79 research outputs found
Driven lattice gases: models for intracellular transport
Intracellular transport phenomena, such as kinesins and myosins moving
along cytoskeletal filaments or ribosomes along messenger RNA, can be
modeled by one-dimensional driven lattice gases. Among these, the
Totally Asymmetric Simple Exclusion Process (TASEP), has been
extensively used. It describes a system of particles hopping in a
preferred direction with hard core interaction. The goal of this
thesis is to explore the relevance of some features that are missed by
this simple model, such as the exchange of particles between molecular
track and the cytoplasm, the extended molecular structure of each
motor, and the interaction of motors with imperfections on the track
acting as road blocks for intracellular traffic.
Recent studies have taken into account particle exchange between the
track and bulk solution (Langmuir kinetics). It was found that this
violation of current conservation along the track leads to phase
coexistence regions in the phase diagram not present in the TASEP. We
have extended these studies in two ways. First, motivated by the fact
that many molecular motors are dimers, we study how the stationary
properties of the system (density profile and phase behavior) change
upon replacing monomers with extended particles. Analytical refined
and generalized mean field theory, supported by numerical Monte Carlo
simulations, give a detailed description of the phase diagram. Our
study proves that the extension gives quantitative but not qualitative
changes in the phase diagram, showing that the picture obtained in the
case of monomers is robust upon considering extended particles.
Second, motivated by the presence of structural imperfections of the
track that act as road blocks, we study the influence of an isolated
defect characterized by a reduced hopping rate on the non-equilibrium
steady state. We explore the phase behavior in the full parameter
range and find that the phase diagram changes qualitatively as
compared to the case without defects, showing new phase coexistence
regions. In particular above a certain threshold strength of the
defect, its presence induces a macroscopic change in the density
profile. The regions where the defect is relevant (called bottleneck
phases) are identified and studied.
In the second part of the thesis we investigate the dynamical features
of these models. First we concentrate on the dynamics of the simple
TASEP, for which a complete analysis was missing. We use a technique
borrowed from solid state physics, the Boltzmann-Langevin method, to
give a full description of the correlation function in the whole
parameter space. Finally we study the dynamics of a tracer particle
in a TASEP with on-off kinetics. We observe that it is possible to
reconstruct the density profile from the velocity of the tracer
particle and we propose to perform single molecule experiments with
fluorescently labelled molecular motors to explore the density profile
and ultimately test the phase behavior predicted in this thesis
Tell Barri / Kahat. La campagna del 2003
In the undulating plains of north-eastern Syria is the site of Tell Barri, identified with the city of Kahat. The archaeological sequence which has been brought to light stretches without interruption from the start of the third millennium up to the fourteenth century AD. This report illustrates the results of the twentieth excavation campaign, carried out by the group from the University of Florence and from the "Federico II" University of Naples. In Area G, the excavation of the chapel dating to the third millennium proceeded along with that of the palace of the Mid Assyrian King Adadnirari I; three coeval tombs were discovered, two with lavish furnishings. In Area J, the exploration of the Assyrian palace of Tukulti-Ninurta II was continued. As regards the Parthian phase, investigation has proceeded on the Great Defensive Wall in Area E and of the residential section in Area H. The text, prepared for printing in July 2005, was published following the tragic death of Paolo Emilio Pecorella, which took place on 29 August in Tell Barri in the course of the excavation campaign
Tell Barri / Kahat. La campagna del 2004
In the undulating plains of north-eastern Syria is the site of Tell Barri, identified with the city of Kahat. The archaeological sequence which has been brought to light stretches without interruption from the start of the third millennium up to the fourteenth century AD. This report illustrates the results of the twentieth excavation campaign, carried out by the group from the University of Florence and from the "Federico II" University of Naples. In Area G the levels of the first half of the III millennium BC and a sequence of strata of the Mitanni epoch were investigated, while on the western border of the site another section of the palace of Adad-nirari I was brought to light. In Area J the operations exposed the eastward extension of the palace structure resulting from transformations in the Neo-Babylonian period; in the northern section another courtyard of the palace of Tukulti Ninurta II was brought to light. The text, prepared for printing in July 2005, was published following the tragic death of Paolo Emilio Pecorella, which took place on 29 August in Tell Barri in the course of the excavation campaign
Dynamic correlation functions and Boltzmann Langevin approach for driven one dimensional lattice gas
We study the dynamics of the totally asymmetric exclusion process with open
boundaries by phenomenological theories complemented by extensive Monte-Carlo
simulations. Upon combining domain wall theory with a kinetic approach known as
Boltzmann-Langevin theory we are able to give a complete qualitative picture of
the dynamics in the low and high density regime and at the corresponding phase
boundary. At the coexistence line between high and low density phases we
observe a time scale separation between local density fluctuations and
collective domain wall motion, which are well accounted for by the
Boltzmann-Langevin and domain wall theory, respectively. We present Monte-Carlo
data for the correlation functions and power spectra in the full parameter
range of the model.Comment: 10 pages, 9 figure
Bottleneck-induced transitions in a minimal model for intracellular transport
We consider the influence of disorder on the non-equilibrium steady state of
a minimal model for intracellular transport. In this model particles move
unidirectionally according to the \emph{totally asymmetric exclusion process}
(TASEP) and are coupled to a bulk reservoir by \emph{Langmuir kinetics}. Our
discussion focuses on localized point defects acting as a bottleneck for the
particle transport. Combining analytic methods and numerical simulations, we
identify a rich phase behavior as a function of the defect strength. Our
analytical approach relies on an effective mean-field theory obtained by
splitting the lattice into two subsystems, which are effectively connected
exploiting the local current conservation. Introducing the key concept of a
carrying capacity, the maximal current which can flow through the bulk of the
system (including the defect), we discriminate between the cases where the
defect is irrelevant and those where it acts as a bottleneck and induces
various novel phases (called {\it bottleneck phases}). Contrary to the simple
TASEP in the presence of inhomogeneities, many scenarios emerge and translate
into rich underlying phase-diagrams, the topological properties of which are
discussed.Comment: 14 pages, 15 figures, 1 tabl
Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast
BACKGROUND: Sentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial. The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS. METHODS: A retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004. Subdermal or subareolar injection of 30â50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin. RESULTS: Only one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found. CONCLUSION: Our findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible
EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription
Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress
Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension.
Membrane fusion underlies multiple processes, including exocytosis of hormones and neurotransmitters. Membrane fusion starts with the formation of a narrow fusion pore. Radial expansion of this pore completes the process and allows fast release of secretory compounds, but this step remains poorly understood. Here we show that inhibiting the expression of the small GTPase Cdc42 or preventing its activation with a dominant negative Cdc42 construct in human neuroendocrine cells impaired the release process by compromising fusion pore enlargement. Consequently the mode of vesicle exocytosis was shifted from full-collapse fusion to kiss-and-run. Remarkably, Cdc42-knockdown cells showed reduced membrane tension, and the artificial increase of membrane tension restored fusion pore enlargement. Moreover, inhibiting the motor protein myosin II by blebbistatin decreased membrane tension, as well as fusion pore dilation. We conclude that membrane tension is the driving force for fusion pore dilation and that Cdc42 is a key regulator of this force.journal articleresearch support, non-u.s. gov't2014 Oct 152014 08 20importe
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