Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.

Intermediate conductance, calcium-activated potassium channels are gated by the binding of intracellular Ca(2+) to calmodulin, a Ca(2+)-binding protein that is constitutively associated with the C terminus of the channel. Although previous studies indicated that the pore-lining residues along the C-terminal portion of S6 contribute to the activation mechanism, little is known about whether the nonluminal face of S6 contributes to this process. Here we demonstrate that the sulfhydral reagent, parachloromercuribenze sulfonate (PCMBS), modifies an endogenous cysteine residue predicted to have a nonluminal orientation (Cys(276)) along the sixth transmembrane segment (S6). Modification of Cys(276) manipulates the steady-state and kinetic behavior of the channel by shifting the gating equilibrium toward the open state, resulting in a left shift in apparent Ca(2+) affinity and a slowing in the deactivation process. Using a six-state gating scheme, our analysis shows that PCMBS slows the transition between the open state back to the third closed state. Interpreting this result in the context of the steady-state and kinetic data suggests that PCMBS functions to shift the gating equilibrium toward the open state by disrupting channel closing. In an attempt to understand whether the nonluminal face of S6 participates in the activation mechanism, we conducted a partial tryptophan scan of this region. Substituting a tryptophan for Leu(281) recapitulated the effect on the steady-state and kinetic behavior observed with PCMBS. Considering the predicted nonluminal orientation of Cys(276) and Leu(281), a simple physical interpretation of these results is that the nonluminal face of S6 forms a critical interaction surface mediating the transition into the closed conformation, suggesting the nonluminal C-terminal portion of S6 is allosterically coupled to the activation gate

The Potential Impact of a Proposed Ban on the Sale of U.S. Horses for Slaughter and Human Consumption

Both federal and state governments in the United States are being asked to enact laws that would make slaughtering of horses for human consumption illegal. In the past, the United States was one of the principal exporters of horsemeat to Europe. This paper examines the impacts of a proposed ban on the U.S. horse industry and the U.S. export market for horsemeat. Findings indicate a loss of approximately $300 per horse in the United States as a result of such a ban. The supply of U.S. exported horsemeat has declined during the past decade. The results suggest that the most significant factors influencing this decline are lower real prices and competing imports.horse slaughter, horsemeat, meat exports, Agricultural and Food Policy, Livestock Production/Industries,

Do Economic Restrictions Improve Forecasts?

A previous study showed that imposing economic restrictions improves the forecasting ability of food demand systems, thus warranting their use even when rejected in-sample. This study attempts to determine whether this is due solely to the fact that restrictions improve degrees of freedom. Results indicate that restrictions improve forecasting ability even when not derived from economic theory, but theoretical restrictions forecast best.Demand and Price Analysis,

Do Economic Restrictions Improve Forecasts?

A previous study showed that imposing economic restrictions improves the forecasting ability of food demand systems, thus warranting their use even when rejected in-sample. This study attempts to determine whether this is due solely to the fact that restrictions improve degrees of freedom. Results indicate that restrictions improve forecasting ability even when not derived from economic theory, but theoretical restrictions forecast best.Demand and Price Analysis,

Design and characterization of a research electrohydraulic lithotripter patterned after the Dornier HM3

An electrohydraulic lithotripter has been designed that mimics the behavior of the Dornier HM3 extracorporeal shock wave lithotripter. The key mechanical and electrical properties of a clinical HM3 were measured and a design implemented to replicate these parameters. Three research lithotripters have been constructed on this design and are being used in a multi-institutional, multidisciplinary research program to determine the physical mechanisms of stone fragmentation and tissue damage in shock wave lithotripsy. The acoustic fields of the three research lithotripters and of two clinical Dornier HM3 lithotripters were measured with a PVDF membrane hydrophone. The peak positive pressure, peak negative pressure, pulse duration, and shock rise time of the focal waveforms were compared. Peak positive pressures varied from 25 MPa at a voltage setting of 12 kV to 40 MPa at 24 kV. The magnitude of the peak negative pressure varied from -7 to -12 MPa over the same voltage range. The spatial variations of the peak positive pressure and peak negative pressure were also compared. The focal region, as defined by the full width half maximum of the peak positive pressure, was 60 mm long in the axial direction and 10 mm wide in the lateral direction. The performance of the research lithotripters was found to be consistent at clinical firing rates (up to 3 Hz). The results indicated that pressure fields in the research lithotripters are equivalent to those generated by a clinical HM3 lithotripter

Regulation of pancreatic cancer aggressiveness by stromal stiffening

No abstract available

Pharmacological activation of the nuclear receptor REV-ERB reverses cognitive deficits and reduces amyloid-β burden in a mouse model of Alzheimer’s disease

Alzheimer’s disease currently lacks treatment options that effectively reverse the biological/anatomical pathology and cognitive deficits associated with the disease. Loss of function of the nuclear receptor REV-ERB is associated with reduced cognitive function in mouse models. The effect of enhanced REV-ERB activity on cognitive function has not been examined. In this study, we tested the hypothesis that enhanced REV-ERB function may enhance cognitive function in a model of Alzheimer’s disease. We utilized the REV-ERB agonist SR9009 to pharmacologically activate the activity of REV-ERB in the SAMP8 mouse model of Alzheimer’s disease. SR9009 reversed cognitive dysfunction of an aged SAMP8 mouse in several behavioral assays including novel object recognition, T-maze foot shock avoidance, and lever press operant conditioning task assessments. SR9009 treatment reduced amyloid-β 1–40 and 1–42 levels in the cortex, which is consistent with improved cognitive function. Furthermore, SR9009 treatment led to increased hippocampal PSD-95, cortical synaptophysin expression and the number of synapses suggesting improvement in synaptic function. We conclude that REV-ERB is a potential target for treatment of Alzheimer’s disease.</div

Laboratory Measurements Of White Dwarf Photospheric Spectral Lines: H Beta

We spectroscopically measure multiple hydrogen Balmer line profiles from laboratory plasmas to investigate the theoretical line profiles used in white dwarf (WD) atmosphere models. X-ray radiation produced at the Z Pulsed Power Facility at Sandia National Laboratories initiates plasma formation in a hydrogen-filled gas cell, replicating WD photospheric conditions. Here we present time-resolved measurements of H beta and fit this line using different theoretical line profiles to diagnose electron density, n(e), and n = 2 level population, n2. Aided by synthetic tests, we characterize the validity of our diagnostic method for this experimental platform. During a single experiment, we infer a continuous range of electron densities increasing from n(e) similar to 4 to similar to 30 x 10(16) cm(-3) throughout a 120-ns evolution of our plasma. Also, we observe n(2) to be initially elevated with respect to local thermodynamic equilibrium (LTE); it then equilibrates within similar to 55 ns to become consistent with LTE. This supports our electrontemperature determination of T-e similar to 1.3 eV (similar to 15,000 K) after this time. At n(e) greater than or similar to 10(17) cm(-3), we find that computer-simulation-based line-profile calculations provide better fits (lower reduced chi(2)) than the line profiles currently used in the WD astronomy community. The inferred conditions, however, are in good quantitative agreement. This work establishes an experimental foundation for the future investigation of relative shapes and strengths between different hydrogen Balmer lines.Laboratory Directed Research and Development programUnited States Department of Energy DE-AC04-94AL85000, DE-SC0010623National Science Foundation DGE-1110007Astronom

Sport and Family Functioning: Strengthening Elite Sport Families

Families play an important role in society, both in human sustenance and individual development.  Family systems theory views the family as a series of interconnected parts that when functioning properly, provide individual members with multiple benefits. Interaction with external systems, such as sport, school or church, can have positive and negative impacts on the family. It is unclear, however, what elements of sport relate to specific outcomes.  The purpose of this study is to better understand the relationship between elite youth sport participation and family units, and how these two spheres, individually and in combination, impact family functioning.  In-depth, purposeful interviews with seven “sport families” revealed that in addition to the depletion of resources (financial and time), elite sport engagement strongly detracts from the marital dyad and family unit receiving sufficient time and attention for proper functioning.  The results also offer insight into how the leagues can be better managed such that they positively contribute to family functioning.  Specifically, the results indicate that leagues can aid in strengthening family functioning through allowing families to have coaching input, and providing greater attention to scheduling, league expectations, and instrumental support

Implementation of the Combined--Nonlinear Condensation Transformation

We discuss several applications of the recently proposed combined nonlinear-condensation transformation (CNCT) for the evaluation of slowly convergent, nonalternating series. These include certain statistical distributions which are of importance in linguistics, statistical-mechanics theory, and biophysics (statistical analysis of DNA sequences). We also discuss applications of the transformation in experimental mathematics, and we briefly expand on further applications in theoretical physics. Finally, we discuss a related Mathematica program for the computation of Lerch's transcendent.Comment: 23 pages, 1 table, 1 figure (Comput. Phys. Commun., in press