695 research outputs found
Modeling DNA beacons at the mesoscopic scale
We report model calculations on DNA single strands which describe the
equilibrium dynamics and kinetics of hairpin formation and melting. Modeling is
at the level of single bases. Strand rigidity is described in terms of simple
polymer models; alternative calculations performed using the freely rotating
chain and the discrete Kratky-Porod models are reported. Stem formation is
modeled according to the Peyrard-Bishop-Dauxois Hamiltonian. The kinetics of
opening and closing is described in terms of a diffusion-controlled motion in
an effective free energy landscape. Melting profiles, dependence of melting
temperature on loop length, and kinetic time scales are in semiquantitative
agreement with experimental data obtained from fluorescent DNA beacons forming
poly(T) loops. Variation in strand rigidity is not sufficient to account for
the large activation enthalpy of closing and the strong loop length dependence
observed in hairpins forming poly(A) loops. Implications for modeling single
strands of DNA or RNA are discussed.Comment: 15 pages, 17 figures, submitted to Eur. J. Phys.
A new bond fluctuation method for a polymer undergoing gel electrophoresis
We present a new computational methodology for the investigation of gel
electrophoresis of polyelectrolytes. We have developed the method initially to
incorporate sliding motion of tight parts of a polymer pulled by an electric
field into the bond fluctuation method (BFM). Such motion due to tensile force
over distances much larger than the persistent length is realized by non-local
movement of a slack monomer at an either end of the tight part. The latter
movement is introduced stochastically. This new BFM overcomes the well-known
difficulty in the conventional BFM that polymers are trapped by gel fibers in
relatively large fields. At the same time it also reproduces properly
equilibrium properties of a polymer in a vanishing filed limit. The new BFM
thus turns out an efficient computational method to study gel electrophoresis
in a wide range of the electric field strength.Comment: 15 pages, 11 figure
S6K1 and 4E-BP1 Are Independent Regulated and Control Cellular Growth in Bladder Cancer
Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and the mitogen activated protein kinase (MAPK) signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC). However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK
Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag
We study the electrophoretic separation of polyelectrolytes of varying
lengths by means of end-labeled free-solution electrophoresis (ELFSE). A
coarse-grained molecular dynamics simulation model, using full electrostatic
interactions and a mesoscopic Lattice Boltzmann fluid to account for
hydrodynamic interactions, is used to characterize the drag coefficients of
different label types: linear and branched polymeric labels, as well as
transiently bound micelles.
It is specifically shown that the label's drag coefficient is determined by
its hydrodynamic size, and that the drag per label monomer is largest for
linear labels. However, the addition of side chains to a linear label offers
the possibility to increase the hydrodynamic size, and therefore the label
efficiency, without having to increase the linear length of the label, thereby
simplifying synthesis. The third class of labels investigated, transiently
bound micelles, seems very promising for the usage in ELFSE, as they provide a
significant higher hydrodynamic drag than the other label types.
The results are compared to theoretical predictions, and we investigate how
the efficiency of the ELFSE method can be improved by using smartly designed
drag-tags.Comment: 32 pages, 11 figures, submitted to Macromolecule
A novel role for microglia in minimizing excitotoxicity
Microglia are the abundant, resident myeloid cells of the central nervous system (CNS) that become rapidly activated in response to injury or inflammation. While most studies of microglia focus on this phenomenon, little is known about the function of 'resting' microglia, which possess fine, branching cellular processes. Biber and colleagues, in a recent paper in Journal of Neuroinflammation, report that ramified microglia can limit excitotoxicity, an important insight for understanding mechanisms that limit neuron death in CNS disease
Development of a heme protein structure–electrochemical function database
Proteins containing heme, iron(protoporphyrin IX) and its variants, continue to be one of the most-studied classes of biomolecules due to their diverse range of biological functions. The literature is abundant with reports of structural and functional characterization of individual heme proteins which demonstrate that heme protein reduction potential values, Em, span the range from –550 mV to +450 mV versus SHE. In order to unite these data for the purposes of global analysis, a new web-based resource of heme protein structure–function relationships is presented: the Heme Protein Database (HPD). This database is the first of its kind to combine heme protein structural classifications including protein fold, heme type and heme axial ligands, with heme protein reduction potential values in a web-searchable format. The HPD is located at http://heme.chem.columbia.edu/heme.php. The data illustrate that heme protein Em values are modulated over a 300 mV range by the type of global protein fold, a 600 mV range by the type of porphyrin and an 800 mV range by the axial ligands. Thus, the 1 V range observed in heme protein reduction potential values in biological systems arises from subtle combinations of these various factors
The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
Peer reviewedPublisher PD
The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time
Peer reviewedPreprin
Demographic survey of pediatric patients presenting to a chiropractic teaching clinic
<p>Abstract</p> <p>Background</p> <p>Considering the increasing use of alternative therapies for children, it is appropriate to determine the demographic profile of pediatric patients entering a chiropractic clinic.</p> <p>Methods</p> <p>Collection of demographic data including age, gender, condition at presentation, previous clinicians consulted and medical referral rates of pediatric patients presenting to a chiropractic teaching clinic between 2006 and 2010.</p> <p>Results</p> <p>Over-all, 20.5% of patients were aged between two days and 15 years and classified as pediatric patients. The most common presenting complaint was musculoskeletal (35%). Excess crying (30%) was the most common complaint in the largest presenting age group which was under 12 weeks of age (62.3%). All children had previously presented for medical care for the same condition. Most (83%) of the infant patients under 12 weeks of age were referred for care by a medical practitioner.</p> <p>Conclusion</p> <p>Parents commonly presented their child for care at this chiropractic clinic with a recommendation from a medical practitioner. The most common complaints were musculoskeletal and excessive crying conditions and the most prevalent age group was under 12 weeks of age.</p
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