Regulation of Energy Stores and Feeding by Neuronal and Peripheral CREB Activity in Drosophila

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved

Charge Screening Effect in Metallic Carbon Nanotubes

Charge screening effect in metallic carbon nanotubes is investigated in a model including the one-dimensional long-range Coulomb interaction. It is pointed out that an external charge which is being fixed spatially is screened by internal electrons so that the resulting object becomes electrically neutral. We found that the screening length is given by about the diameter of a nanotube.Comment: 11 pages, 6 figure

Band structures of periodic carbon nanotube junctions and their symmetries analyzed by the effective mass approximation

The band structures of the periodic nanotube junctions are investigated by the effective mass theory and the tight binding model. The periodic junctions are constructed by introducing pairs of a pentagonal defect and a heptagonal defect periodically in the carbon nanotube. We treat the periodic junctions whose unit cell is composed by two kinds of metallic nanotubes with almost same radii, the ratio of which is between 0.7 and 1 . The discussed energy region is near the undoped Fermi level where the channel number is kept to two, so there are two bands. The energy bands are expressed with closed analytical forms by the effective mass theory with some assumptions, and they coincide well with the numerical results by the tight binding model. Differences between the two methods are also discussed. Origin of correspondence between the band structures and the phason pattern discussed in Phys. Rev. B {\bf 53}, 2114, is clarified. The width of the gap and the band are in inverse proportion to the length of the unit cell, which is the sum of the lengths measured along the tube axis in each tube part and along 'radial' direction in the junction part. The degeneracy and repulsion between the two bands are determined only from symmetries.Comment: RevTeX, gif fil

Electronic states and quantum transport in double-wall carbon nanotubes

Electronic states and transport properties of double-wall carbon nanotubes without impurities are studied in a systematic manner. It is revealed that scattering in the bulk is negligible and the number of channels determines the average conductance. In the case of general incommensurate tubes, separation of degenerated energy levels due to intertube transfer is suppressed in the energy region higher than the Fermi energy but not in the energy region lower than that. Accordingly, in the former case, there are few effects of intertube transfer on the conductance, while in the latter case, separation of degenerated energy levels leads to large reduction of the conductance. It is also found that in some cases antiresonance with edge states in inner tubes causes an anomalous conductance quantization, $G=e^2/\pi\hbar$, near the Fermi energy.Comment: 24 pages, 13 figures, to be published in Physical Review

Optical response of finite-length carbon nanotubes

Optical response of finite-length metallic carbon nanotubes is calculated including effects of induced edge charges in a self-consistent manner. The results show that the main resonance corresponding to excitation of the fundamental plasmon mode with wave vector $\pi/l$ with $l$ being the tube length is quite robust and unaffected. This arises because the strong electric field associated with edge charges is screened and decays rapidly inside the nanotube. For higher-frequency resonances, the field starts to be mixed and tends to shift resonances to higher frequencies.Comment: 10 pages, 9 figures, to be published in J. Phys. Soc. Jp

Vacuum structure of Toroidal Carbon Nanotubes

Low energy excitations in carbon nanotubes can be described by an effective field theory of two components spinor. It is pointed out that the chiral anomaly in 1+1 dimensions should be observed in a metallic toroidal carbon nanotube on a planar geometry with varying magnetic field. We propose an experimental setup for studying this quantum effect. We also analyze the vacuum structure of the metallic toroidal carbon nanotube including the Coulomb interactions and discuss some effects of external charges on the vacuum.Comment: 10 pages, 11 figure

Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

Aharonov-Bohm spectral features and coherence lengths in carbon nanotubes

The electronic properties of carbon nanotubes are investigated in the presence of disorder and a magnetic field parallel or perpendicular to the nanotube axis. In the parallel field geometry, the $\phi_{0}(=hc/e)$-periodic metal-insulator transition (MIT) induced in metallic or semiconducting nanotubes is shown to be related to a chirality-dependent shifting of the energy of the van Hove singularities (VHSs). The effect of disorder on this magnetic field-related mechanism is considered with a discussion of mean free paths, localization lengths and magnetic dephasing rate in the context of recent experiments.Comment: 22 pages, 6 Postscript figures. submitted to Phys. Rev.

Aβ42 Mutants with Different Aggregation Profiles Induce Distinct Pathologies in Drosophila

Aggregation of the amyloid-β-42 (Aβ42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Aβ aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Aβ can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Aβ42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Aβ42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Aβ42Arc) and an artificial mutation (Aβ42art) that is known to suppress aggregation and toxicity of Aβ42 in vitro. In the Drosophila brain, Aβ42Arc formed more oligomers and deposits than did wild type Aβ42, while Aβ42art formed fewer oligomers and deposits. The severity of locomotor dysfunction and premature death positively correlated with the aggregation tendencies of Aβ peptides. Surprisingly, however, Aβ42art caused earlier onset of memory defects than Aβ42. More remarkably, each Aβ induced qualitatively different pathologies. Aβ42Arc caused greater neuron loss than did Aβ42, while Aβ42art flies showed the strongest neurite degeneration. This pattern of degeneration coincides with the distribution of Thioflavin S-stained Aβ aggregates: Aβ42Arc formed large deposits in the cell body, Aβ42art accumulated preferentially in the neurites, while Aβ42 accumulated in both locations. Our results demonstrate that manipulation of the aggregation propensity of Aβ42 does not simply change the level of toxicity, but can also result in qualitative shifts in the pathology induced in vivo