The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy.

Dominant mutations in ubiquitously expressed transfer RNA (tRNA) synthetase genes cause axonal peripheral neuropathy, accounting for at least six forms of Charcot-Marie-Tooth (CMT) disease. Genetic evidence in mouse and Drosophila models suggests a gain-of-function mechanism. In this study, we used in vivo, cell type­specific transcriptional and translational profiling to show that mutant tRNA synthetases activate the integrated stress response (ISR) through the sensor kinase GCN2 (general control nonderepressible 2). The chronic activation of the ISR contributed to the pathophysiology, and genetic deletion or pharmacological inhibition of Gcn2 alleviated the peripheral neuropathy. The activation of GCN2 suggests that the aberrant activity of the mutant tRNA synthetases is still related to translation and that inhibiting GCN2 or the ISR may represent a therapeutic strategy in CMT.

The G-spot: a modern gynecologic myth.

The G-spot is an allegedly highly erogenous area on the anterior wall of the human vagina. Since the concept first appeared in a popular book on human sexuality in 1982, the existence of the spot has become widely accepted, especially by the general public. This article reviews the behavioral, biochemical, and anatomic evidence for the reality of the G-spot, which includes claims about the nature of female ejaculation. The evidence is far too weak to support the reality of the G-spot. Specifically, anecdotal observations and case studies made on the basis of a tiny number of subjects are not supported by subsequent anatomic and biochemical studies.

Baroreceptor afferent discharge in the pregnant rat.

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases ¿phenylephrine (PE), 1.5-24 microg. kg(-1). min(-1) and 1-16 microg/kg and decreases ¿sodium nitroprusside (SNP), 5-80 microg. kg(-1). min(-1) and 0.05-16 microg/kg in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions (P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.

Male entertainment award winners are older than female winners.

It has been said that in the entertainment industry after a certain age women have a harder time being as successful as men. Four analyses of the ages of male and female Oscar winners, Oscar nominees, Emmy winners, and Grammy winners over the past 25 years showed that in all four groups women were, on the average, younger than the men. Two interpretations of these differences are delineated.

Pregnancy alters cardiac receptor afferent discharge in rats.

Reflex effects of cardiac receptor (CR) stimulation are attenuated in pregnant rats. We tested whether CR afferent discharge is reduced during pregnancy by measuring single fiber activity in response to increases in right atrial pressure (RAP) in anesthetized pregnant and virgin rats with sinoaortic denervation. Single fiber activity was isolated from fine filaments of the right cervical vagus nerve. Changes in CR discharge, RAP, and arterial pressure were recorded in response to atrial saline injections (25-300 microl). Resting RAP was similar between groups, and spontaneous CR discharge was similar in pregnant rats (1.95+/-0.21 Hz) and in low-frequency (LF) receptors in virgin rats (1.30+/-0.2 Hz). In virgin, but not pregnant rats, a subset (24%) of CR had higher-frequency (HF) spontaneous discharge (9.91+/-1.19 Hz). During stimulation, the level of RAP above which CR firing increased was significantly higher in pregnant rats, but CR activity was clustered into an LF discharge range. Thus gestation appears to reduce the activity of CR afferents, possibly by increasing stimulus threshold or by selective inactivation of a subset of HF discharging receptors.

Effect of cardiac receptor stimulation on renal vascular resistance in the pregnant rat.

Stimulation of cardiac receptors (CR) evokes blunted reflex reductions in mean arterial pressure (MAP) in pregnant compared with virgin rats. Because CR-mediated sympathoinhibition has preferential effects on the kidney, we tested whether, during pregnancy, renal vascular resistance (RVR) changes less in response to CR stimulation and investigated possible mechanisms. MAP, right atrial pressure, renal sympathetic nerve activity (RSNA), renal blood flow (RBF), and RVR were measured in anesthetized animals in response to CR stimulation by graded atrial injections of saline. Baseline MAP and RVR and reflex changes in these variables during CR stimulation were reduced in late-pregnant vs. virgin rats (P<0.05). Reflex changes in RSNA were attenuated in pregnant rats, but changes in RBF as a function of RSNA were similar in both groups. ANG II AT(1)-receptor blockade increased basal RBF more in virgin rats (P<0.05), but between-group differences in reflex changes in MAP, RSNA, and RVR were maintained after AT(1) blockade. Thus during CR simulation, reflex changes in RVR were reduced in pregnant versus virgin rats. This difference does not appear to involve differential effects of ANG II.

A demonstration of auditory top-down processing.

A simple demonstration of auditory top-down processing is described in which one speech embedded in several others becomes much clearer when participants read a text of the target speech at the same time as they hear it.

Correlations for weight, height and two measures of batting performance.

The hypothesis that heavier baseball players are better batters was examined in two correlational studies of major league baseball players' performance. Neither height nor weight was significantly correlated with batting average. Both variables correlated significantly and positively with the number of home runs hit by American League players in the 1997 season. After partial correlations were computed, only the correlation between weight and number of home runs hit remained significant.

Comprehensive review of biorhythm theory.

Biorhythm theory which became popular with the general public in the late 1960s held that three different biorhythm cycles influenced three different general aspects of human behavior. There was a 23-day cycle which influenced physical aspects of behavior. A 28-day cycle influenced emotions and a 33-day cycle influenced intellectual functions. Further, according to the theory, these three cycles started at birth and progressed, sinusoidally, throughout life varying not a bit with environmental or physiological factors. This paper reviews 134 studies of biorhythm theory, both published and unpublished. 35 of those reported some support for biorhythm theory. Careful examination of these studies identified methodological and statistical errors that account for the claimed findings supporting the theory. Another 99 studies, covering many different variables, yielded no support. The conclusion is that biorhythm theory is not valid.

Nitric oxide mediation of cardiac receptor reflex responses in the pregnant rat.

OBJECTIVES: Our purpose was to determine the contribution of centrally released nitric oxide to baseline sympathetic tone and reflex cardiovascular responses to cardiac stretch in the pregnant rat. STUDY DESIGN: Baseline blood pressure and renal sympathetic nerve activity and reflex changes in these variables in response to intraatrial saline solution injections were measured in anesthetized pregnant (n = 24) and virgin (n = 27) rats before and after bilateral microinjection of L-nitroarginine methyl ester (0.01 to 1 micromol) into the dorsal medulla. Data were analyzed with use of nonparametric analysis of variance. RESULTS: L-Nitroarginine methyl ester microinjection altered basal blood pressure and sympathetic nerve activity (p < 0.05) in virgin but not pregnant rats. L-Nitroarginine methyl ester significantly and equivalently attenuated the reflex sympathoinhibitory and depressor responses to cardiac stretch for 40 minutes in pregnant and virgin animals. CONCLUSION: Central nitric oxide does not modulate basal sympathetic tone in the pregnant rat but is released in the medulla in response to cardiac stretch and plays a role in reflex cardiovascular responses similar to that in virgin rats.

National Hockey League players from North America are more violent than those from Europe.

It is commonly believed by hockey fans that European hockey players rely more on skill while. North American players are more violent. The number of penalty minutes gathered by European and North American players in the National Hockey League's 1995-1996 season was examined. When corrected for the low proportion of European players, North American players had significantly more penalty minutes than European players.

Failure to demonstrate selective deficit in the native language following surgery to the left perisylvian area.

Gomez-Tortosa, Martin, Gaviria, Charbel, and Ausman (1995) reported a case of a Spanish-English bilingual with a left perisylvian arteriovenous malformation that was surgically resected. They claimed that, following the surgery, the patient showed a selective deficit in her native Spanish. Statistical analysis of the data in the report provides no support for this claim.

Proofreaders' decreased Stroop interference.

12 professional proofreaders and 12 control subjects performed a Stroop color-word task. The control subjects showed significantly more Stroop interference than did the proofreaders. It appears that a career in proofreading makes it easier for subjects to ignore the meaning of word stimuli.

Sex differences in the processing of odd and even numbers.

Previous research has shown that decisions about odd numbers take longer than decision about even numbers (the "odd effect"). It has also been shown that females are better at processing linguistic stimuli and males are better at processing spatial stimuli. In the present experiment, male and female subjects made odd versus even classification judgments on numbers presented visually in three different formats: digits, number words, and dot patterns. Males showed longer decision times for odd numbers only when the numbers were presented in the dot pattern format. Females showed this effect only when the stimuli were presented in the word format. These results suggest that a differential speed of response to odd and even numbers is found most strongly when the stimuli are presented in a format which is processed more efficiently by the subjects. This finding may imply that the effect is being produced by some higher order cognitive process, based on higher order representations that do not necessarily involve linguistic or verbal coding.

Gestational effects on volume-sensitive cardiopulmonary receptor reflexes in the rat.

We tested the hypothesis that augmented reflex sympathoinhibition mediated by volume-sensitive cardiopulmonary (CP) receptors contributes to the vasodilation of pregnancy by comparing responses to acute volume expansion in 21-day-pregnant and age-matched virgin rats (n = 7) that were anesthetized (pentobarbital sodium, 50 mg/kg ip), paralyzed (gallamine triethiodide, 25 mg/kg iv), ventilated, and had undergone bilateral sinoaortic denervation. CP receptors were stimulated with intra-atrial injections of saline (50, 100, 200, and 300 microliter), and the following variables were recorded: 1) mean right atrial pressure (MRAP) to index the afferent stimulus intensity; 2) cell discharge in the nucleus tractus solitarii (NTS), the primary central terminus for CP afferents; and 3) mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to assess efferent reflex effects. Basal MAP was significantly lower in pregnant (71.5 +/- 3.8 mmHg) than in virgin rats (86.6 +/- 3.1 mmHg), and plasma volume was expanded in the pregnant group (17.6 +/- 1.1 vs. 10.0 +/- 0.7 ml, P < 0.05). Baseline MRAP was similar between groups. Saline injections evoked graded increases in MRAP, which were larger in gravid animals (P < 0.05). Volume injections evoked similar changes in NTS cell discharge between groups, but the responses were nongraded. Despite larger changes in MRAP in gravid rats, reflex effects on RSNA and HR were similar to those in control animals, and effects on MAP were attenuated in the pregnant group. We conclude that larger changes in MRAP in pregnant rats during stimulation of CP receptors are not associated with larger changes in central or efferent components of this reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of autonomic blockade on pressor responses to vasopressin in pregnant rats.

OBJECTIVE: We tested the hypothesis that gestational changes in reflex neural control of the heart and vasculature contribute to altered cardiovascular responses to vasopressin during pregnancy. STUDY DESIGN: Changes in mean arterial pressure, cardiac output, total peripheral resistance, and heart rate were measured in response to constant infusion of arginine vasopressin (0.15 to 2.5 mU/kg/min) in conscious pregnant and virgin rats (n = 9) with total autonomic blockade plus restoration of baseline hemodynamics by norepinephrine infusion. RESULTS: Resting cardiac output was 40% higher and total peripheral resistance 30% lower in pregnant animals (p < 0.01). Constant infusion of arginine vasopressin evoked equivalent changes in mean arterial pressure in both groups, but the respective contributions of cardiac output and total peripheral resistance to mean arterial pressure differed between groups. Cardiac output was unchanged and the increase in total peripheral resistance was significantly blunted in pregnant vs virgin rats during arginine vasopressin infusion. Control data in nonblocked revealed similar pressor responses to arginine vasopressin in gravid compared with virgin rats but no differences in the contributions of cardiac output and total peripheral resistance to the change in mean arterial pressure. CONCLUSION: These findings suggest that neural modulation of arginine vasopressin-induced hypertension is altered during pregnancy and are consistent with a reduction in intrinsic vascular sensitivity to arginine vasopressin during gestation.