The effect of tetrodotoxin on the sodium gating current in the squid giant axon.

The effect of tetrodotoxin (TTX) on the sodium gating current in the squid giant axon was examined by recording the current that flowed at the pulse potential at which the ionic current fell to zero, first in the absence and then in the presence of TTX. The addition of 1 microM TTX to the bathing solution had no consistent effect on the size of the initial peak of the gating current, but resulted in small changes in the timecourse of its subsequent relaxation which were mainly caused by a reduction of about one quarter in the component that has a delayed onset and may possibly arise from changes in the state of ionization of groups in the channel wall when the lumen fills with water. Our findings suggest that the binding of TTX at the outer face of the sodium channel does not interfere with the mechanisms of activation and inactivation by the voltage sensors, but has an allosteric effect on the access of internal cations to the inside of the channel.     

Fractionation of the asymmetry current in the squid giant axon into inactivating and non-inactivating components

The operation of the voltage-sensitive sodium gating system in the nerve membrane involves conformational changes that are accompanied by small asymmetrical displacement currents. The asymmetry current may be divided into a component that is inactivated by positive voltage-clamp pulses, and recovers from inactivation with exactly the same time course as the sodium conductance, and one that is not inactivated. A method is described for recording the two components separately with the aid of an inactivating prepulse. They appear to have a marked difference in their rising phases, that of the non-inactivating component being just about as fast as the imposed step in membrane potential, while the inactivating component requires some tens of microseconds to reach its peak.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

Male morphological variation and the determinants of body size in two Otiteselline fig wasps

The chalcid wasps (Hymenoptera) that develop in fig tree inflorescences(Ficus: Moraceae) have often been used to study alternativereproductive behaviors. However, recent work suggests that suchbehaviors are more complex than previously thought. We investigatedthis in Otitesella longicauda and O. rotunda. In addition toknown dimorphisms in the two species (each have "religiosa"males that use their mandibles to fight for mates in the fig,and "digitata" males that disperse from the fig to mate), wefound that religiosa males below species-specific body sizeswitch points have relatively larger mandibles and are lesssclerotized than those above. Thus, they are actually trimorphic.We suggest that the religiosa morph variation is linked to fighter/nonfighteralternative mating behaviors, with small (nonfighting) maleshaving relatively larger mandibles because they also use themto pull females out of their galls before mating. Also, we investigatedthe determinants of wasp body size, and whether females (foundresses)adjust their offspring allocation strategies according to expectedoffspring size. We found that wasp size is larger in ovariesnear the center of the fig, and more females and fewer religiosamales are laid in such ovaries than in those further away. Thisprobably indicates that foundresses lay females when they areexpected to be large because their fitness is more body size–dependentthan that of religiosa males. We then discuss the implicationsof our findings for the study of alternative reproductive behaviorsand foundress offspring allocation strategies.     

Mutation D384N Alters Recovery of the Immobilized Gating Charge in Rat Brain IIA Sodium Channels

Rat brain (rBIIA) sodium channel fast inactivation kinetics and the time course of recovery of the immobilized gating charge were compared for wild type (WT) and the pore mutant D384N heterologously expressed in Xenopus oocytes with or without the accessory beta1-subunit. In the absence of the beta1-subunit, WT and D384N showed characteristic bimodal inactivation kinetics, but with the fast gating mode significantly more pronounced in D384N. Both, for WT and D384N, coexpression of the beta1-subunit further shifted the time course of inactivation to the fast gating mode. However, the recovery of the immobilized gating charge (Qg) of D384N was clearly faster than in WT, irrespective of the presence of the beta1-subunit. This was also reflected by the kinetics of the slow Ig OFF tail. On the other hand, the voltage dependence of the Qg-recovery was not changed by the mutation. These data suggest a direct interaction between the selectivity filter and the immobilized voltage sensor S4D4 of rBIIA sodium channels.     

Dispersal and fighting in male pollinating fig wasps

For more than two decades, it has been the dogma that the males of pollinating fig wasps do not fight and that they only mate in their native fig. Their extreme degree of local mating leads to highly female biased sex ratios that should eliminate the benefits of fighting and dispersal by males. Furthermore, males sharing a fig are often brothers, and fighting may be barred by kin selection. Therefore, theory supported the presumed absence of fighting and dispersal in pollinating fig wasp males. However, we report here that in pollinating fig wasps, fighting between brothers evolved at least four and possibly six time, and dispersal by males at least twice. This finding supports the idea that competition between relatives can cancel the ameliorating effects of relatedness. The explanation to this evolutionary puzzle, as well as the consequences of male dispersal and fighting, opens the doors to exciting new research.     

Towards a framework for the evolutionary genomics of Kinetoplastids: what kind of data and how much?

The current status of kinetoplastids phylogeny and evolution is discussed in view of the recent progresses on genomics. Some ideas on a potential framework for the evolutionary genomics of kinetoplastids are presented.