238 research outputs found
Stochastic model for nucleosome sliding in the presence of DNA ligands
Heat-induced mobility of nucleosomes along DNA is an experimentally
well-studied phenomenon. A recent experiment shows that the repositioning is
modified in the presence of minor-groove binding DNA ligands. We present here a
stochastic three-state model for the diffusion of a nucleosome along DNA in the
presence of such ligands. It allows us to describe the dynamics and the steady
state of such a motion analytically. The analytical results are in excellent
agreement with numerical simulations of this stochastic process.With this
model, we study the response of a nucleosome to an external force and how it is
affected by the presence of ligands.Comment: 10 pages, 8 figures, submitted to Eur. Phys. J.
Footprint traversal by ATP-dependent chromatin remodeler motor
ATP-dependent chromatin remodeling enzymes (CRE) are bio-molecular motors in
eukaryotic cells. These are driven by a chemical fuel, namely, adenosine
triphosphate (ATP). CREs actively participate in many cellular processes that
require accessibility of specific segments of DNA which are packaged as
chromatin. The basic unit of chromatin is a nucleosome where 146 bp 50
nm of a double stranded DNA (dsDNA) is wrapped around a spool formed by histone
proteins. The helical path of histone-DNA contact on a nucleosome is also
called "footprint". We investigate the mechanism of footprint traversal by a
CRE that translocates along the dsDNA. Our two-state model of a CRE captures
effectively two distinct chemical (or conformational) states in the
mechano-chemical cycle of each ATP-dependent CRE. We calculate the mean time of
traversal. Our predictions on the ATP-dependence of the mean traversal time can
be tested by carrying out {\it in-vitro} experiments on mono-nucleosomes.Comment: 11 pages, 12 figures; minor revision of tex
Polymer reptation and nucleosome repositioning
We consider how beads can diffuse along a chain that wraps them, without
becoming displaced from the chain; our proposed mechanism is analogous to the
reptation of "stored length" in more familiar situations of polymer dynamics.
The problem arises in the case of globular aggregates of proteins (histones)
that are wound by DNA in the chromosomes of plants and animals; these beads
(nucleosomes) are multiply wrapped and yet are able to reposition themselves
over long distances, while remaining bound by the DNA chain.Comment: 9 pages, including 2 figures, to be published in Phys. Rev. Let
Noether theorem for mu-symmetries
We give a version of Noether theorem adapted to the framework of
mu-symmetries; this extends to such case recent work by Muriel, Romero and
Olver in the framework of lambda-symmetries, and connects mu-symmetries of a
Lagrangian to a suitably modified conservation law. In some cases this
"mu-conservation law'' actually reduces to a standard one; we also note a
relation between mu-symmetries and conditional invariants. We also consider the
case where the variational principle is itself formulated as requiring
vanishing variation under mu-prolonged variation fields, leading to modified
Euler-Lagrange equations. In this setting mu-symmetries of the Lagrangian
correspond to standard conservation laws as in the standard Noether theorem. We
finally propose some applications and examples.Comment: 28 pages, to appear in J. Phys.
Spontaneous life-threatening hemobilia during acute liver failure successfully treated with transarterial embolization
A 28-year-old patient admitted with jaundice, vomiting and deteriorating coagulopathy was diagnosed with acute liver failure. After listing for urgent transplantation, he developed Boerhaave’s syndrome and massive hemobilia, two life-threatening complications. Massive hemobilia secondary to a fistula between the right hepatic artery and the right bile duct occurred several days after transjugular biopsy and was controlled with fluid resuscitation, transfusion and arterial embolization. Two days later he was transplanted successfully, and is currently doing well after more than 72 months. Aggressive treatment of potentially reversible complications during acute liver failure whilst awaiting transplantation is mandatory to allow survival of these patients
Drivers and impact of antifungal therapy in critically ill patients with Aspergillus-positive respiratory tract cultures
Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P 7) (68.4% vs. 36.9%) (both P < 0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89–2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure
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