4,309 research outputs found
Insights into the In Vivo Regulation of Glutamate Dehydrogenase from the Foot Muscle of an Estivating Land Snail
Land snails, Otala lactea, survive in seasonally hot and dry environments by entering a state of aerobic torpor called estivation. During estivation, snails must prevent excessive dehydration and reorganize metabolic fuel use so as to endure prolonged periods without food. Glutamate dehydrogenase (GDH) was hypothesized to play a key role during estivation as it shuttles amino acid carbon skeletons into the Krebs cycle for energy production and is very important to urea biosynthesis (a key molecule used for water retention). Analysis of purified foot muscle GDH from control and estivating conditions revealed that estivated GDH was approximately 3-fold more active in catalyzing glutamate deamination as compared to control. This kinetic difference appears to be regulated by reversible protein phosphorylation, as indicated by ProQ Diamond phosphoprotein staining and incubations that stimulate endogenous protein kinases and phosphatases. The increased activity of the high-phosphate form of GDH seen in the estivating land snail foot muscle correlates well with the increased use of amino acids for energy and increased synthesis of urea for water retention during prolonged estivation
TSC22 in mammary gland development and breast cancer
Mammary gland involution is characterised by a high degree of apoptosis. By identifying genes that are upregulated at this developmental stage, we aimed to discover key factors that are involved in the induction of mammary epithelial cell death and therefore present potential tumour suppressors for breast cancer. Among 96 genes recently identified as specifically upregulated early during involution were the transforming growth factor beta (TGFβ)-stimulated clone 22 homologue (TSC-22/TGFβ1-induced transcript 4) and TGFβ3 [1]. TGFβ3 has recently been shown to be necessary for induction of apoptosis during mammary gland involution, while TSC-22 overexpression can lead to cell death. We have therefore tested whether TSC-22 mRNA expression can be induced by TGFβ3 and whether it is involved in or necessary for TGFβ-induced apoptosis. We further show that TSC-22 can enhance TGFβ3-induced Smad response and epithelial cell death. In addition, overexpression of TSC-22 alone can induce a Smad response and apoptosis in mammary epithelial cell cultures, which is independent of p53. Further, we have performed tests to study the necessity for Smad proteins during TSC-22-induced apoptosis, and to establish the intracellular localisation of TSC-22. A pilot study on a small cohort of archival breast cancer cases, representing all stages of malignant progression, shows that TSC-22 protein was reduced or undetectable in 60% of breast carcinomas when compared with adjacent normal breast tissue, suggesting that TSC-22 could indeed be a potential novel tumour suppressor gene. We shall present data showing that methylation of the TSC-22 promoter is not involved in the reduction of TSC-22 protein in breast cancer
Purification and properties of white muscle lactate dehydrogenase from the anoxia-tolerant turtle, the red-eared slider, trachemys scripta elegans
Lactate dehydrogenase (LDH; E.C. 1.1.1.27) is a crucial enzyme involved in energy metabolism in muscle, facilitating the production of ATP via glycolysis during oxygen deprivation by recycling NAD+. The present study investigated purified LDH from the muscle of 20 h anoxic and normoxic T. s. elegans, and LDH from anoxic muscle showed a significantly lower (47%) K m for L-lactate and a higher V max value than the normoxic form. Several lines of evidence indicated that LDH was converted to a low phosphate form under anoxia: (a) stimulation of endogenously present protein phosphatases decreased the K m of L-lactate of control LDH to anoxic levels, whereas (b) stimulation of kinases increased the K m of L-lactate of anoxic LDH to normoxic levels, and (c) dot blot analysis shows significantly less serine (78%) and threonine (58%) phosphorylation in anoxic muscle LDH as compared to normoxic LDH. The physiological consequence of anoxia-induced LDH dephosphorylation appears to be an increase in LDH activity to promote the reduction of pyruvate in muscle tissue, converting the glycolytic end product to lactate to maintain a prolonged glycolytic flux under energy-stressed anoxic conditions
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Metatranscriptomic Sequencing of a Cyanobacterial Soil-Surface Consortium with and without a Diverse Underlying Soil Microbiome.
Soil surface consortia are easily observed and sampled, allowing examination of their interactions with soil microbiomes. Here, we present metatranscriptomic sequences from Dark Green 1 (DG1), a cyanobacterium-based soil surface consortium, in the presence and absence of an underlying soil microbiome and/or urea
Emergent Semiclassical Time in Quantum Gravity. I. Mechanical Models
Strategies intended to resolve the problem of time in quantum gravity by
means of emergent or hidden timefunctions are considered in the arena of
relational particle toy models. In situations with `heavy' and `light' degrees
of freedom, two notions of emergent semiclassical WKB time emerge; these are
furthermore equivalent to two notions of emergent classical
`Leibniz--Mach--Barbour' time. I futhermore study the semiclassical approach,
in a geometric phase formalism, extended to include linear constraints, and
with particular care to make explicit those approximations and assumptions
used. I propose a new iterative scheme for this in the cosmologically-motivated
case with one heavy degree of freedom. I find that the usual semiclassical
quantum cosmology emergence of time comes hand in hand with the emergence of
other qualitatively significant terms, including back-reactions on the heavy
subsystem and second time derivatives. I illustrate my analysis by taking it
further for relational particle models with linearly-coupled harmonic
oscillator potentials. As these examples are exactly soluble by means outside
the semiclassical approach, they are additionally useful for testing the
justifiability of some of the approximations and assumptions habitually made in
the semiclassical approach to quantum cosmology. Finally, I contrast the
emergent semiclassical timefunction with its hidden dilational Euler time
counterpart.Comment: References Update
Unbounded violation of tripartite Bell inequalities
We prove that there are tripartite quantum states (constructed from random
unitaries) that can lead to arbitrarily large violations of Bell inequalities
for dichotomic observables. As a consequence these states can withstand an
arbitrary amount of white noise before they admit a description within a local
hidden variable model. This is in sharp contrast with the bipartite case, where
all violations are bounded by Grothendieck's constant. We will discuss the
possibility of determining the Hilbert space dimension from the obtained
violation and comment on implications for communication complexity theory.
Moreover, we show that the violation obtained from generalized GHZ states is
always bounded so that, in contrast to many other contexts, GHZ states do in
this case not lead to extremal quantum correlations. The results are based on
tools from the theories of operator spaces and tensor norms which we exploit to
prove the existence of bounded but not completely bounded trilinear forms from
commutative C*-algebras.Comment: Substantial changes in the presentation to make the paper more
accessible for a non-specialized reade
The cometary composition of a protoplanetary disk as revealed by complex cyanides
Observations of comets and asteroids show that the Solar Nebula that spawned
our planetary system was rich in water and organic molecules. Bombardment
brought these organics to the young Earth's surface, seeding its early
chemistry. Unlike asteroids, comets preserve a nearly pristine record of the
Solar Nebula composition. The presence of cyanides in comets, including 0.01%
of methyl cyanide (CH3CN) with respect to water, is of special interest because
of the importance of C-N bonds for abiotic amino acid synthesis. Comet-like
compositions of simple and complex volatiles are found in protostars, and can
be readily explained by a combination of gas-phase chemistry to form e.g. HCN
and an active ice-phase chemistry on grain surfaces that advances
complexity[3]. Simple volatiles, including water and HCN, have been detected
previously in Solar Nebula analogues - protoplanetary disks around young stars
- indicating that they survive disk formation or are reformed in situ. It has
been hitherto unclear whether the same holds for more complex organic molecules
outside of the Solar Nebula, since recent observations show a dramatic change
in the chemistry at the boundary between nascent envelopes and young disks due
to accretion shocks[8]. Here we report the detection of CH3CN (and HCN and
HC3N) in the protoplanetary disk around the young star MWC 480. We find
abundance ratios of these N-bearing organics in the gas-phase similar to
comets, which suggests an even higher relative abundance of complex cyanides in
the disk ice. This implies that complex organics accompany simpler volatiles in
protoplanetary disks, and that the rich organic chemistry of the Solar Nebula
was not unique.Comment: Definitive version of the manuscript is published in Nature, 520,
7546, 198, 2015. This is the author's versio
E2F1 drives chemotherapeutic drug resistance via ABCG2
Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy
The stellar halo of the Galaxy
Stellar halos may hold some of the best preserved fossils of the formation
history of galaxies. They are a natural product of the merging processes that
probably take place during the assembly of a galaxy, and hence may well be the
most ubiquitous component of galaxies, independently of their Hubble type. This
review focuses on our current understanding of the spatial structure, the
kinematics and chemistry of halo stars in the Milky Way. In recent years, we
have experienced a change in paradigm thanks to the discovery of large amounts
of substructure, especially in the outer halo. I discuss the implications of
the currently available observational constraints and fold them into several
possible formation scenarios. Unraveling the formation of the Galactic halo
will be possible in the near future through a combination of large wide field
photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes.
Full-resolution version available at
http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd
Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC
The uncertainty on the calorimeter energy response to jets of particles is
derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the
calorimeter response to single isolated charged hadrons is measured and
compared to the Monte Carlo simulation using proton-proton collisions at
centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009
and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter
response to specific types of particles (positively and negatively charged
pions, protons, and anti-protons) is measured and compared to the Monte Carlo
predictions. Finally, the jet energy scale uncertainty is determined by
propagating the response uncertainty for single charged and neutral particles
to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3%
for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table,
submitted to European Physical Journal
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