Contribution of electrostatic and structural properties of Kv4.3 S4 arginine residues to the regulation of channel gating

AbstractPrevious work has demonstrated that replacing individual arginine (R) residues in the S4 domain of Kv4.3 with alanine (A) not only altered activation and deactivation processes, but also those of closed-state inactivation (CSI) and recovery. R → A mutants eliminated individual positive charge while substantially reducing side chain volume and hydrophilic character. Their novel effects on gating may thus have been the result of electrostatic and/or structural perturbations. To address this issue, and to gain further insights into the roles that S4 plays in the regulation of Kv4.3 gating transitions, we comparatively analyzed arginine to glutamine (R → Q) mutations at positions 290, 293, and 296. This maneuver maintained positive charge elimination of the R → A mutants, while partially restoring native side chain volume and hydrophilic properties. R → A and R → Q mutant pairs produced similar effects on the forward gating process of activation. In contrast, significant differences between the two substitutions were discovered on deactivation, CSI, and recovery, with the R → Q mutants partially restoring wild type characteristics. Our results argue that modification of individual S4 residue properties may result in altered localized interactions within unique microenvironments encountered during forward and reverse gating transitions. As such, predominant effects appear on the reverse gating transitions of deactivation and recovery. These results are consistent with the proposal that arginine residues in S4 are involved in regulating Kv4.3 CSI and recovery

A Clinical Prediction Score to Guide Referral of Elderly Dialysis Patients for Kidney Transplant Evaluation.

IntroductionDialysis patients aged ≥70 years derive improved life expectancy through kidney transplantation compared to their waitlisted counterparts, but guidelines are not clear about how to identify appropriate transplantation candidates. We developed a clinical prediction score to identify elderly dialysis patients with expected 5-year survival appropriate for kidney transplantation (>5 years).MethodsIncident dialysis patients in 2006-2009 aged ≥70 were identified from the United States Renal Data System database and divided into derivation and validation cohorts. Using the derivation cohort, candidate variables with a significant crude association with 5-year all-cause mortality were included in a multivariable logistic regression model to generate a scoring system. The scoring system was tested in the validation cohort and a cohort of elderly transplant recipients.ResultsCharacteristics most predictive of 5-year mortality included age >80, body mass index (BMI) <18, the presence of congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), immobility, and being institutionalized. Factors associated with increased 5-year survival were non-white race, a primary cause of end stage renal disease (ESRD) other than diabetes, employment within 6 months of dialysis initiation, and dialysis start via arteriovenous fistula (AVF). 5-year mortality was 47% for the lowest risk score group (3.6% of the validation cohort) and >90% for the highest risk cohort (42% of the validation cohort).ConclusionThis clinical prediction score could be useful for physicians to identify potentially suitable candidates for kidney transplantation

The Arts and Sciences Face the Eighties: Beyond the Boundaries of Our Disciplines

Three Syracuse University faculty members discuss the academic mission on the occasion of the installation of Gershon Vincow as dean of the College of Arts and Sciences. Page 65

Alice in recidivism land: The Queens logic and child protection workers\u27 assessment of sexual dangerousness

This article is based on a case that highlights the dearth of cogent and pertinent risk assessment information in the reports and testimonies of many involved in assessing risks to children in real life problematic circumstances. In the case, the decision to exclude an intrafamilial sexual offender from the family home was made in large measure on the basis that the offender\u27s wife accepted the offender\u27s "denial of guilt" to accusations previously made against him. Keeping families apart should not be entertained without reliable and valid evidence pointing to that decision. However, as will be seen, the evidence often relied upon by child protection workers, albeit in good faith, is neither. The assessment processes described in the case point directly to what appears to be a wider lack of knowledge specific to assessment of recidivism, to misrepresentation of risk assessment information, and to overarching epistemological issues that appear to be widely ignored and/or misunderstood within the overall field of risk assessment and threat management. The purpose of this article is to describe how the information used to decide upon exclusion in the case cannot be considered probative and to iterate the methodological processes that must be considered in such cases if miscarriages of justice are to be avoided

Upper cenozoic chronostratigraphy of the southwestern Amazon Basin

The lack of numerical age dates for upper Cenozoic strata of the Amazon Basin has prevented resolution of its geologic history and accurate dating of important paleofaunas. Here we present results of magnetostratigraphy and 40Ar/39Ar dating of two volcanic ash deposits from the Madre de Dios Formation of eastern Peru. The two ash ages, 9.01 ± 0.28 Ma and 3.12 ± 0.02 Ma, provide the first numerical age data necessary for accurate interpretation of late Tertiary sedimentation in Amazonia and establish approximate time constraints for the last major cycle of Cenozoic deposition within the southwestern Amazon Basin. The older ash age also provides a minimum age for numerous Amazonian paleofaunas, which allows a more definitive correlation of these paleofaunas with those in other regions of South America

Role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Modulating Vascular Smooth Muscle Cells by Activating Large-Conductance Potassium Ion Channels

International audienceIn this chapter we propose to discuss the role of K+ ion channels in stimulating vasodilatation by altering the membrane potential of vascular smooth muscle cells. We present evidence that the K+ channels are modulated by a direct action of non-steroidal antiinflammatory drugs (NSAIDs) to activate the K+ ion channels

Improving regional ozone modeling through systematic evaluation of errors using the aircraft observations during the International Consortium for Atmospheric Research on Transport and Transformation

During the operational phase of the ICARTT field experiment in 2004, the regional air quality model STEM showed a strong positive surface bias and a negative upper troposphere bias (compared to observed DC-8 and WP-3 observations) with respect to ozone. After updating emissions from NEI 1999 to NEI 2001 (with a 2004 large point sources inventory update), and modifying boundary conditions, low-level model bias decreases from 11.21 to 1.45 ppbv for the NASA DC-8 observations and from 8.26 to −0.34 for the NOAA WP-3. Improvements in boundary conditions provided by global models decrease the upper troposphere negative ozone bias, while accounting for biomass burning emissions improved model performance for CO. The covariances of ozone bias were highly correlated to NOz, NOy, and HNO3 biases. Interpolation of bias information through kriging showed that decreasing emissions in SE United States would reduce regional ozone model bias and improve model correlation coefficients. The spatial distribution of forecast errors was analyzed using kriging, which identified distinct features, which when compared to errors in postanalysis simulations, helped document improvements. Changes in dry deposition to crops were shown to reduce substantially high bias in the forecasts in the Midwest, while updated emissions were shown to account for decreases in bias in the eastern United States. Observed and modeled ozone production efficiencies for the DC-8 were calculated and shown to be very similar (7.8) suggesting that recurring ozone bias is due to overestimation of NOx emissions. Sensitivity studies showed that ozone formation in the United States is most sensitive to NOx emissions, followed by VOCs and CO. PAN as a reservoir of NOx can contribute to a significant amount of surface ozone through thermal decomposition

Assessing a New Clue to How Much Carbon Plants Take Up

Current climate models disagree on how much carbon dioxide land ecosystems take up for photosynthesis. Tracking the stronger carbonyl sulfide signal could help