1,035 research outputs found
A Crh-specific function in carbon catabolite repression in Bacillus subtilis
Carbon catabolite repression in Bacillus subtilis is mediated by phosphorylation of the phosphoenolpyruvate: carbohydrate phosphotransferase system intermediate HPr at a serine residue catalyzed by HPr kinase. The orthologous protein Crh functions in a similar way, but, unlike HPr, it is not functional in carbohydrate uptake. A specific function for Crh is not known. The role of HPr and Crh in repressing the citM gene encoding the Mg2+-citrate transporter was investigated during growth of B. subtilis on different carbon sources. In glucose minimal medium, full repression was supported by both HPr and Crh. Strains deficient in Crh or the regulatory function of HPr revealed the same repression as the wild-type strain. In contrast, in a medium containing succinate and glutamate, repression was specifically mediated via Crh. Repression was relieved in the Crh-deficient strain, but still present in the HPr mutant strain. The data are the first demonstration of a Crh-specific function in B. subtilis and suggest a role for Crh in regulation of expression during growth on substrates other than carbohydrates. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies
Supersymmetric Charged Clouds in AdS_5
We consider supersymmetric holographic flows that involve background gauge
fields dual to chemical potentials in the boundary field theory. We use a
consistent truncation of gauged N=8 supergravity in five dimensions and we give
a complete analysis of the supersymmetry conditions for a large family of
flows. We examine how the well-known supersymmetric flow between two fixed
points is modified by the presence of the chemical potentials and this yields a
new, completely smooth, solution that interpolates between two global AdS
spaces of different radii and with different values of the chemical potential.
We also examine some black-hole-like singular flows and a new
non-supersymmetric black hole solution. We comment on the interpretation of our
new solutions in terms of giant gravitons and discuss the implications of our
work for finding black-hole solutions in AdS geometries.Comment: 31 pages, 6 figures; minor corrections, updated reference
Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington’s disease
Huntington’s disease (HD) is a late onset, inherited neurodegenerative disorder for which early pathogenic events remain poorly understood. Here we show that mutant exon 1 HTT proteins are recruited to a subset of cytoplasmic aggregates in the cell bodies of neurons in brain sections from presymptomatic HD, but not wild-type, mice. This occurred in a disease stage and polyglutamine-length dependent manner. We successfully adapted a high-resolution correlative light and electron microscopy methodology, originally developed for mammalian and yeast cells, to allow us to correlate light microscopy and electron microscopy images on the same brain section within an accuracy of 100 nm. Using this approach, we identified these recruitment sites as single membrane bound, vesicle-rich endolysosomal organelles, specifically as (1) multivesicular bodies (MVBs), or amphisomes and (2) autolysosomes or residual bodies. The organelles were often found in close-proximity to phagophore-like structures. Immunogold labeling localized mutant HTT to non-fibrillar, electron lucent structures within the lumen of these organelles. In presymptomatic HD, the recruitment organelles were predominantly MVBs/amphisomes, whereas in late-stage HD, there were more autolysosomes or residual bodies. Electron tomograms indicated the fusion of small vesicles with the vacuole within the lumen, suggesting that MVBs develop into residual bodies. We found that markers of MVB-related exocytosis were depleted in presymptomatic mice and throughout the disease course. This suggests that endolysosomal homeostasis has moved away from exocytosis toward lysosome fusion and degradation, in response to the need to clear the chronically aggregating mutant HTT protein, and that this occurs at an early stage in HD pathogenesis
Estimating Dynamic Gait Stability Using Data from Non-aligned Inertial Sensors
Recently, two methods for quantifying the stability of a dynamical system have been applied to human locomotion: local stability (quantified by finite time maximum Lyapunov exponents, λs and λL) and orbital stability (quantified by maximum Floquet multipliers, MaxFm). In most studies published to date, data from optoelectronic measurement systems were used to calculate these measures. However, using wireless inertial sensors may be more practical as they are easier to use, also in ambulatory applications. While inertial sensors have been employed in some studies, it is unknown whether they lead to similar stability estimates as obtained with optoelectronic measurement systems. In the present study, we compared stability measures of human walking estimated from an optoelectronic measurement system with those calculated from an inertial sensor measurement system. Subjects walked on a treadmill at three different speeds while kinematics were recorded using both measurement systems. From the angular velocities and linear accelerations, λs, λL, and MaxFm were calculated. Both measurement systems showed the same effects of walking speed for all variables. Estimates from both measurement systems correlated high for λs and λL, (R > 0.85) but less strongly for MaxFm (R = 0.66). These results indicate that inertial sensors constitute a valid alternative for an optoelectronic measurement system when assessing dynamic stability in human locomotion, and may thus be used instead, which paves the way to studying gait stability during natural, everyday walking
Monitoring Cognitive and Emotional Processes Through Pupil and Cardiac Response During Dynamic Versus Logical Task
The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error
Supergravity Solutions from Floating Branes
We solve the equations of motion of five-dimensional ungauged supergravity
coupled to three U(1) gauge fields using a floating-brane Ansatz in which the
electric potentials are directly related to the gravitational warp factors. We
find a new class of non-BPS solutions, that can be obtained linearly starting
from an Euclidean four-dimensional Einstein-Maxwell base. This class - the
largest known so far - reduces to the BPS and almost-BPS solutions in certain
limits. We solve the equations explicitly when the base space is given by the
Israel-Wilson metric, and obtain solutions describing non-BPS D6 and anti-D6
branes kept in equilibrium by flux. We also examine the action of spectral flow
on solutions with an Israel-Wilson base and show that it relates these
solutions to almost-BPS solutions with a Gibbons-Hawking base.Comment: 24 pages, 1 figur
An Infinite-Dimensional Family of Black-Hole Microstate Geometries
We construct the first explicit, smooth, horizonless black-hole microstate
geometry whose moduli space is described by an arbitrary function of one
variable and is thus infinite-dimensional. This is achieved by constructing the
scalar Green function on a simple D6 anti-D6 background, and using this Green
function to obtain the fully back-reacted solution for a supertube with varying
charge density in this background. We show that this supertube can store
parametrically more entropy than in flat space, confirming the entropy
enhancement mechanism that was predicted using brane probes. We also show that
all the local properties of the fully back-reacted solution can, in fact, be
obtained using the DBI action of an appropriate brane probe. In particular, the
supergravity and the DBI analysis yield identical functional bubble equations
that govern the relative locations of the centers. This indicates that there is
a non-renormalization theorem that protects these functional equations as one
moves in moduli space. Our construction creates configurations that are beyond
the scope of recent arguments that appear to put strong limits on the entropy
that can be found in smooth supergravity solutions.Comment: 46 pages, 1 figure, LaTe
Eukaryotic Cells Producing Ribosomes Deficient in Rpl1 Are Hypersensitive to Defects in the Ubiquitin-Proteasome System
It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.United States. National Institutes of Health (GM25532)United States. National Institutes of Health (ARRAGM25532-S1)United States. National Institutes of Health (GM085177)United States. National Institutes of Health (CAI-3330)Natural Sciences and Engineering Research Council of Canada (NSERC
3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell
The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes
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