TNF-α/TNFR1 Signaling Is Required for the Development and Function of Primary Nociceptors

SummaryPrimary nociceptors relay painful touch information from the periphery to the spinal cord. Although it is established that signals generated by receptor tyrosine kinases TrkA and Ret coordinate the development of distinct nociceptive circuits, mechanisms modulating TrkA or Ret pathways in developing nociceptors are unknown. We have identified tumor necrosis factor (TNF) receptor 1 (TNFR1) as a critical modifier of TrkA and Ret signaling in peptidergic and nonpeptidergic nociceptors. Specifically, TrkA+ peptidergic nociceptors require TNF-α-TNFR1 forward signaling to suppress nerve growth factor (NGF)-mediated neurite growth, survival, excitability, and differentiation. Conversely, TNFR1-TNF-α reverse signaling augments the neurite growth and excitability of Ret+ nonpeptidergic nociceptors. The developmental and functional nociceptive defects associated with loss of TNFR1 signaling manifest behaviorally as lower pain thresholds caused by increased sensitivity to NGF. Thus, TNFR1 exerts a dual role in nociceptor information processing by suppressing TrkA and enhancing Ret signaling in peptidergic and nonpeptidergic nociceptors, respectively

Kinematic determinants of scoring success in the fencing flick: Logistic and linear multiple regression analysis.

Sport fencing is an open-skilled combat sport practiced around the world. Although previous research addressed kinematics of the lunge and fleche, there are currently no studies on the flick. The flick is a high-level action that involves bending the blade toward the opponent, much like a whip or fly-fishing cast. The aim of our research was to identify the kinematic variables that significantly influence scoring success in two elite foil fencers. In particular, we asked what aspect of the movement each individual fencer can change to improve their likelihood of scoring. Two elite foil fencers of similar skill were instructed to execute flicks at a dummy target that mimicked the opponent's shoulder. High speed video (650 fps) captured the motion of the tip of the foil, blade of the foil, and limb joints; the latter were used to calculate joint angular velocities, hand height and distance throughout the flick. Scoring success was determined with a conventional scoring box. Our results showed that the two fencers exhibited significantly different kinematics, coordination and scoring. Using three complementary regression approaches, we showed that each fencer could improve scoring by changing specific aspects of their kinematics. For fencer A, only improvement in consistency in distance from the target would improve scoring. For fencer B, the changes were more complex. In addition to improvement in consistency in distance, fencer B could also increase (finger, wrist) or decrease (shoulder) joint angular velocity or improve consistency of limb joint angular velocities. Unexpectedly, and in contrast to common coaching practice, hand height had only a weak effect, possibly because both fencers had learnt to keep their hand high at the end of the action. In summary, our results emphasize that coaching of elite fencers should be individualized

Endogenous and exogenous factors controlling temporal abundance patterns of tropical mosquitos

The growing demand for efficient and effective mosquito control requires a better understanding of vector population dynamics and how these are modified by endogenous and exogenous factors. A long-term (11-year) monitoring data set describing the relative abundance of the saltmarsh mosquito (Aedes vigilax) in the greater Darwin region, northern Australia, was examined in a suite of Gompertz-logistic (GL) models with and without hypothesized environmental correlates (high tide frequency, rainfall, and relative humidity). High tide frequency and humidity were hypothesized to influence saltmarsh mosquito abundance positively, and rainfall was hypothesized to correlate negatively by reducing the availability of suitable habitats (moist substrata) required by ovipositing adult female mosquitoes. We also examined whether environmental correlates explained the variance in seasonal carrying capacity (K) because environmental stochasticity is hypothesized to modify population growth rate (r), carrying capacity, or both. Current and lagged-time effects were tested by comparing alternative population dynamics models using three different information criteria (Akaike's Information Criterion [corrected; AICc], Bayesian Information Criterion [BIC], and cross-validation [C-V]). The GL model with a two-month lag without environmental effects explained 31% of the deviance in population growth rate. This increased to >70% under various model combinations of high tide frequency, rainfall, and relative humidity, of which, high tide frequency and rainfall had the highest contributions. Temporal variation in K was explained weakly by high tide frequency, and there was some evidence that the filling of depressions to reduce standing water availability has reduced Aedes vigilax carrying capacity over the study period. This study underscores the need to consider simultaneously both types of drivers (endogenous and exogenous) when predicting mosquito abundance and population growth patterns. This work also indicates that climate change, via continued increases in rainfall and higher expected frequencies and intensities of high tide events with sea level rise, will alter mosquito abundance trends in northern Australia.Guo-Jing Yang, Barry W. Brook, Peter I. Whelan, Sam Cleland and Corey J. A. Bradsha

The chemical biology of hydropersulfides (RSSH): Chemical stability, reactivity and redox roles

Recent reports indicate the ubiquitous prevalence of hydropersulfides (RSSH) in mammalian systems. The biological utility of these and related species is currently a matter of significant speculation. The function, lifetime and fate of hydropersulfides will be assuredly based on their chemical properties and reactivity. Thus, to serve as the basis for further mechanistic studies regarding hydropersulfide biology, some of the basic chemical properties/reactivity of hydropersulfides were studied. The nucleophilicity, electrophilicity and redox properties of hydropersulfides were examined under biological conditions. These studies indicate that hydropersulfides can be nucleophilic or electrophilic, depending on the pH (i.e. the protonation state) and can act as good one- and two-electron reductants. These diverse chemical properties in a single species make hydropersulfides chemically distinct from other, well-known sulfur containing biological species, giving them unique and potentially important biological function