192 research outputs found
Chalcogen Height Dependence of Magnetism and Fermiology in FeTe_xSe_{1-x}
FeTexSe1-x (x=0, 0.25, 0.50, 0.75 and 1) system has been studied using
density functional theory. Our results show that for FeSe, LDA seems better
approximation in terms of magnitude of magnetic energy whereas GGA
overestimates it largely. On the other hand for FeTe, GGA is better
approximation that gives experimentally observed magnetic state. It has been
shown that the height of chalcogen atoms above Fe layers has significant effect
on band structure, electronic density of states (DOS) at Fermi level N(EF) and
Fermi surfaces. For FeSe the value of N(EF) is small so as to satisfy Stoner
criteria for ferromagnetism, (I\timesN(EF)\geq1) whereas for FeTe, since the
value of N(EF) is large, the same is close to be satisfied. Force minimization
done for FeTexSe1-x using supercell approach shows that in disordered system Se
and Te do not share same site and have two distinct z coordinates. This has
small effect on magnetic energy but no significant difference in band structure
and DOS near EF when calculated using either relaxed or average value of z for
chalcogen atoms. Thus substitution of Se at Te site decreases average value of
chalcogen height above Fe layers which in turn affect the magnetism and
Fermiology in the system. By using coherent-potential approximation for
disordered system we found that height of chalcogen atoms above Fe layer rather
than chalcogen species or disorder in the anion planes, affect magnetism and
shape of Fermi surfaces (FS), thus significantly altering nesting conditions,
which govern antiferromagnetic spin fluctuations in the system.Comment: 24 pages Text+Figs: comments/suggestions welcome
([email protected]
Unexplored photoluminescence from bulk and mechanically exfoliated few layers of Bi2Te3
We report the exotic photoluminescence (PL) behaviour of 3D topological
insulator Bi2Te3 single crystals grown by customized self-flux method and
mechanically exfoliated few layers (18 plus minus 2 nm)/thin flakes obtained by
standard scotch tape method from as grown Bi2Te3 crystals.The experimental PL
studies on bulk single crystal and mechanically exfoliated few layers of Bi2Te3
evidenced a broad red emission in the visible region. These findings are in
good agreement with our theoretical results obtained using the ab initio
density functional theory framework.Comment: Main MS (17 Pages text including 4 Figs): Suppl. info. (4 pages);
Accepted Scientific Report
Level Density of a Bose Gas and Extreme Value Statistics
We establish a connection between the level density of a gas of
non-interacting bosons and the theory of extreme value statistics. Depending on
the exponent that characterizes the growth of the underlying single-particle
spectrum, we show that at a given excitation energy the limiting distribution
function for the number of excited particles follows the three universal
distribution laws of extreme value statistics, namely Gumbel, Weibull and
Fr\'echet. Implications of this result, as well as general properties of the
level density at different energies, are discussed.Comment: 4 pages, no figure
Modulation of Heat Shock Transcription Factor 1 as a Therapeutic Target for Small Molecule Intervention in Neurodegenerative Disease
A yeast-based small molecule screen identifies a novel activator of human HSF1 and protein chaperone expression and which appears to alleviate the toxicity of protein misfolding diseases
Optical second harmonic generation in Yttrium Aluminum Borate single crystals (theoretical simulation and experiment)
Experimental measurements of the second order susceptibilities for the second
harmonic generation are reported for YAl3(BO3)4 (YAB) single crystals for the
two principal tensor components xyz and yyy. First principles calculation of
the linear and nonlinear optical susceptibilities for Yttrium Aluminum Borate
YAl3(BO3)4 (YAB) crystal have been carried out within a framework of the
full-potential linear augmented plane wave (FP-LAPW) method. Our calculations
show a large anisotropy of the linear and nonlinear optical susceptibilities.
The observed dependences of the second order susceptibilities for the static
frequency limit and for the frequency may be a consequence of different
contribution of electron-phonon interactions. The imaginary parts of the second
order SHG susceptibility chi_{123}^{(2)}(omega), chi_{112}^{(2)}(omega),
chi_{222}^{(2)}(omega), and chi_{213}^{(2)}(omega) are evaluated. We find that
the 2(omega) inter-band and intra-band contributions to the real and imaginary
parts of chi_{ijk}^{(2)}\l(omega) show opposite signs. The calculated second
order susceptibilities are in reasonably good agreement with the experimental
measurements.Comment: 16 pages, 11 figure
Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways
Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To “humanize” this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy. Keywords: alpha-synuclein; iPS cell;
Parkinson’s disease; stem cell; mRNA translation; RNA-binding protein;
LRRK2; VPS35; vesicle trafficking; yeas
The HSP70 Molecular Chaperone Is Not Beneficial in a Mouse Model of α-synucleinopathy
BACKGROUND: Aggregation and misfolded alpha-synuclein is thought to be central in the pathogenesis of Parkinson's disease (PD). Heat-shock proteins (HSPs) that are involved in refolding and degradation processes could lower the aggregate load of alpha-synuclein and thus be beneficial in alpha-synucleinopathies. METHODOLOGY/PRINCIPAL FINDINGS: We co-overexpressed human A53T point-mutated alpha-synuclein and human HSP70 in mice, both under the control of Thy1 regulatory sequences. Behavior read-outs showed no beneficial effect of HSP70 expression in mice. In contrast, motor coordination, grip strength and weight were even worse in the alpha-synucleinopathy model in the presence of HSP70 overexpression. Biochemical analyses revealed no differences in alpha-synuclein oligomers/aggregates, truncations and phosphorylation levels and alpha-synuclein localization was unchanged in immunostainings. CONCLUSION/SIGNIFICANCE: Overexpressing HSP70 in a mouse model of alpha-synucleinopathy did not lower the toxic load of alpha-synuclein species and had no beneficial effect on alpha-synuclein-related motor deficits
Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels
10 pages, 5 figures. 21779322[PubMed] PMCID: PMC3136927BACKGROUND: Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila.
METHODOLOGY/PRINCIPAL FINDINGS: We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant.
CONCLUSION/SIGNIFICANCE: Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels.This work was supported by grants from Fondo Investigaciones Sanitarias (ISCIII06- PI0677) and La Fundació la Marató TV3 (exp 101932) of Spain. JVL is supported by the European Friedreich's Ataxia Consortium for Translational Studies. SS is a recipient of a fellowship from Ministerio de Ciencia e Innovación of Spain.Peer reviewe
Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.
α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the
Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College,
Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals
(CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm
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