG data were rectified, filtered and normalized to the maximal value obtained for each muscle over all trials; co-activation (CI) indexes of antagonist vs. overall (agonist and antagonist) activity were computed for hip and knee flexion and extension. Muscle Fiber Conduction Velocity (CV) obtained from VL and BF muscles was assessed as well. The effect of group and kick on angular velocity, CIs, and CVs was tested through a two-way ANOVA (p < 0.05). An effect of group was showed in both kicks. Karateka presented higher knee and hip angular velocity; higher BF-CV (IRK: 5.1 ± 1.0 vs. 3.5 ± 0.5 m/s; NIRK: 5.7 ± 1.3 vs. 4.1 ± 0.5 m/s), higher CIs for hip movements and knee flexion and lower CI for knee extension. The results obtained suggest the presence of a skill-dependent activation strategy in the execution of the two kicks. CV results are suggestive of an improved ability of elite Karateka to recruit fast MUs as a part of training induced neuromuscular adaptation.     

Mitochondria,oxidative stress and aging

In the eighties, Miquel and Fleming suggested that mitochondria play a key role in cellular aging. Mitochondria, and specially mitochondrial DNA (mtDNA), are major targets of free radical attack. At present, it is well established that mitochondrial deficits accumulate upon aging due to oxidative damage. Thus, oxidative lesions to mtDNA accumulate with age in human and rodent tissues. Furthermore, levels of oxidative damage to mtDNA are several times higher than those of nuclear DNA. Mitochondrial size increases whereas mitochondrial membrane potential decreases with age in brain and liver.

Recently, we have shown that treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and oxidation of mitochondrial glutathione. Moreover, the extract EGb 761 also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. Thus, mitochondrial aging may be prevented by antioxidants. Furthermore, late onset administration of certain antioxidants is also able to prevent the impairment in physiological performance, particularly motor co-ordination, that occurs upon aging.     

Eve's sons

Abstract

The aim of this article is to use the episode of the baby allegedly cloned by the Raelians and born on the day after Christmas 2002 in order to analyse what is threatened by the prospect of cloning as a reproductive method, and why it is a matter of such importance as to provoke immediate and general condemnation. The announcement made by the Raelians provoked public debate in the media. Therefore, analysis of the articles published in the main Italian newspapers during that period allows exploration of the hypothesis that the Raelians' attempt of cloning was generally interpreted as a threat against the basis of our conception of human identity, not only at the individual level—which defines each of us as a balance between difference and continuity—but also at the social level, where human identity is the result of a classification system in which human beings are identified in contrast to other living beings. For these reasons, the case of the Raelians is of particular interest because it strains the reproduction/identity nexus in an extreme way which highlights what otherwise may lie buried beneath a thick layer of taken-for-granted beliefs.