8,774 research outputs found
Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades
Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution
A Test of the Adaptive Market Hypothesis using a Time-Varying AR Model in Japan
This study examines the adaptive market hypothesis (AMH) in Japanese stock
markets (TOPIX and TSE2). In particular, we measure the degree of market
efficiency by using a time-varying model approach. The empirical results show
that (1) the degree of market efficiency changes over time in the two markets,
(2) the level of market efficiency of the TSE2 is lower than that of the TOPIX
in most periods, and (3) the market efficiency of the TOPIX has evolved, but
that of the TSE2 has not. We conclude that the results support the AMH for the
more qualified stock market in Japan.Comment: 10 pages, 2 figure, 2 table
Critical behavior in colloid-polymer mixtures: theory and simulation
We extensively investigated the critical behavior of mixtures of colloids and
polymers via the two-component Asakura-Oosawa model and its reduction to a
one-component colloidal fluid using accurate theoretical and simulation
techniques. In particular the theoretical approach, hierarchical reference
theory [Adv. Phys. 44, 211 (1995)], incorporates realistically the effects of
long-range fluctuations on phase separation giving exponents which differ
strongly from their mean-field values, and are in good agreement with those of
the three-dimensional Ising model. Computer simulations combined with
finite-size scaling analysis confirm the Ising universality and the accuracy of
the theory, although some discrepancy in the location of the critical point
between one-component and full-mixture description remains. To assess the limit
of the pair-interaction description, we compare one-component and two-component
results.Comment: 15 pages, 10 figures. Submitted to Phys. Rev.
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Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques.
Herpes simplex virus 2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study host-HSV-2 interactions, an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333, and/or G) at a total dose of 1 × 107 PFU of HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA were consistently shed in vaginal swabs for the first 7 to 14 days after each inoculation. Proteins associated with wound healing, innate immunity, and inflammation were significantly increased in cervical secretions immediately after HSV-2 inoculation. There was histologic evidence of acute herpesvirus pathology, including acantholysis in the squamous epithelium and ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen in mucosal epithelial cells and keratinocytes. Further, an intense inflammatory infiltrate was found in the cervix and vulva. Evidence of latent infection and reactivation was demonstrated by the detection of spontaneous HSV-2 shedding post-acute inoculation (102 to 103 DNA copies/swab) in 80% of RM. Further, HSV-2 DNA was detected in ganglia in most necropsied animals. HSV-2-specifc T-cell responses were detected in all animals, although antibodies to HSV-2 were detected in only 30% of the animals. Thus, HSV-2 infection of RM recapitulates many of the key features of subclinical HSV-2 infection in women but seems to be more limited, as virus shedding was undetectable more than 40 days after the last virus inoculation.IMPORTANCE Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study of the initial molecular interactions of the two agents requires an animal model. We found that HSV-2 can infect RM after vaginal inoculation, establish latency in the nervous system, and spontaneously reactivate; these features mimic some of the key features of HSV-2 infection in women. RM may provide an animal model to develop strategies to prevent HSV-2 acquisition and reactivation
Expression, refolding and spectroscopic characterization of fibronectin type III (FnIII)-homology domains derived from human fibronectin leucine rich transmembrane protein (FLRT)-1,-2, and-3
The fibronectin leucine rich transmembrane (FLRT) protein family consists in humans of 3 proteins, FLRT1, -2, and -3. The FLRT proteins contain two extracellular domains separated by an unstructured linker. The most membrane distal part is a leucine rich repeat (LRR) domain responsible for both cis- and trans-interactions, whereas the membrane proximal part is a fibronectin type III (FnIII) domain responsible for a cis-interaction with members of the fibroblast growth factor receptor 1 (FGFR1) family, which results in FGFR tyrosine kinase activation. Whereas the structures of FLRT LRR domains from various species have been determined, the expression and purification of recombinant FLRT FnIII domains, important steps for further structural and functional characterizations of the proteins, have not yet been described. Here we present a protocol for expressing recombinant FLRT-FnIII domains in inclusion bodies in Escherichia coli. His-tags permitted affinity purification of the domains, which subsequently were refolded on a Ni-NTA agarose column by reducing the concentration of urea. The refolding was confirmed by circular dichroism (CD) and 1H-NMR. By thermal unfolding experiments we show that a strand-strand cystine bridge has significant effect on the stability of the FLRT FnIII fold. We further show by Surface Plasmon Resonance that all three FnIII domains bind to FGFR1, and roughly estimate a Kd for each domain, all Kds being in the µM range
Star polymers: A study of the structural arrest in presence of attractive interactions
Simulations and Mode-Coupling Theory calculations, for a large range of the
arm number and packing fraction have shown that the structural
arrest and the dynamics of star polymers in a good solvent are extremely rich:
the systems show a reentrant melting of the disordered glass nested between two
stable fluid phases that strongly resemble the equilibrium phase diagram.
Starting from a simple model potential we investigate the effect of the
interplay between attractive interactions of different range and ultrasoft core
repulsion, on the dynamics and on the occurrence of the ideal glass transition
line. In the two cases considered so far, we observed some significant
differences with respect to the purely repulsive pair interaction. We also
discuss the interplay between equilibrium and non equilibrium phase behavior.
The accuracy of the theoretical tools we utilized in our investigation has been
checked by comparing the results with molecular dynamics simulations.Comment: 24 pages, 14 figures, accepted for publication in Physical Review
How cold is Dark Matter? Constraints from Milky Way Satellites
We test the luminosity function of Milky Way satellites as a constraint for
the nature of Dark Matter particles. We perform dissipationless high-resolution
N-body simulations of the evolution of Galaxy-sized halo in the standard Cold
Dark Matter (CDM) model and in four Warm Dark Matter (WDM) scenarios, with a
different choice for the WDM particle mass (m_w). We then combine the results
of the numerical simulations with semi-analytic models for galaxy formation, to
infer the properties of the satellite population. Quite surprisingly we find
that even WDM models with relatively low m_w values (2-5 keV) are able to
reproduce the observed abundance of ultra faint (Mv<-9) dwarf galaxies, as well
as the observed relation between Luminosity and mass within 300 pc. Our results
suggest a lower limit of 1 keV for thermal warm dark matter, in broad agreement
with previous results from other astrophysical observations like Lyman-alpha
forest and gravitational lensing.Comment: 6 pages, 5 figures. Introduction improved, references added. Accepted
for publication on MNRAS Letter
Bias in Estimating Multivariate and Univariate Diffusions
Published in Journal of Econometrics, 2011, https://doi.org/10.1016/j.jeconom.2010.12.006</p
Fluid-fluid demixing transitions in colloid--polyelectrolyte star mixtures
We derive effective interaction potentials between hard, spherical colloidal
particles and star-branched polyelectrolytes of various functionalities and
smaller size than the colloids. The effective interactions are based on a
Derjaguin-like approximation, which is based on previously derived potentials
acting between polyelectrolyte stars and planar walls. On the basis of these
interactions we subsequently calculate the demixing binodals of the binary
colloid--polyelectrolyte star mixture, employing standard tools from
liquid-state theory. We find that the mixture is indeed unstable at moderately
high overall concentrations. The system becomes more unstable with respect to
demixing as the star functionality and the size ratio grow.Comment: 24 pages, 9 figures, submitted to Journal of Physics: Condensed
Matte
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