514 research outputs found
Role of spinon and spinon singlet pair excitations on phase transitions in superconductors
We examine the roles of massless Dirac spinon and spin singlet pair
excitations on the phase transition in superconductors. Although the
massless spinon excitations in the presence of the spin singlet pair
excitations do not alter the nature of the phase transition at , that
is, the XY universality class, they are seen to induce an additional attractive
interaction potential between vortices, further stabilizing vortex-antivortex
pairs at low temperature for lightly doped high samples.Comment: 5 pages, 1 figur
Conformational heterogeneity of the Roc domains in C. tepidum Roc-COR and implications for human LRRK2 Parkinson mutations
Ras of complex proteins (Roc) is a Ras-like GTP binding domain that always occurs in tandem with the C-terminal of Roc (COR) domain, and is found in bacteria, plants and animals. Recently, it has been shown that Roco proteins belong to the family of G-proteins activated by nucleotide-dependent dimerization (GADs). We investigated the RocCOR tandem from the bacteria Chlorobium tepidum with site-directed spin labeling and pulse EPR distance measurements to follow conformational changes during the Roco G-protein cycle. Our results confirm that the COR domains are a stable dimerization device serving as a scaffold for the Roc domains, that in contrast are structurally heterogeneous and dynamic entities. Contrary to other GAD proteins, we observed only minor structural alterations upon binding and hydrolysis of GTP, indicating significant mechanistic variations within this protein class. Mutations in the most prominent member of the Roco family of proteins, leucine-rich repeat kinase 2 (LRRK2), are the most frequent cause of late-onset Parkinson's disease (PD). Using a stable recombinant LRRK2 Roc-COR-Kinase fragment we obtained detailed kinetic data for the G-protein cycle. Our data confirmed that dimerization is essential for efficient GTP hydrolysis, and PD mutations in the Roc domain result in decreased GTPase activity. Previous data have shown that these LRRK2 PD-mutations are located in the interface between Roc and COR. Importantly, analogous mutations in the conserved C. tepidum RocCOR interface significantly influence the structure and nucleotide-induced conformational changes of the Roc domains
Particle-hole symmetry and transport properties of the flux state in underdoped cuprates
Transport properties are studied for the flux state with the gauge flux
per plaquett, which may model the underdoped cuprates, with the emphasis
on the particle-hole and parity/chiral symmetries.This model is reduced to the
Dirac fermions in (2+1)D with a mass gap introduced by the antiferromagnetic
(AF) long range order and/or the stripe formation. Without the mass gap, the
Hall constant and the thermopower obey two-parameter scaling laws,
and show the strong temperature dependence due to the recovery of the
particle-hole symmetry at high temperature. The -dependences of and (independent of ) are in a sharp
contradiction with the experiments. (Here is the hole concentration.)
Therefore there is no signature of the particle-hole symmetry or the massless
Dirac fermions in the underdoped cuprates even above the Neel temperature
. With the mass gap introduced by the AF order, there occurs the parity
anomaly for each of the Dirac fermions. However the contributions from
different valleys and spins cancel with each other to result in no spontaneous
Hall effect even if the time-reversal symmetry is broken with .
The effects of the stripes are also studied. The diagonal and vertical
(horizontal) stripes have quite different influence on the transport
properties. The suppression of occurs at low temperature only when (i)
both the AF order and the vertical (horizontal) stripe coexist, and (ii) the
average over the in-plane direction is taken. Discussions on the recent
experiments are given from the viewpoint of these theoretical results.Comment: RevTeX, 14 pages, 11 figure
Doubly Constrained C-terminal of Roc (COR) Domain-Derived Peptides Inhibit Leucine-Rich Repeat Kinase 2 (LRRK2) Dimerization
Missense mutations along the leucine-rich repeat kinase 2 (LRRK2) protein are a major contributor to Parkinson's Disease (PD), the second most commonly occurring neurodegenerative disorder worldwide. We recently reported the development of allosteric constrained peptide inhibitors that target and downregulate LRRK2 activity through disruption of LRRK2 dimerization. In this study, we designed doubly constrained peptides with the objective of inhibiting C-terminal of Roc (COR)-COR mediated dimerization at the LRRK2 dimer interface. We show that the doubly constrained peptides are cell-permeant, bind wild-type and pathogenic LRRK2, inhibit LRRK2 dimerization and kinase activity, and inhibit LRRK2-mediated neuronal apoptosis, and in contrast to ATP-competitive LRRK2 kinase inhibitors, they do not induce the mislocalization of LRRK2 to skein-like structures in cells. This work highlights the significance of COR-mediated dimerization in LRRK2 activity while also highlighting the use of doubly constrained peptides to stabilize discrete secondary structural folds within a peptide sequence.</p
The Roc domain of LRRK2 as a hub for protein-protein interactions:a focus on PAK6 and its impact on RAB phosphorylation
Leucine-rich repeat kinase 2 (LRRK2) has taken center stage in Parkinson's disease (PD) research as mutations cause familial PD and more common variants increase lifetime risk for disease. One unique feature in LRRK2 is the coexistence of GTPase/Roc (Ras of complex) and kinase catalytic functions, bridged by a COR (C-terminal Of Roc) platform for dimerization. Multiple PD mutations are located within the Roc/GTPase domain and concomitantly lead to defective GTPase activity and augmented kinase activity in cells, supporting a crosstalk between GTPase and kinase domains. In addition, biochemical and structural data highlight the importance of Roc as a molecular switch modulating LRRK2 monomer-to-dimer equilibrium and building the interface for interaction with binding partners. Here we review the effects of PD Roc mutations on LRRK2 function and discuss the importance of Roc as a hub for multiple molecular interactions relevant for the regulation of cytoskeletal dynamics and intracellular trafficking pathways. Among the well-characterized Roc interactors, we focused on the cytoskeletal-related kinase p21-activated kinase 6 (PAK6). We report the affinity between LRRK2-Roc and PAK6 measured by microscale thermophoresis (MST). We further show that PAK6 can modulate LRRK2-mediated phosphorylation of RAB substrates in the presence of LRRK2 wild-type (WT) or the PD G2019S kinase mutant but not when the PD Roc mutation R1441G is expressed. These findings support a mechanism whereby mutations in Roc might affect LRRK2 activity through impaired protein-protein interaction in the cell
Allosteric Inhibition of Parkinson's-Linked LRRK2 by Constrained Peptides
Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multidomain protein with dual kinase and GTPase function that is commonly mutated in both familial and idiopathic Parkinson's Disease (PD). While dimerization of LRRK2 is commonly detected in PD models, it remains unclear whether inhibition of dimerization can regulate catalytic activity and pathogenesis. Here, we show constrained peptides that are cell-penetrant, bind LRRK2, and inhibit LRRK2 activation by downregulating dimerization. We further show that inhibited dimerization decreases kinase activity and inhibits ROS production and PD-linked apoptosis in primary cortical neurons. While many ATP-competitive LRRK2 inhibitors induce toxicity and mislocalization of the protein in cells, these constrained peptides were found to not affect LRRK2 localization. The ability of these peptides to inhibit pathogenic LRRK2 kinase activity suggests that disruption of dimerization may serve as a new allosteric strategy to downregulate PD-related signaling pathways.</p
Flow Measurements via Two-particle Azimuthal Correlations in Au + Au Collisions at sqrt(s_NN) = 130 GeV
Two particle azimuthal correlation functions are presented for charged
hadrons produced in Au + Au collisions at RHIC sqrt(s_NN) = 130 GeV. The
measurements permit determination of elliptic flow without event-by-event
estimation of the reaction plane. The extracted elliptic flow values v_2 show
significant sensitivity to both the collision centrality and the transverse
momenta of emitted hadrons, suggesting rapid thermalization and relatively
strong velocity fields. When scaled by the eccentricity of the collision zone,
epsilon, the scaled elliptic flow shows little or no dependence on centrality
for charged hadrons with relatively low p_T. A breakdown of this epsilon
scaling is observed for charged hadrons with p_T > 1.0 GeV/c for the most
central collisions.Comment: 6 pages, RevTeX 3, 4 figures, 307 authors, submitted to Phys. Rev.
Lett. on 11 April 2002. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (will be made) publicly
available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV
Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the
PHENIX detector at RHIC, are used to investigate local net charge fluctuations
among particles produced near mid-rapidity. According to recent suggestions,
such fluctuations may carry information from the Quark Gluon Plasma. This
analysis shows that the fluctuations are dominated by a stochastic distribution
of particles, but are also sensitive to other effects, like global charge
conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev.
Lett. on 21 March, 2002. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (will be made) publicly
available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Event-by-event fluctuations in Mean and Mean in sqrt(s_NN) = 130 GeV Au+Au Collisions
Distributions of event-by-event fluctuations of the mean transverse momentum
and mean transverse energy near mid-rapidity have been measured in Au+Au
collisions at sqrt(s_NN) = 130 GeV at RHIC. By comparing the distributions to
what is expected for statistically independent particle emission, the magnitude
of non-statistical fluctuations in mean transverse momentum is determined to be
consistent with zero. Also, no significant non-random fluctuations in mean
transverse energy are observed. By constructing a fluctuation model with two
event classes that preserve the mean and variance of the semi-inclusive p_T or
e_T spectra, we exclude a region of fluctuations in sqrt(s_NN) = 130 GeV Au+Au
collisions.Comment: 10 pages, RevTeX 3, 7 figures, 4 tables, 307 authors, submitted to
Phys. Rev. C on 22 March 2002. Plain text data tables for the points plotted
in figures for this and previous PHENIX publications are (will be made)
publicly available at
http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Measurement of the mid-rapidity transverse energy distribution from GeV Au+Au collisions at RHIC
The first measurement of energy produced transverse to the beam direction at
RHIC is presented. The mid-rapidity transverse energy density per participating
nucleon rises steadily with the number of participants, closely paralleling the
rise in charged-particle density, such that E_T / N_ch remains relatively
constant as a function of centrality. The energy density calculated via
Bjorken's prescription for the 2% most central Au+Au collisions at
sqrt(s_NN)=130 GeV is at least epsilon_Bj = 4.6 GeV/fm^3 which is a factor of
1.6 larger than found at sqrt(s_NN)=17.2 GeV (Pb+Pb at CERN).Comment: 307 authors, 6 pages, 4 figures, 1 table, submitted to PRL 4/18/2001;
revised version submitted to PRL 5/24/200
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