723 research outputs found
Proteomic approaches to study cysteine oxidation: applications in neurodegenerative diseases
Oxidative stress appears to be a key feature of many neurodegenerative diseases either as a cause or consequence of disease. A range of molecules are subject to oxidation, but in particular, proteins are an important target and measure of oxidative stress. Proteins are subject to a range of oxidative modifications at reactive cysteine residues, and depending on the level of oxidative stress, these modifications may be reversible or irreversible. A range of experimental approaches has been developed to characterize cysteine oxidation of proteins. In particular, mass spectrometry-based proteomic methods have emerged as a powerful means to identify and quantify cysteine oxidation sites on a proteome scale; however, their application to study neurodegenerative diseases is limited to date. Here we provide a guide to these approaches and highlight the under-exploited utility of these methods to measure oxidative stress in neurodegenerative diseases for biomarker discovery, target engagement and to understand disease mechanisms
Systematic model behavior of adsorption on flat surfaces
A low density film on a flat surface is described by an expansion involving
the first four virial coefficients. The first coefficient (alone) yields the
Henry's law regime, while the next three correct for the effects of
interactions. The results permit exploration of the idea of universal
adsorption behavior, which is compared with experimental data for a number of
systems
Phenotypic spectrum in osteogenesis imperfecta due to mutations in TMEM38B: unravelling a complex cellular defect.
Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy. Bone biopsy samples (n=3) were analysed using histomorphometry, quantitative backscattered electron microscopy and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Results: The clinical phenotype of type XIV OI ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband L1-L4 bone density Z-score was reduced (median -3.3 [range -4.77 to +0.1; n=7]), and increased by +1.7 (1.17 to 3.0; n=3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased late and mineralization-related markers. Predominance of TRIC-B over TRIC-A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. Conclusions: OI type XIV has a bone histology, matrix mineralization and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities
Developmental changes in word recognition threshold from two to five years of age in children with different middle ear status
The aims were to: (1) provide word recognition thresholds (WRTs) at 31, 43, and 61 months of age; (2) investigate developmental changes over time; (3) investigate the relationship between OME and WRT, and (4) investigate the relationship between WRT and hearing thresholds. Around 1000 children were tested longitudinally as part of the ALSPAC study, using an adaptive measure of word recognition in quiet. Mean WRTs were 28, 23, and 23 dB (A) at 31, 43, and 61 months, respectively. Normal auditory development is associated with a mean improvement in WRT of 5 dB between age 31 and 61 months. There was a mean increase in WRT of 5 dB and 15 dB when OME was present in one and two ears, respectively. Thus, both unilateral and bilateral OME results in a detrimental effect on hearing ability for speech. Additionally, early and ‘persistent’ OME is associated with greater disability. However by 61 months, previous OME status was not significant. To our knowledge, this is the largest longitudinal study reporting WRT in preschool children with different middle ear status
A determination of the pairing interaction in the high Tc cuprate superconductor Tl2Ba2CaCu2O8 (Tl2212)
We have measured the near-normal reflectance of Tl2Ba2CaCu2O8 (Tl2212) for
energies from 0.1 to 4.0 eV at room temperature and used a Kramers-Kronig
analysis to find the complex, frequency dependent dielectric function, from
which the optical conductivity was determined. Using
Thermal-Difference-Reflectance (TDR) Spectroscopy the reflectance of the sample
in the normal state just above the superconducting transition, and in the
superconducting state were then obtained. From these data we determined the
ratio of the superconducting- to normal-state optical conductivities. Mattis
and Bardeen had calculated this function within the BCS theory, where the gap
is a fixed energy-independent quantity. Taking into account the retarded nature
of the electron-phonon coupling results in a complex, energy dependent gap
causing deviations from the Mattis-Bardeen plot at energies where the phonon
coupling function is large. We find a typical deviation near the phonon
energies in Tl2212, and in addition, at 1.2 and 1.7eV. The phonon, and these
electronic terms can each be described by a coupling constant. None of which by
itself gives rise to a high transition temperature, but the combination does.
Using Resonant Inelastic X-Ray Scattering (RIXS) we find that the d-to-d
excitations of the cuprate ion in Tl2212 fall at the same energies as the dips
in the Mattis-Bardeen plot. We conclude that the high superconducting
transition temperature of the cuprates is due to the sum of the phonon
interaction, and interactions with the Cu-ion d-shell.Comment: Preprint submitted to Physica C. Paper presented at M2S-HTSC-VIII,
Dresden, Germany, July 9-14,200
Heavy Quarks and Heavy Quarkonia as Tests of Thermalization
We present here a brief summary of new results on heavy quarks and heavy
quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma
Thermalization" Workshop in Vienna, Austria in August 2005, directly following
the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop
(Vienna August 2005) Proceeding
Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV
The invariant differential cross section for inclusive electron production in
p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment
at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4
<= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the
inclusive electron spectrum from semileptonic decays of hadrons carrying heavy
flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via
three independent methods. The resulting electron spectrum from heavy flavor
decays is compared to recent leading and next-to-leading order perturbative QCD
calculations. The total cross section of charm quark-antiquark pair production
is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV
The PHENIX experiment has measured mid-rapidity transverse momentum spectra
(0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au
collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and
from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were
removed. The resulting non-photonic electron spectra are primarily due to the
semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification
factors were determined by comparison to non-photonic electrons in p+p
collisions. A significant suppression of electrons at high p_T is observed in
central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Measurement of Transverse Single-Spin Asymmetries for Mid-rapidity Production of Neutral Pions and Charged Hadrons in Polarized p+p Collisions at sqrt(s) = 200 GeV
The transverse single-spin asymmetries of neutral pions and non-identified
charged hadrons have been measured at mid-rapidity in polarized proton-proton
collisions at sqrt(s) = 200 GeV. The data cover a transverse momentum (p_T)
range 0.5-5.0 GeV/c for charged hadrons and 1.0-5.0 GeV/c for neutral pions, at
a Feynman-x (x_F) value of approximately zero. The asymmetries seen in this
previously unexplored kinematic region are consistent with zero within
statistical errors of a few percent. In addition, the inclusive charged hadron
cross section at mid-rapidity from 0.5 < p_T < 7.0 GeV/c is presented and
compared to NLO pQCD calculations. Successful description of the unpolarized
cross section above ~2 GeV/c using NLO pQCD suggests that pQCD is applicable in
the interpretation of the asymmetry results in the relevant kinematic range.Comment: 331 authors, 6 pages text, 2 figures, 3 tables. Submitted to Phys.
Rev. Lett. Plain text data tables for the points plotted in figures for this
and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration
Extensive experimental data from high-energy nucleus-nucleus collisions were
recorded using the PHENIX detector at the Relativistic Heavy Ion Collider
(RHIC). The comprehensive set of measurements from the first three years of
RHIC operation includes charged particle multiplicities, transverse energy,
yield ratios and spectra of identified hadrons in a wide range of transverse
momenta (p_T), elliptic flow, two-particle correlations, non-statistical
fluctuations, and suppression of particle production at high p_T. The results
are examined with an emphasis on implications for the formation of a new state
of dense matter. We find that the state of matter created at RHIC cannot be
described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted
to Nuclear Physics A as a regular article; v3 has minor changes in response
to referee comments. Plain text data tables for the points plotted in figures
for this and previous PHENIX publications are (or will be) publicly available
at http://www.phenix.bnl.gov/papers.htm
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