202 research outputs found
Misfolding and aggregation of nascent proteins: a novel mode of toxic cadmium action in vivo.
Cadmium is a highly poisonous metal and a human carcinogen, but the molecular mechanisms underlying its cellular toxicity are not fully understood. Recent findings in yeast cells indicate that cadmium exerts its deleterious effects by inducing widespread misfolding and aggregation of nascent proteins. Here, we discuss this novel mode of toxic heavy metal action and propose a mechanism by which molecular chaperones may reduce the damaging effects of heavy metal ions on protein structures
Planck Observations of M33
We have performed a comprehensive investigation of the global integrated flux
density of M33 from radio to ultraviolet wavelengths, finding that the data
between 100 GHz and 3 THz are accurately described by a single modified
blackbody curve with a dust temperature of = 21.670.30 K
and an effective dust emissivity index of = 1.350.10,
with no indication of an excess of emission at millimeter/sub-millimeter
wavelengths. However, sub-dividing M33 into three radial annuli, we found that
the global emission curve is highly degenerate with the constituent curves
representing the sub-regions of M33. We also found gradients in
and across the disk of M33, with both
quantities decreasing with increasing radius. Comparing the M33 dust emissivity
with that of other Local Group members, we find that M33 resembles the
Magellanic Clouds rather than the larger galaxies, i.e., the Milky Way and M31.
In the Local Group sample, we find a clear correlation between global dust
emissivity and metallicity, with dust emissivity increasing with metallicity. A
major aspect of this analysis is the investigation into the impact of
fluctuations in the Cosmic Microwave Background (CMB) on the integrated flux
density spectrum of M33. We found that failing to account for these CMB
fluctuations would result in a significant over-estimate of
by 5 K and an under-estimate of by 0.4.Comment: Accepted for publication in MNRA
Bacterial Hsp90 Facilitates the Degradation of Aggregation-Prone Hsp70-Hsp40 Substrates.
In eukaryotes, the 90-kDa heat shock proteins (Hsp90s) are profusely studied chaperones that, together with 70-kDa heat shock proteins (Hsp70s), control protein homeostasis. In bacteria, however, the function of Hsp90 (HtpG) and its collaboration with Hsp70 (DnaK) remains poorly characterized. To uncover physiological processes that depend on HtpG and DnaK, we performed comparative quantitative proteomic analyses of insoluble and total protein fractions from unstressed wild-type (WT) Escherichia coli and from knockout mutants ÎdnaKdnaJ (ÎKJ), ÎhtpG (ÎG), and ÎdnaKdnaJÎhtpG (ÎKJG). Whereas the ÎG mutant showed no detectable proteomic differences with wild-type, ÎKJ expressed more chaperones, proteases and ribosomes and expressed dramatically less metabolic and respiratory enzymes. Unexpectedly, we found that the triple mutant ÎKJG showed higher levels of metabolic and respiratory enzymes than ÎKJ, suggesting that bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70-Hsp40 substrates. Further in vivo experiments suggest that such Hsp90-mediated degradation possibly occurs through the HslUV protease
In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells
α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinsonâs disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution
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Impact of particles on the Planck HFI detectors: Ground-based measurements and physical interpretation
The Planck High Frequency Instrument (HFI) surveyed the sky continuously from
August 2009 to January 2012. Its noise and sensitivity performance were
excellent, but the rate of cosmic ray impacts on the HFI detectors was
unexpectedly high. Furthermore, collisions of cosmic rays with the focal plane
produced transient signals in the data (glitches) with a wide range of
characteristics. A study of cosmic ray impacts on the HFI detector modules has
been undertaken to categorize and characterize the glitches, to correct the HFI
time-ordered data, and understand the residual effects on Planck maps and data
products. This paper presents an evaluation of the physical origins of glitches
observed by the HFI detectors. In order to better understand the glitches
observed by HFI in flight, several ground-based experiments were conducted with
flight-spare HFI bolometer modules. The experiments were conducted between 2010
and 2013 with HFI test bolometers in different configurations using varying
particles and impact energies. The bolometer modules were exposed to 23 MeV
protons from the Orsay IPN TANDEM accelerator, and to Am and Cm
-particle and Fe radioactive X-ray sources. The calibration data
from the HFI ground-based preflight tests were used to further characterize the
glitches and compare glitch rates with statistical expectations under
laboratory conditions. Test results provide strong evidence that the dominant
family of glitches observed in flight are due to cosmic ray absorption by the
silicon die substrate on which the HFI detectors reside. Glitch energy is
propagated to the thermistor by ballistic phonons, while there is also a
thermal diffusion contribution. The implications of these results for future
satellite missions, especially those in the far-infrared to sub-millimetre and
millimetre regions of the electromagnetic spectrum, are discussed.Comment: 11 pages, 13 figure
The pre-launch Planck Sky Model: a model of sky emission at submillimetre to centimetre wavelengths
We present the Planck Sky Model (PSM), a parametric model for the generation
of all-sky, few arcminute resolution maps of sky emission at submillimetre to
centimetre wavelengths, in both intensity and polarisation. Several options are
implemented to model the cosmic microwave background, Galactic diffuse emission
(synchrotron, free-free, thermal and spinning dust, CO lines), Galactic H-II
regions, extragalactic radio sources, dusty galaxies, and thermal and kinetic
Sunyaev-Zeldovich signals from clusters of galaxies. Each component is
simulated by means of educated interpolations/extrapolations of data sets
available at the time of the launch of the Planck mission, complemented by
state-of-the-art models of the emission. Distinctive features of the
simulations are: spatially varying spectral properties of synchrotron and dust;
different spectral parameters for each point source; modeling of the clustering
properties of extragalactic sources and of the power spectrum of fluctuations
in the cosmic infrared background. The PSM enables the production of random
realizations of the sky emission, constrained to match observational data
within their uncertainties, and is implemented in a software package that is
regularly updated with incoming information from observations. The model is
expected to serve as a useful tool for optimizing planned microwave and
sub-millimetre surveys and to test data processing and analysis pipelines. It
is, in particular, used for the development and validation of data analysis
pipelines within the planck collaboration. A version of the software that can
be used for simulating the observations for a variety of experiments is made
available on a dedicated website.Comment: 35 pages, 31 figure
Magnetic Fields in the Milky Way
This chapter presents a review of observational studies to determine the
magnetic field in the Milky Way, both in the disk and in the halo, focused on
recent developments and on magnetic fields in the diffuse interstellar medium.
I discuss some terminology which is confusingly or inconsistently used and try
to summarize current status of our knowledge on magnetic field configurations
and strengths in the Milky Way. Although many open questions still exist, more
and more conclusions can be drawn on the large-scale and small-scale components
of the Galactic magnetic field. The chapter is concluded with a brief outlook
to observational projects in the near future.Comment: 22 pages, 5 figures, to appear in "Magnetic Fields in Diffuse Media",
eds. E.M. de Gouveia Dal Pino and A. Lazaria
Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins.
During and after protein translation, molecular chaperones require ATP hydrolysis to favor the native folding of their substrates and, under stress, to avoid aggregation and revert misfolding. Why do some chaperones need ATP, and what are the consequences of the energy contributed by the ATPase cycle? Here, we used biochemical assays and physical modeling to show that the bacterial chaperones GroEL (Hsp60) and DnaK (Hsp70) both use part of the energy from ATP hydrolysis to restore the native state of their substrates, even under denaturing conditions in which the native state is thermodynamically unstable. Consistently with thermodynamics, upon exhaustion of ATP, the metastable native chaperone products spontaneously revert to their equilibrium non-native states. In the presence of ATPase chaperones, some proteins may thus behave as open ATP-driven, nonequilibrium systems whose fate is only partially determined by equilibrium thermodynamics
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