462 research outputs found
A mutate-and-map protocol for inferring base pairs in structured RNA
Chemical mapping is a widespread technique for structural analysis of nucleic
acids in which a molecule's reactivity to different probes is quantified at
single-nucleotide resolution and used to constrain structural modeling. This
experimental framework has been extensively revisited in the past decade with
new strategies for high-throughput read-outs, chemical modification, and rapid
data analysis. Recently, we have coupled the technique to high-throughput
mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure
of not only that nucleotide but also its interaction partner. Carrying out the
mutation and mapping for the entire system gives an experimental approximation
of the molecules contact map. Here, we give our in-house protocol for this
mutate-and-map strategy, based on 96-well capillary electrophoresis, and we
provide practical tips on interpreting the data to infer nucleic acid
structure.Comment: 22 pages, 5 figure
State-space Manifold and Rotating Black Holes
We study a class of fluctuating higher dimensional black hole configurations
obtained in string theory/ -theory compactifications. We explore the
intrinsic Riemannian geometric nature of Gaussian fluctuations arising from the
Hessian of the coarse graining entropy, defined over an ensemble of brane
microstates. It has been shown that the state-space geometry spanned by the set
of invariant parameters is non-degenerate, regular and has a negative scalar
curvature for the rotating Myers-Perry black holes, Kaluza-Klein black holes,
supersymmetric black holes, - configurations and the
associated BMPV black holes. Interestingly, these solutions demonstrate that
the principal components of the state-space metric tensor admit a positive
definite form, while the off diagonal components do not. Furthermore, the ratio
of diagonal components weakens relatively faster than the off diagonal
components, and thus they swiftly come into an equilibrium statistical
configuration. Novel aspects of the scaling property suggest that the
brane-brane statistical pair correlation functions divulge an asymmetric
nature, in comparison with the others. This approach indicates that all above
configurations are effectively attractive and stable, on an arbitrary
hyper-surface of the state-space manifolds. It is nevertheless noticed that
there exists an intriguing relationship between non-ideal inter-brane
statistical interactions and phase transitions. The ramifications thus
described are consistent with the existing picture of the microscopic CFTs. We
conclude with an extended discussion of the implications of this work for the
physics of black holes in string theory.Comment: 44 pages, Keywords: Rotating Black Holes; State-space Geometry;
Statistical Configurations, String Theory, M-Theory. PACS numbers: 04.70.-s
Physics of black holes; 04.70.Bw Classical black holes; 04.70.Dy Quantum
aspects of black holes, evaporation, thermodynamics; 04.50.Gh
Higher-dimensional black holes, black strings, and related objects. Edited
the bibliograph
EVH Black Holes, AdS3 Throats and EVH/CFT Proposal
Within class of generic black holes there are extremal black holes (with
vanishing Hawking temperature T) and vanishing horizon area Ah, but with finite
Ah/T ratio,the Extremal Vanishing Horizon (EVH) black holes. We study the near
horizon limit of a four dimensional EVH black hole solution to a generic
(gauged) Einstein-Maxwell dilaton theory and show that in the near horizon
limit they develop a throat which is a pinching orbifold limit of AdS3. This is
an extension of the well known result for extremal black holes the near horizon
limit of which contains an AdS2 throat. We show that in the near EVH near
horizon limit the pinching AdS3 factor turns to a pinching BTZ black hole and
that this near horizon limit is indeed a decoupling limit. We argue that the
pinching AdS3 or BTZ orbifold is resolved if the near horizon limit is
accompanied by taking the 4d Newton constant G4 to zero such that the
Bekenstein-Hawking entropy S = Ah/(4G4) remains finite. We propose that in this
limit the near horizon EVH black hole is dual to a 2d CFT. We provide pieces of
evidence in support of the EVH/CFT correspondence and comment on its connection
to the Kerr/CFT proposal and speculations how the EVH/CFT may be used to study
generic e.g. Schwarzchild-type black holes.Comment: 31 pages, 3 figures, JHEP styl
Logarithmic Corrections to Schwarzschild and Other Non-extremal Black Hole Entropy in Different Dimensions
Euclidean gravity method has been successful in computing logarithmic
corrections to extremal black hole entropy in terms of low energy data, and
gives results in perfect agreement with the microscopic results in string
theory. Motivated by this success we apply Euclidean gravity to compute
logarithmic corrections to the entropy of various non-extremal black holes in
different dimensions, taking special care of integration over the zero modes
and keeping track of the ensemble in which the computation is done. These
results provide strong constraint on any ultraviolet completion of the theory
if the latter is able to give an independent computation of the entropy of
non-extremal black holes from microscopic description. For Schwarzschild black
holes in four space-time dimensions the macroscopic result seems to disagree
with the existing result in loop quantum gravity.Comment: LaTeX, 40 pages; corrected small typos and added reference
Gravitational collapse and thermalization in the hard wall model
We study a simple example of holographic thermalization in a confining field
theory: the homogeneous injection of energy in the hard wall model. Working in
an amplitude expansion, we find black brane formation for sufficiently fast
energy injection and a scattering wave solution for sufficiently slow
injection. We comment on our expectations for more sophisticated holographic
QCD models.Comment: 33 pages, 5 figure
The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum
The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders
Surprisingly Simple Spectra
The large N limit of the anomalous dimensions of operators in
super Yang-Mills theory described by restricted Schur polynomials, are studied.
We focus on operators labeled by Young diagrams that have two columns (both
long) so that the classical dimension of these operators is O(N). At large N
these two column operators mix with each other but are decoupled from operators
with columns. The planar approximation does not capture the large N
dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator
is explicitly evaluated. In all three cases, in a certain limit, the dilatation
operator is a lattice version of a second derivative, with the lattice emerging
from the Young diagram itself. The one loop dilatation operator is diagonalized
numerically. All eigenvalues are an integer multiple of and there
are interesting degeneracies in the spectrum. The spectrum we obtain for the
one loop anomalous dimension operator is reproduced by a collection of harmonic
oscillators. This equivalence to harmonic oscillators generalizes giant
graviton results known for the BPS sector and further implies that the
Hamiltonian defined by the one loop large dilatation operator is
integrable. This is an example of an integrable dilatation operator, obtained
by summing both planar and non-planar diagrams.Comment: 34 page
ruvA Mutants that resolve Holliday junctions but do not reverse replication forks
RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination
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Tumour-infiltrated cortex participates in large-scale cognitive circuits.
The extent to which tumour-infiltrated brain tissue contributes to cognitive function remains unclear. We tested the hypothesis that cortical tissue infiltrated by diffuse gliomas participates in large-scale cognitive circuits using a unique combination of intracranial electrocorticography (ECoG) and resting-state functional magnetic resonance (fMRI) imaging in four patients. We also assessed the relationship between functional connectivity with tumour-infiltrated tissue and long-term cognitive outcomes in a larger, overlapping cohort of 17 patients. We observed significant task-related high gamma (70-250 Hz) power modulations in tumour-infiltrated cortex in response to increased cognitive effort (i.e., switch counting compared to simple counting), implying preserved functionality of neoplastic tissue for complex tasks probing executive function. We found that tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in executive function. Specifically, we discovered that tumour-infiltrated cortex with larger task-related high gamma power modulations tended to be more functionally connected to the dorsal attention network (DAN). Finally, we demonstrated that tumour-DAN connectivity is evident across a larger cohort of patients with gliomas and that it relates to long-term postsurgical outcomes in goal-directed attention. Overall, this study contributes convergent fMRI-ECoG evidence that tumour-infiltrated cortex participates in large-scale neurocognitive circuits that support executive function in health. These findings underscore the potential clinical utility of mapping large-scale connectivity of tumour-infiltrated tissue in the care of patients with diffuse gliomas
Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico
<p>Abstract</p> <p>Background</p> <p>Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.</p> <p>Methods</p> <p>We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity.</p> <p>Results</p> <p>The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAs<sup>III</sup>) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance.</p> <p>Conclusions</p> <p>Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAs<sup>III</sup>.</p
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