Is There a Causal Association between Genotoxicity and the Imposex Effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways

Enhanced fluctuations of the tunneling density of states near bottoms of Landau bands measured by a local spectrometer

We have found that the local density of states fluctuations (LDOSF) in a disordered metal, detected using an impurity in the barrier as a spectrometer, undergo enhanced (with respect to SdH and dHvA effects) oscillations in strong magnetic fields, omega _c\tau > 1. We attribute this to the dominant role of the states near bottoms of Landau bands which give the major contribution to the LDOSF and are most strongly affected by disorder. We also demonstrate that in intermediate fields the LDOSF increase with B in accordance with the results obtained in the diffusion approximation.Comment: 4 pages, 4 figure

Book Review Roundtable: Alexander Cooley’s Great Games, Local Rules: The New Great Power Contest in Central Asia

In this book review roundtable, seven experts discuss Alexander Cooley’s Great Games, Local Rules: The New Great Power Contest in Central Asia, followed by a response essay from the author

Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications

Dynamical phenomena in Fibonacci Semiconductor Superlattices

We present a detailed study of the dynamics of electronic wavepackets in Fibonacci semiconductor superlattices, both in flat band conditions and subject to homogeneous electric fields perpendicular to the layers. Coherent propagation of electrons is described by means of a scalar Hamiltonian using the effective-mass approximation. We have found that an initial Gaussian wavepacket is filtered selectively when passing through the superlattice. This means that only those components of the wavepacket whose wavenumber belong to allowed subminibands of the fractal-like energy spectrum can propagate over the entire superlattice. The Fourier pattern of the transmitted part of the wavepacket presents clear evidences of fractality reproducing those of the underlying energy spectrum. This phenomenon persists even in the presence of unintentional disorder due to growth imperfections. Finally, we have demonstrated that periodic coherent-field induced oscillations (Bloch oscillations), which we are able to observe in our simulations of periodic superlattices, are replaced in Fibonacci superlattices by more complex oscillations displaying quasiperiodic signatures, thus sheding more light onto the very peculiar nature of the electronic states in these systems.Comment: 7 pagex, RevTex, 5 Postscript figures. Physical Review B (in press

Energy spectra of quasiperiodic systems via information entropy

We study the relationship between the electronic spectrum structure and the configurational order of one-dimensional quasiperiodic systems. We take the Fibonacci case as an specific example, but the ideas outlined here may be useful to accurately describe the energy spectra of general quasiperiodic systems of technological interest. Our main result concerns the {\em minimization} of the information entropy as a characteristic feature associated to quasiperiodic arrangements. This feature is shown to be related to the ability of quasiperiodic systems to encode more information, in the Shannon sense, than periodic ones. In the conclusion we comment on interesting implications of these results on further developments on the issue of quasiperiodic order.Comment: REVTeX 3.0, 8 pages, 3 figures available on request from FD-A ([email protected]), Phys Rev E submitted, MA/UC3M/02/9

Fermi-Edge Singularities in AlxGa1-xAs Quantum Wells : Extrinsic Versus Many-Body Scattering Processes

A Fano resonance mechanism is evidenced to control the formation of optical Fermi-edge singularities in multi-subband systems such as remotely doped AlxGa1-xAs heterostructures. Using Fano parameters, we probe the physical nature of the interaction between Fermi-sea electrons and empty conduction subbands. We show that processes of extrinsic origin like alloy-disorder prevail easily at 2D over multiple diffusions from charged valence holes expected by many-body scenarios.Comment: 4 pages, 3 figures, accepted for publication in Physical Review Letter