Two-State Migration of DNA in a structured Microchannel

DNA migration in topologically structured microchannels with periodic cavities is investigated experimentally and with Brownian dynamics simulations of a simple bead-spring model. The results are in very good agreement with one another. In particular, the experimentally observed migration order of Lambda- and T2-DNA molecules is reproduced by the simulations. The simulation data indicate that the mobility may depend on the chain length in a nonmonotonic way at high electric fields. This is found to be the signature of a nonequilibrium phase transition between two different migration states, a slow one and a fast one, which can also be observed experimentally under appropriate conditions.Comment: Revised edition corresponding to the comments by the referees, submitted to Physical Review

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

Neuronal pentraxins mediate synaptic refinement in the developing visual system

Peer reviewedPublisher PD

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

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

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

Infrared Multiple Photon Dissociation Action Spectroscopy and Theoretical Studies of Diethyl Phosphate Complexes: Effects of Protonation and Sodium Cationization on Structure

The gas-phase structures of deprotonated, protonated, and sodium-cationized complexes of diethyl phosphate (DEP) including [DEP − H]−, [DEP + H]+, [DEP + Na]+, and [DEP − H + 2Na]+ are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy using tunable IR radiation generated by a free electron laser, a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) with an electrospray ionization (ESI) source, and theoretical electronic structure calculations. Measured IRMPD spectra are compared to linear IR spectra calculated at the B3LYP/6-31G(d,p) level of theory to identify the structures accessed in the experimental studies. For comparison, theoretical studies of neutral complexes are also performed. These experiments and calculations suggest that specific geometric changes occur upon the binding of protons and/or sodium cations, including changes correlating to nucleic acid backbone geometry, specifically P–O bond lengths and ∠OPO bond angles. Information from these observations may be used to gain insight into the structures of more complex systems, such as nucleotides and solvated nucleic acids

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

Glial Tumor Necrosis Factor Alpha (TNFα) Generates Metaplastic Inhibition of Spinal Learning

Injury-induced overexpression of tumor necrosis factor alpha (TNFα) in the spinal cord can induce chronic neuroinflammation and excitotoxicity that ultimately undermines functional recovery. Here we investigate how TNFα might also act to upset spinal function by modulating spinal plasticity. Using a model of instrumental learning in the injured spinal cord, we have previously shown that peripheral intermittent stimulation can produce a plastic change in spinal plasticity (metaplasticity), resulting in the prolonged inhibition of spinal learning. We hypothesized that spinal metaplasticity may be mediated by TNFα. We found that intermittent stimulation increased protein levels in the spinal cord. Using intrathecal pharmacological manipulations, we showed TNFα to be both necessary and sufficient for the long-term inhibition of a spinal instrumental learning task. These effects were found to be dependent on glial production of TNFα and involved downstream alterations in calcium-permeable AMPA receptors. These findings suggest a crucial role for glial TNFα in undermining spinal learning, and demonstrate the therapeutic potential of inhibiting TNFα activity to rescue and restore adaptive spinal plasticity to the injured spinal cord. TNFα modulation represents a novel therapeutic target for improving rehabilitation after spinal cord injury