355 research outputs found
The use of urinary proteomics in the assessment of suitability of mouse models for ageing
Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8–96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing
A Distance-Limited Imaging Survey of Sub-Stellar Companions to Solar Neighborhood Stars
We report techniques and results of a Palomar 200-inch (5 m) adaptive optics
imaging survey of sub-stellar companions to solar-type stars. The survey
consists of Ks coronagraphic observations of 21 FGK dwarfs out to 20 pc (median
distance about 17 pc). At 1-arcsec separation (17 projected AU) from a typical
target system, the survey achieves median sensitivities 7 mag fainter than the
parent star. In terms of companion mass, that corresponds to sensitivities of
50MJ (1 Gyr), 70MJ (solar age), and 75MJ (10 Gyr), using the evolutionary
models of Baraffe and colleagues. Using common proper motion to distinguish
companions from field stars, we find that no system shows positive evidence of
a previously unknown substellar companion (searchable separation about 20-250
projected AU at the median target distance).Comment: 29 pages, 5 figures. Carson et al. 2008, AJ, in pres
Protein Kinase D2 Is an Essential Regulator of Murine Myoblast Differentiation
Muscle differentiation is a highly conserved process that occurs through the activation of quiescent satellite cells whose progeny proliferate, differentiate, and fuse to generate new myofibers. A defined pattern of myogenic transcription factors is orchestrated during this process and is regulated via distinct signaling cascades involving various intracellular signaling pathways, including members of the protein kinase C (PKC) family. The protein kinase D (PKD) isoenzymes PKD1, -2, and -3, are prominent downstream targets of PKCs and phospholipase D in various biological systems including mouse and could hence play a role in muscle differentiation. In the present study, we used a mouse myoblast cell line (C2C12) as an in vitro model to investigate the role of PKDs, in particular PKD2, in muscle stem cell differentiation. We show that C2C12 cells express all PKD isoforms with PKD2 being highly expressed. Furthermore, we demonstrate that PKD2 is specifically phosphorylated/activated during the initiation of mouse myoblast differentiation. Selective inhibition of PKCs or PKDs by pharmacological inhibitors blocked myotube formation. Depletion of PKD2 by shRNAs resulted in a marked inhibition of myoblast cell fusion. PKD2-depleted cells exhibit impaired regulation of muscle development-associated genes while the proliferative capacity remains unaltered. Vice versa forced expression of PKD2 increases myoblast differentiation. These findings were confirmed in primary mouse satellite cells where myotube fusion was also decreased upon inhibition of PKDs. Active PKD2 induced transcriptional activation of myocyte enhancer factor 2D and repression of Pax3 transcriptional activity. In conclusion, we identify PKDs, in particular PKD2, as a major mediator of muscle cell differentiation in vitro and thereby as a potential novel target for the modulation of muscle regeneration
Feedback between p21 and reactive oxygen production is necessary for cell senescence
The sustained activation of CDKN1A (p21/Waf1/Cip1) by a DNA damage response induces mitochondrial dysfunction and reactive oxygen species (ROS) production via signalling through CDKN1A-GADD45A-MAPK14- GRB2-TGFBR2-TGFbeta in senescing primary human and mouse cells in vitro and in vivo.Enhanced ROS production in senescing cells generates additional DNA damage. Although this damage is repairable and transient, it elevates the average levels of DNA damage response permanently, thus forming a positive feedback loop.This loop is necessary and sufficient to maintain the stability of growth arrest until a ‘point of no return' is reached during establishment of senescence
Intrinsic gain modulation and adaptive neural coding
In many cases, the computation of a neural system can be reduced to a
receptive field, or a set of linear filters, and a thresholding function, or
gain curve, which determines the firing probability; this is known as a
linear/nonlinear model. In some forms of sensory adaptation, these linear
filters and gain curve adjust very rapidly to changes in the variance of a
randomly varying driving input. An apparently similar but previously unrelated
issue is the observation of gain control by background noise in cortical
neurons: the slope of the firing rate vs current (f-I) curve changes with the
variance of background random input. Here, we show a direct correspondence
between these two observations by relating variance-dependent changes in the
gain of f-I curves to characteristics of the changing empirical
linear/nonlinear model obtained by sampling. In the case that the underlying
system is fixed, we derive relationships relating the change of the gain with
respect to both mean and variance with the receptive fields derived from
reverse correlation on a white noise stimulus. Using two conductance-based
model neurons that display distinct gain modulation properties through a simple
change in parameters, we show that coding properties of both these models
quantitatively satisfy the predicted relationships. Our results describe how
both variance-dependent gain modulation and adaptive neural computation result
from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio
A Spitzer Space Telescope far-infrared spectral atlas of compact sources in the Magellanic Clouds. I. The Large Magellanic Cloud
[abridged] We present 52-93 micron spectra obtained with Spitzer in the
MIPS-SED mode, of a representative sample of luminous compact far-IR sources in
the LMC. These include carbon stars, OH/IR AGB stars, post-AGB objects and PNe,
RCrB-type star HV2671, OH/IR red supergiants WOHG064 and IRAS05280-6910, B[e]
stars IRAS04530-6916, R66 and R126, Wolf-Rayet star Brey3a, Luminous Blue
Variable R71, supernova remnant N49, a large number of young stellar objects,
compact HII regions and molecular cores, and a background galaxy (z~0.175). We
use the spectra to constrain the presence and temperature of cold dust and the
excitation conditions and shocks within the neutral and ionized gas, in the
circumstellar environments and interfaces with the surrounding ISM. Evolved
stars, including LBV R71, lack cold dust except in some cases where we argue
that this is swept-up ISM. This leads to an estimate of the duration of the
prolific dust-producing phase ("superwind") of several thousand years for both
RSGs and massive AGB stars, with a similar fractional mass loss experienced
despite the different masses. We tentatively detect line emission from neutral
oxygen in the extreme RSG WOHG064, with implications for the wind driving. In
N49, the shock between the supernova ejecta and ISM is revealed by its strong
[OI] 63-micron emission and possibly water vapour; we estimate that 0.2 Msun of
ISM dust was swept up. Some of the compact HII regions display pronounced
[OIII] 88-micron emission. The efficiency of photo-electric heating in the
interfaces of ionized gas and molecular clouds is estimated at 0.1-0.3%. We
confirm earlier indications of a low nitrogen content in the LMC. Evidence for
solid state emission features is found in both young and evolved object; some
of the YSOs are found to contain crystalline water ice.Comment: Accepted for publication in The Astronomical Journal. This paper
accompanies the Summer 2009 SAGE-Spec release of 48 MIPS-SED spectra, but
uses improved spectrum extraction. (Fig. 2 reduced resolution because of
arXiv limit.
UBVRI Light Curves of 44 Type Ia Supernovae
We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from
1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence
Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The
data set comprises 2190 observations and is the largest homogeneously observed
and reduced sample of SN Ia to date, nearly doubling the number of
well-observed, nearby SN Ia with published multicolor CCD light curves. The
large sample of U-band photometry is a unique addition, with important
connections to SN Ia observed at high redshift. The decline rate of SN Ia
U-band light curves correlates well with the decline rate in other bands, as
does the U-B color at maximum light. However, the U-band peak magnitudes show
an increased dispersion relative to other bands even after accounting for
extinction and decline rate, amounting to an additional ~40% intrinsic scatter
compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication
in the Astronomical Journal. Version with high-res figures and electronic
data at http://astron.berkeley.edu/~saurabh/cfa2snIa
International Circumpolar Surveillance System for Invasive Pneumococcal Disease, 1999–2005
Disease rates are high among indigenous persons in Arctic countries, and PCV7 has resulted in decreased rates in North American children
Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV
Results are presented from a search for physics beyond the standard model
based on events with large missing transverse energy, at least three jets, and
at least one, two, or three b-quark jets. The study is performed using a sample
of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS
detector at the LHC in 2011. The integrated luminosity of the sample is 4.98
inverse femtobarns. The observed number of events is found to be consistent
with the standard model expectation, which is evaluated using control samples
in the data. The results are used to constrain cross sections for the
production of supersymmetric particles decaying to b-quark-enriched final
states in the context of simplified model spectra.Comment: Submitted to Physical Review
How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property
The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe
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