bluuebunny/crossref_metadata_2025 huggingface dataset:
Verbal Self‐regulation over Time in Preschool Children at Risk for Attention and Behavior Problems
Authors: Winsler Adam , Diaz Rafael M. , Atencio David J. , McCarthy Elizabeth M. , Chabay Lori Adams
Published: August 2003

This study is a prospective, longitudinal attempt to explore behavioral self‐regulation, private speech, and speech‐action coordination in a sample of behaviorally at‐risk preschool children. Preschoolers (N= 72) were classified at age 3 years into a behaviorally at‐risk group or a comparison group on the basis of preschool teacher behavioral ratings. Children were videotaped on four different occasions across the span of almost 2 years as they completed problem‐solving tasks, and private speech, task performance, executive functioning, and speech‐action coordination were analyzed. Children identified 2 years earlier as being hard to manage were at risk for continued behavior problems at elementary school entry. Behaviorally at‐risk children consistently used more spontaneous private speech than comparison children across all observations. Both groups of children demonstrated a pattern of increasing silence with task success over time. No group differences were observed in children's speech‐action coordination at age 5 years. Intraindividual developmental changes in private speech for both groups were associated with task performance, speech‐action coordination, and executive functioning at age 5, but not with teacher‐ and parent‐reported problem behavior.
Heritability and Prevalence of Specific Fears and Phobias in Childhood
Authors: Lichtenstein Paul , Annas Peter
Published: August 2003

Fears and phobias are relatively common in childhood. Both environmental and genetic theories have tried to explain the etiology behind these conditions. However, data supporting the different theories are sparse. To investigate the relative importance of genetic and environmental influences on specific phobias and fears, parental reports of animal, situational, and mutilation fears and phobias were completed for 1106 pairs of 8‐ to 9‐year‐old Swedish twins. The prevalence of specific phobias was 7.3% for boys and 10.0% for girls. Genetic, shared environmental, and nonshared environmental effects contributed to individual differences in fears and phobias in young children, but the magnitude of the effects differed between sexes. Shared environmental effects contributed to a general susceptibility for fearfulness. Genetic and nonshared environmental effects, on the other hand, contributed both to the general susceptibility and specific fearfulness, even though these effects primarily were fear specific. These results indicate that both heritable factors as well as environmental factors such as trauma, vicarious learning, and/or negative information are important for differences in fearfulness and phobias—at least in children.
Adverse Selection and the Decline in Private Health Insurance Coverage in Australia: 1989–95
Authors: Barrett Garry F. , Conlon Robert
Published: September 2003

The decline in private health insurance coverage over the period 1989–95 is analysed using the ABS National Health Surveys. Individuals’ health status and health risk behaviours are found to be significant determinants of their decision to purchase private health insurance. At a point in time, the pool of the insured is very heterogeneous, with a mix of both good and bad health risks. It is found that the decline in insurance coverage over the period 1989–95 coincided with an increase in the degree of ‘adverse selection’ within the insured population.
Income and Health Concentration in Australia
Authors: Chotikapanich Duangkamon , Creedy John , Hopkins Sandra
Published: September 2003

This paper measures the concentration of ill‐health among income groups in Australia using health survey data from 1989–90 (Australian Bureau of Statistics 1991) and 1995 (Australian Bureau of Statistics 1997), which contain responses on self‐assessed health status and gross personal income. The technique of direct standardisation is used to control for the influence on health status of gender and age. Comparisons of the concentration of ill‐health over time and between males and females and persons living in rural and urban areas are reported. For both surveys and all groups, we find that ill‐health is concentrated among lower income groups. Concentration measures of ill‐health are higher (in absolute terms) for men than for women. In all categories apart from women, the concentration measures fell between 1989–90 and 1995 surveys.
Is Under‐Employment due to Labour Hoarding? Evidence from the Australian Workplace Industrial Relations Survey
Authors: Doiron Denise J.
Published: September 2003

In this paper, Australian data are used to study the characteristics of workers who are constrained in their hours of work. Matched employer–employee data allow us to control for their employers’ characteristics as well. In particular, the information on the firms’ state of demand provides useful evidence on the underlying cause of under‐employment. The labour hoarding model cannot explain the observed patterns involving under‐employment. Alternative explanations are offered.
Time to Ditch the Natural Rate?
Authors: Hagger A. J. , Groenewold Nicolaas
Published: September 2003

We urge macroeconomists to abandon the ‘natural rate’ as an analytical device on the ground that it has become a source of great and growing confusion. But we press them to recognise that it has great potential as a policy tool provided we grasp the central idea of a hypothetical unemployment rate, which can be compared with the actual unemployment rate. We integrate three hypothetical unemployment rates with the help of an exploratory macro model and then present a quarterly series for each for Australia for the period 1986(2) to 1997(2). We explain how such series could help in policy‐making.
Labour Market Flexibility and Immigrant Adjustment
Authors: W. Miller Paul , Neo Leanne M.
Published: September 2003

A comparative analysis of adult male immigrant earnings and unemployment in the US and Australia using a measure of expected earnings shows that immigrants in the US perform relatively well, and the pattern of the differences between immigrant adjustment in the US and Australia appears to have links to differences in methods of pay determination. The results suggest an advantage to a more flexible labour market. A simulation exercise demonstrates the sensitivity of the findings to cohort effects.
Wine Quality and Varietal, Regional and Winery Reputations: Hedonic Prices for Australia and New Zealand
Authors: Schamel Günter , Anderson Kym
Published: September 2003

We estimate hedonic price functions for premium wine from Australia and New Zealand, differentiating implicit prices for sensory quality ratings, wine varieties and regional as well as winery brand reputations over the vintages 1992–2000. The results show regional reputations have become increasingly differentiated through time (although less so for New Zealand). In particular, cool‐climate regions are becoming increasingly preferred over other regions in Australia. In each country, price premia associated with both James Halliday's and Winestate magazine's sensory quality ratings, and with Halliday's winery ratings and classic wine designations, are highly significant.
The Implications of Uncertainty for Monetary Policy
Authors: Shuetrim Geoffrey , Thompson Christopher
Published: September 2003

This paper uses a simple model of the Australian economy to empirically examine the consequences of parameter uncertainty for optimal monetary policy. Optimal policy responses are derived for a monetary authority that targets inflation and output stability. Parameter uncertainty is characterised by the estimated distribution of the model coefficient estimates. Learning is ruled out, so the monetary authority can commit to its ex ante policy response. For certain shocks, taking account of parameter uncertainty can recommend more, rather than less, activist use of the policy instrument. While this finding is specific to the model specification, parameter estimates and the shocks analysed, it contrasts with the widely held belief that the generic implication of parameter uncertainty is more conservative policy.
Corporate Board Composition, Protocols, and Voting Behavior: Experimental Evidence
Authors: Gillette Ann B. , Noe Thomas H. , Rebello Michael J.
Published: September 2003

We examine voting by a board designed to mitigate conflicts of interest between privately informed insiders and owners. Our model demonstrates that, as argued by researchers and the business press, boards with a majority of trustworthy but uninformed “watchdogs” can implement institutionally preferred policies. Our laboratory experiments strongly support this conclusion. Our model also highlights the necessity of penalties on insiders when there is dissension among board members. However, penalties for dissent appeared to have little impact on the experimental outcomes.
Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor
Authors: Bonnington Jennifer K. , McNaughton Peter A.
Published: August 2003

Nerve growth factor (NGF) causes a rapid sensitisation of nociceptive sensory neurones to painful thermal stimuli owing to an action on the heat and capsaicin receptor TRPV1 (formerly known as VR1). We have developed a new technique to study this rapid sensitisation of TRPV1 by monitoring the effects of NGF on the increase in intracellular calcium concentration ([Ca2+]i) following exposure to capsaicin. Brief applications of capsaicin caused a rise in [Ca2+]i, and NGF was found to enhance this rise in 37 % of capsaicin‐responsive neurones within 2 min. Pathways responsible for transducing the sensitisation of TRPV1 by TrkA, the NGF receptor, were characterised by observing the effects of inhibitors of key members of NGF‐activated second messenger signalling cascades. Specific inhibitors of the ras/MEK (mitogen‐activated protein and extracellular signal‐regulated kinases) pathway and of phospholipase C did not abolish the NGF‐induced sensitisation, but wortmannin, a specific inhibitor of phosphatidylinositol‐3‐kinase (PI3K), totally abolished the effect of NGF. Pharmacological blockade of protein kinase C (PKC) or calcium‐calmodulin‐dependent protein kinase II (CaMK II) activation also prevented NGF‐induced sensitisation, while blockade of protein kinase A (PKA) was without effect. These data indicate that the crucial early pathway activated by NGF involves PI3K, while PKC and CaMK II are also involved, probably at subsequent stages of the NGF‐activated signalling pathway.
Attenuation of metabolic heat production and cold‐escape/warm‐seeking behaviour during a cold exposure following systemic salt loading in rats
Authors: Konishi Masahiro , Nagashima Kei , Asano Kento , Kanosue Kazuyuki
Published: August 2003

The reduction of body core temperature (Tcore) after salt loading has been reported. In this study, we tested the hypothesis that, during a cold exposure in rats, (1) salt loading would decrease metabolic rate (MR), reducing Tcore, but (2) Tcore would be maintained when cold‐escape/warm‐seeking behaviour is available. In the first experiment (n= 7), MR and Tcore were measured by indirect calorimetry and telemetry, respectively, during 26, 20 and 10 °C exposure for 1 h each, in that order. In the second experiment (n= 7), each rat was placed in an operant system during the same exposure protocol as in the first experiment, where it could trigger a 40 °C air reward for 30 s at 20 and 10 °C by moving into specific areas (operant behaviour). In each experiment, rats repeated the same protocol twice with a subcutaneous injection (10 ml kg−1) of either isotonic saline (154 mm) or hypertonic saline (2500 mm). In the first experiment, MR in the isotonic‐saline trial increased (P < 0.05) at 20 and 10 °C compared with that at 26 °C by 21 ± 5 and 48 ± 6 %, respectively (means ±s.e.m.), with Tcore unchanged. However, values for MR and Tcore in the hypertonic‐saline trial were lower (P < 0.05) than those in the isotonic‐saline trial in any ambient temperature. In the second experiment, Tcore was also lower (P < 0.05) in the hypertonic‐saline trial than in the isotonic‐saline trial. The counts of the operant behaviour in the hypertonic‐saline trial remained unchanged in each exposure period, but those in the isotonic‐saline trial increased (P < 0.05) at 10 °C. These results may suggest that salt loading attenuates both metabolic and behavioural thermoregulatory responses to the cold.
Ca2+‐independent, but voltage‐ and activity‐dependent regulation of the NMDA receptor outward K+ current in mouse cortical neurons
Authors: Ichinose Tomomi , Yu Shun , Wang Xue Qing , Yu Shan Ping
Published: August 2003

To test the novel hypothesis that the K+ efflux mediated by NMDA receptors might be regulated differently than the influx of Ca2+ and Na+ through the same receptor channels, NMDA receptor whole‐cell currents carried concurrently or individually by Ca2+, Na+ and K+ were analysed in cultured mouse cortical neurons. In contrast to the NMDA inward current carried by Ca2+ and Na+, the NMDA receptor outward K+ current or NMDA‐K current, recorded either in the presence or absence of extracellular Ca2+ and Na+, and at different or the same membrane potentials, showed much less sensitivity to alterations in intracellular Ca2+ concentration and underwent little rundown. In line with a selective regulation of the NMDA receptor K+ permeability, the ratio of the NMDA inward/outward currents decreased, and the reversal potential of composite NMDA currents recorded in physiological solutions shifted by −8.5 mV after repeated activation of NMDA receptors. Moreover, a depolarizing pre‐pulse of a few seconds or a burst of brief depolarizing pulses selectively augmented the subsequent NMDA‐K current, but not the NMDA inward current. On the other hand, a hyperpolarizing pre‐pulse showed the opposite effect of reducing the NMDA‐K current. The voltage‐ and activity‐dependent regulation of the NMDA‐K current did not require the existence of extracellular Ca2+ or Ca2+ influx; it was, however, affected by the duration of the pre‐pulse and was subject to a time‐dependent decay. The burst of excitatory activity revealed a lasting upregulation of the NMDA‐K current even 5 s after termination of the pre‐pulses. Our data reveal a selective regulation of the NMDA receptor K+ permeability and represent a novel model of voltage‐ and excitatory activity‐dependent plasticity at the receptor level.
GABAA and glycine receptors in regulation of intercostal and abdominal expiratory activity in vitro in neonatal rat
Authors: Iizuka3 Makito
Published: August 2003

The roles played by GABAA and glycine receptors in inspiratory‐expiratory motor co‐ordination and in tonic inhibitory regulation of expiratory motor activity were studied using brainstem‐spinal cord (‐rib) preparations from neonatal rats. Inspiratory activity was recorded from the C4 ventral root. Expiratory activity in internal intercostal muscle, internal oblique muscle or T13 ventral root was evoked by a decrease in perfusate pH from 7.4 to 7.1 (i.e. from normal to low pH conditions) and was limited to the first part of the expiratory phase. Under low pH conditions, bath application of 10 μm bicuculline, a GABAA receptor antagonist, caused the inspiratory burst to overlap the expiratory burst in 2/7 preparations. Overlapping of the expiratory burst with the inspiratory burst was observed in 7/7 preparations made under 10 μm bicuculline. Furthermore, such preparations exhibited expiratory bursts under bicuculline‐containing normal pH conditions. Local application of 10 μm bicuculline to the brainstem under normal pH conditions evoked expiratory bursts, some of which overlapped the inspiratory bursts. Picrotoxin, another antagonist of the GABAA receptor, had similar effects. Under normal pH conditions, application of strychnine (0.2‐ 2.0 μm; a glycine receptor antagonist) to the brainstem did not evoke expiratory bursts. On subsequent application of strychnine‐containing low pH solution, expiratory bursts were evoked and some (0.5 μm) or all (2.0 μm) of these overlapped the inspiratory burst. Simultaneous application of picrotoxin and strychnine to the brainstem evoked expiratory bursts that overlapped the inspiratory bursts and a subsequent decrease in perfusate pH to 7.1 increased the frequency of the respiratory rhythm. It was a characteristic finding that the duration of the expiratory burst exceeded that of the inspiratory burst under control low pH conditions. This remained true during concurrent blockade of GABAA and glycine receptors. The results suggest that in the in vitro preparation from neonatal rats: (1) GABAA and glycine receptors within the brainstem play important roles in the co‐ordination between inspiratory and expiratory motor activity, (2) tonic inhibition via GABAA receptors, but not glycine receptors, plays a role in the regulation of expiratory motor activity and (3) inspiratory and expiratory burst termination is independent of both GABAA and glycine receptors.
Distribution and regulation of expression of serum‐ and glucocorticoid‐induced kinase‐1 in the rat kidney
Authors: de la Rosa Diego Alvarez , Coric Tatjana , Todorovic Natasa , Shao Deren , Wang Tong , Canessa Cecilia M.
Published: August 2003

The serum‐ and glucocorticoid‐induced kinase‐1 (sgk1) increases the activity of a number of epithelial ion channels and transporters. The present study examines the distribution and subcellular localization of sgk1 protein in the rat kidney and the regulation of levels of expression induced by steroids. The results indicate that the kidney expresses predominantly the sgk1 isoform with a distribution restricted to the thick ascending limb of Henle, distal convoluted, connecting and cortical collecting tubules. Within cells, sgk1 strongly associates with the microsomal fraction of homogenates and it colocalizes with the Na+,K+‐ATPase to the basolateral membrane. Analysis of the levels of expression of sgk1 by Western blotting and immunohistochemistry indicates constitutive high expression under basal conditions. Approximately half of the basal level is maintained by glucocorticoids whereas physiological fluctuations of aldosterone produce minor changes in sgk1 abundance in adrenal‐intact animals. These results do not support the notion that physiological changes of aldosterone concentration turn the expression of sgk1 ‘on and off’ in the mammalian kidney. Additionally, localization of sgk1 to the basolateral membrane indicates that the effects mediated by sgk1 do not require a direct interaction with the ion channels and transporters whose activity is modulated, since most of these proteins are located in the apical membrane of renal epithelial cells.
Selectivity of macaque ventral intraparietal area (area VIP) for smooth pursuit eye movements
Authors: Schlack Anja , Hoffmann Klaus‐Peter , Bremmer Frank
Published: August 2003

In the posterior parietal cortex (PPC) of the macaque, spatial and motion signals arising from different sensory signals converge. One of the functional subregions within the PPC, the ventral intraparietal area (VIP), is thought to play an important role for the multisensory encoding of self‐ and object motion. In the present study we analysed the activity of area VIP neurons related to smooth pursuit eye movements (SPEMs). Fifty‐three per cent of the neurons (123/234) were selective for the direction of the SPEMs. As evident from control experiments, activity observed during smooth eye movements was more closely related to extraretinal signals than visual parameters. In addition, we examined the sensitivity of area VIP neurons for the velocity of SPEMs. Seventy‐four per cent of the pursuit‐related neurons had a significant velocity tuning. There was a clear preference for high velocities. Eighty‐six per cent of the neurons preferred the highest pursuit velocity (40 deg s−1) employed in our study. In everyday life, high pursuit velocities most frequently occur if the pursuit target is located in near‐extrapersonal space, i.e. the action space of the head. Together with previous findings, the current results thus suggest that the information provided by VIP neurons may be used to encode motion in near‐extrapersonal space and to guide and co‐ordinate smooth eye and head movements within this very part of space.
Differential effect of muscle vibration on intracortical inhibitory circuits in humans
Authors: Rosenkranz Karin , Rothwell John C.
Published: August 2003

Low amplitude muscle vibration (0.5 ms; 80 Hz; duration 1.5 s) was applied in turn to each of three different intrinsic hand muscles (first dorsal interosseus, FDI; abductor pollicis brevis, APB; and abductor digiti minimi, ADM) in order to test its effect on the EMG responses evoked by transcranial magnetic stimulation (TMS). Recordings were also taken from flexor and extensor carpi radialis (FCR and ECR, respectively). We evaluated the amplitude of motor evoked potentials (MEPs) produced by a single TMS pulse, short interval intracortical inhibition and facilitation (SICI and ICF) and long interval intracortical inhibition (LICI). TMS pulses were applied 1 s after the start of vibration with subjects relaxed throughout. Vibration increased the amplitude of MEPs evoked in the vibrated muscle (162 ± 6 % of MEP with no vibration; mean ±s.e.m.), but suppressed MEPs in the two non‐vibrated hand muscles (72 ± 9 %). Compared with no vibration (test response reduced to 51 ± 5 % of control), there was less SICI in the vibrated muscle (test response reduced to 92 ± 28 % of control) and more in the non‐vibrated hand muscles (test response reduced to 27 ± 5 % of control). The opposite occurred for LICI: compared with the no vibration condition (test response reduced to 33 ± 6 % control), there was more LICI in the vibrated muscle (test response reduced to 17 ± 3 % control) than in the non‐vibrated hand muscles (test response reduced to 80 ± 11 % control) even when the intensity of the test stimulus was adjusted to compensate for the changes in baseline MEP. There was no effect on ICF. Cutaneous stimulation of the index finger (80 Hz, 1.5 s duration, twice sensory threshold) had no consistent differential effect on any of the parameters. We conclude that vibratory input from muscle can differentially modulate excitability in motor cortical circuits.
Human skeletal muscle sympathetic nerve activity, heart rate and limb haemodynamics with reduced blood oxygenation and exercise
Authors: Hanada Akiko , Sander Mikael , González‐Alonso José
Published: August 2003

Acute systemic hypoxia causes significant increases in human skeletal muscle sympathetic nerve activity (MSNA), heart rate and ventilation. This phenomenon is thought to be primarily mediated by excitation of peripheral chemoreceptors sensing a fall in arterial free oxygen partial pressure (Pa,O2). We directly tested the role of Pa,O2 on MSNA (peroneal microneurography), heart rate, ventilation and leg haemodynamics (n= 7‐8) at rest and during rhythmic handgrip exercise by using carbon monoxide (CO) to mimic the effect of systemic hypoxia on arterial oxyhaemoglobin (≈20 % lower O2Hba), while normalising or increasing Pa,O2 (range 40‐620 mmHg). The four experimental conditions were: (1) normoxia (Pa,O2≈110 mmHg; carboxyhaemoglobin (COHb) ≈2 %); (2) hypoxia (Pa,O2≈40 mmHg; COHb ≈2 %); (3) CO + normoxia (Pa,O2≈110 mmHg; COHb ≈23 %); and (4) CO + hyperoxia (Pa,O2≈620 mmHg; COHb ≈24 %). Acute hypoxia augmented sympathetic burst frequency, integrated MSNA, heart rate and ventilation compared to normoxia over the entire protocol (7–13 bursts min−1, 100‐118 %, 13‐17 beats min−1, 2‐4 l min−1, respectively, P < 0.05). The major new findings were: (1) CO + normoxia and CO + hyperoxia also elevated MSNA compared to normoxia (63–144 % increase in integrated MSNA; P < 0.05) but they did not increase heart rate (62–67 beats min−1) or ventilation (6.5–6.8 l min−1), and (2) despite the 4‐fold elevation in MSNA with hypoxaemia and exercise, resting leg blood flow, vascular conductance and O2 uptake remained unchanged. In conclusion, the present results suggest that increases in MSNA with CO are not mediated by activation of the chemoreflex, whereas hypoxia‐induced tachycardia and hyperventilation are mediated by activation of the chemoreflex in response to the decline in Pa,O2. Our findings also suggest that Pa,O2 is not an obligatory signal involved in the enhanced MSNA with reduced blood oxygenation.
Measurement of voluntary activation of fresh and fatigued human muscles using transcranial magnetic stimulation
Authors: Todd Gabrielle , Taylor Janet L. , Gandevia S. C.
Published: August 2003

Recently, transcranial magnetic stimulation of the motor cortex (TMS) revealed impaired voluntary activation of muscles during maximal efforts. Hence, we evaluated its use as a measure of voluntary activation over a range of contraction strengths in both fresh and fatigued muscles, and compared it with standard twitch interpolation using nerve stimulation. Subjects contracted the elbow flexors isometrically while force and EMG from biceps and triceps were recorded. In one study, eight subjects made submaximal and maximal test contractions with rests to minimise fatigue. In the second study, eight subjects made sustained maximal contractions to reduce force to 60 % of the initial value, followed by brief test contractions. Force responses were recorded following TMS or electrical stimulation of the biceps motor nerve. In other contractions, EMG responses to TMS (motor evoked potentials, MEPs) or to stimulation at the brachial plexus (maximal M waves, Mmax) were recorded. During contractions of 50 % maximum, TMS elicited large MEPs in biceps (> 90 % Mmax) which decreased in size (to ≈70 % Mmax) with maximal efforts. This suggests that faster firing rates made some motor units effectively refractory. With fatigue, MEPs were also smaller but remained > 70 % Mmax for contractions of 50–100 % maximum. For fresh and fatigued muscle, the superimposed twitch evoked by motor nerve and motor cortex stimulation decreased with increasing contraction strength. For nerve stimulation the relation was curvilinear, and for TMS it was linear for contractions of 50‐100 % maximum (r2= 1.00). Voluntary activation was derived using the expression: (1 – superimposed twitch/resting twitch) × 100. The resting twitch was measured directly for nerve stimulation and for TMS, it was estimated by extrapolation of the linear regression between the twitch and voluntary force. For cortical stimulation, this resulted in a highly linear relation between voluntary activation and force. Furthermore, the estimated activation corresponded well with contraction strength. Using TMS or nerve stimulation, voluntary activation was high during maximal efforts of fresh muscle. With fatigue, both measures revealed reduced voluntary activation (i.e. central fatigue) during maximal efforts. Measured with TMS, this central fatigue accounted for one‐quarter of the fall in maximal voluntary force. We conclude that TMS can quantify voluntary activation for fresh or fatigued muscles at forces of 50–100 % maximum. Unlike standard twitch interpolation of the elbow flexors, voluntary activation measured with TMS varies in proportion to voluntary force, it reveals when extra output is available from the motor cortex to increase force, and it elicits force from all relevant synergist muscles.
Acute and chronic effects of oestrogen on endothelial tissue‐type plasminogen activator release in postmenopausal women
Authors: Hoetzer Greta L. , Stauffer Brian L. , Irmiger Heather M. , Ng Marilyn , Smith Derek T. , DeSouza Christopher A.
Published: August 2003

The capacity of vascular endothelium to locally release tissue‐type plasminogen activator (t‐PA) represents an important endogenous defence mechanism against intravascular fibrin deposition and thrombosis. We determined the influence of chronic and acute oestrogen administration on endothelial t‐PA release in postmenopausal women. Sixty‐three healthy postmenopausal women were studied: 31 non‐users (age 58 ± 1 years) and 32 users of hormone replacement therapy, including oestrogen alone (ORT: 62 ± 2 years; n= 15) and in combination with progesterone (HRT: 57 ± 1 years; n= 17). Net endothelial t‐PA release was determined in vivo, in response to intrabrachial infusions of bradykinin and sodium nitroprusside. To examine the acute effects of oestrogen on endothelial t‐PA release, bradykinin and sodium nitroprusside dose‐response curves were repeated in the presence of 17 β‐oestradiol in 20 of the 31 non‐users. Net endothelial release of t‐PA was ≈30 % higher (P < 0.01) in women taking ORT (from 2.0 ± 1.0 to 83.6 ± 9.2 ng (100 ml tissue)−1 min−1) compared with those taking HRT (from 1.4 ± 0.4 to 63.5 ± 5.6 ng (100 ml tissue)−1 min−1) and those not taking supplementation (1.0 ± 0.7 to 63.0 ± 4.7 ng (100 ml tissue)−1 min−1). Intra‐arterial infusion of 17 β‐oestradiol significantly potentiated bradykinin‐induced t‐PA release. Net endothelial release of t‐PA was ≈45 % higher (P < 0.01) after (from 1.0 ± 0.8 to 87.4 ± 9.9 ng (100 ml tissue)−1 min−1) versus before (1.2 ± 0.6 to 60.8 ± 5.6 ng (100 ml tissue)−1 min−1) acute 17 β‐oestradiol administration. Our results suggest that oestrogen has a direct modulatory effect on the capacity of the endothelium to release t‐PA in healthy postmenopausal women. However, progesterone appears to oppose the favourable influence of oestrogen on endothelial fibrinolytic capacity.
Dynamic Receptive Fields of Reconstructed Pyramidal Cells in Layers 3 and 2 of Rat Somatosensory Barrel Cortex
Authors: Brecht Michael , Roth Arnd , Sakmann Bert
Published: September 2003

Whole‐cell voltage recordings were made in vivo from subsequently reconstructed pyramidal neurons (n= 30) in layer 3 (L3) and layer 2 (L2) of the barrel cortex of urethane‐anaesthetised rats. Average resting membrane potentials were well below (15−40 mV) action potential (AP) initiation threshold. The average spontaneous AP activity (0.068 ± 0.22 APs s−1) was low. Principal whisker (PW) deflections evoked postsynaptic potentials (PSPs) in almost all cells of a PW column but evoked AP activity (0.031 ± 0.056 APs per PW stimulus 6 deg deflection) was low indicating ‘sparse’ coding by APs. Barrel‐related cells (n= 16) have their soma located above a barrel and project their main axon through the barrel whereas septum‐related cells (n= 8) are located above and project their main axon through the septum between barrels. Both classes of cell had broad subthreshold receptive fields (RFs) which comprised a PW and several (> 8) surround whiskers (SuW). Barrel‐related cells had shorter PSP onset latencies (9.6 ± 4.6 ms) and larger amplitude PW stimulus responses (9.1 ± 4.5 mV) than septum‐related cells (23.3 ± 16.5 ms and 5.0 ± 2.8 mV, respectively). The dendritic fields of barrel‐related cells were restricted, in the horizontal plane, to the PW column width. Their axonal arbors projected horizontally into several SuW columns, preferentially those representing whiskers of the same row, suggesting that they are the major anatomical substrate for the broad subthreshold RFs. In barrel‐related cells the response time course varied with whisker position and subthreshold RFs were highly dynamic, expanding in size from narrow single‐whisker to broad multi‐whisker RFs, elongated along rows within 10‐150 ms following a deflection. The response time course in septum‐related cells was much longer and almost independent of whisker position. Their broad subthreshold RF suggests that L2/3 cells integrate PSPs from several barrel columns. We conclude that the lemniscal (barrel‐related) and paralemniscal (septum‐related) afferent inputs remain anatomically and functionally segregated in L2/3.
Effects on the right motor hand‐area excitability produced by low‐frequency rTMS over human contralateral homologous cortex
Authors: Gilio Francesca , Rizzo Vincenzo , Siebner Hartwig R. , Rothwell John C.
Published: August 2003

Repetitive transcranial magnetic stimulation (rTMS) has long lasting effects on cortical excitability at the site of stimulation, on interconnected sites at a distance and on the connections between them. In the present experiments we have used the technique of transcallosal inhibition between the motor cortices to examine all three effects in the same protocol. Ten healthy subjects received 900 rTMS stimuli at 1 Hz from a figure of eight coil over the left motor hand area. The intensity of rTMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115–120 % resting motor threshold). Before and after the rTMS we evaluated: (1) in the left hemisphere, the amplitude of motor‐evoked potentials (MEPs), and contralateral and ipsilateral cortical silent periods (CSP, ISP); (2) in the right hemisphere, MEP, CSP, ISP and short‐interval intracortical inhibition and intracortical facilitation (SICI/ICF), and (3) interhemispherical inhibition (IHI) from the left‐to‐right hemisphere using a paired‐pulse method. There were two main effects after rTMS to the left hemisphere: first, the amplitude of MEPs from the right hemisphere increased; second, there was a reduction in the IHI from the left‐to‐right hemisphere at interstimulus intervals of 7 and 10 ms but not at longer intervals (15–75 ms). Control experiments showed that these effects were not due to afferent inputs produced by the muscle twitches induced during the rTMS. The data are compatible with the notion that rTMS to the left hemisphere leads to reduced interhemispherical inhibition of the right hemisphere and a consequent increase in corticospinal excitability in that hemisphere.
Aquaporin gene expression and regulation in the ovine fetal lung
Authors: Liu H. , Hooper S. B. , Armugam A. , Dawson N. , Ferraro T. , Jeyaseelan K. , Thiel A. , Koukoulas I. , Wintour E. M.
Published: August 2003

Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air‐breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression before birth. Our aim was to describe the changes in AQP1, 3, 4 and 5 expression and protein levels in the fetal lung of a long‐gestation species (sheep) and in response to physiological factors known to alter fetal lung liquid dynamics. Both mRNA and high protein levels were detected for AQP1, 3, 4 and 5 by day 100 (term is ≈150 days in ovine fetuses). A cortisol infusion (120–131 days) significantly (P < 0.05) increased AQP1 (0.9 ± 0.2 (n= 4) vs.1.8 ± 0.3 (n= 5)) and AQP5 (8.8 ± 0.6 vs. 14.1 ± 1.2) mRNA levels in fetal lung (measured by real‐time PCR). Ten days of tracheal obstruction significantly (P < 0.05) decreased AQP5 mRNA levels (6.1 ± 0.9 (n= 5) vs. 2.7 ± 0.3 (n= 5)). Immunohistochemistry was used to show that protein levels changed in parallel with the mRNA changes. These findings suggest that AQPs could be involved in lung liquid production and reabsorption during fetal development in long‐gestation species.
Expression of Non‐Phosphorylatable Paxillin Mutants in Canine Tracheal Smooth Muscle Inhibits Tension Development
Authors: Tang Dale D. , Turner Christopher E. , Gunst Susan J.
Published: September 2003

The adapter protein paxillin has been implicated in the regulation of cytoskeletal organization and cell motility. Paxillin undergoes tyrosine phosphorylation in response to the contractile stimulation of smooth muscle, and the depletion of paxillin by antisense inhibits smooth muscle contraction. In the present study, acetylcholine (ACh)‐stimulation of tracheal smooth muscle tissues increased paxillin phosphorylation at tyr‐31 and tyr‐118 by three‐ to fourfold. The role of tyr‐31 and tyr‐118 phosphorylation of paxillin in smooth muscle was evaluated by introducing plasmids encoding wild type paxillin or paxillin mutants F31, F118 or F31/118 (phenylalanine substitution at tyrosine sites 31, 118) into tracheal smooth muscle strips by reversible permeabilization, and incubating the tissues for 2 days. The expression of recombinant proteins was confirmed by immunoblot and immunofluorescence analysis. Expression of the paxillin mutants F31, F118 or F31/118 inhibited the contractile response to ACh stimulation but did not inhibit the increase in myosin light chain phosphorylation. The expression of wild type paxillin had no significant affect on force or myosin light chain phosphorylation. ACh stimulation reduced G‐actin/F‐actin ratio in tissues expressing wild type paxillin; whereas the agonist‐induced decrease in G‐actin/F‐actin was inhibited in strips expressing paxillin mutant F31/118. The paxillin mutant F31/118 showed a marked decrease in their interaction with the SH2/SH3 adaptor protein CrkII but not with vinculin or focal adhesion kinase. We conclude that paxillin phosphorylation at tyr‐31 and tyr‐118 regulates active tension development during contractile stimulation. Paxillin phosphorylation at these two sites may be important in regulating actin filament dynamics and organization during smooth muscle contraction.
Kainate receptor (GluR5)‐mediated disinhibition of responses in rat ventrobasal thalamus allows a novel sensory processing mechanism
Authors: Binns K. E. , Turner J. P. , Salt T. E.
Published: August 2003

Kainate receptors have been studied extensively in vitro, but how they might function physiologically remains unclear. We studied kainate receptor modulation of synaptic responses in the rat ventrobasal thalamus using the novel antagonist LY382884 and the agonist ATPA (selective for GluR5‐containing kainate receptors) as tools. No evidence could be found for a direct contribution of kainate receptors to responses of thalamic relay cells to lemniscal (sensory) input in thalamic slices studied with the aid of intracellular and field potential recordings, using selective AMPA and NMDA receptor antagonists and LY382884. However, the GluR5 agonist ATPA reduced the IPSPs originating from the thalamic reticular nucleus. Extracellular single‐neurone recordings in anaesthetised rats showed that excitatory responses evoked by physiological vibrissa afferent stimulation were reduced by LY382884 applied iontophoretically at the recording site. This action of the antagonist was occluded when GABA receptors were blocked, indicating that the reduction in excitatory sensory responses by LY382884 is due to an action on GABAergic inhibition arising from the thalamic reticular nucleus. Further experiments showed that these actions depended on whether inhibition was evoked during activation of the excitatory receptive field rather than when inhibition was evoked from a surround vibrissa. We suggest that GluR5 is located presynaptically on inhibitory GABAergic terminals of thalamic reticular nucleus neurones, and that it is normally activated by glutamate spillover from synapses between excitatory afferents and relay neurones during physiological stimulation. We propose that this GluR5‐activated disinhibition has an important novel role in extracting sensory information from background noise.
Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles
Authors: Garnier A. , Fortin D. , Deloménie C. , Momken I. , Veksler V. , Ventura‐Clapier R.
Published: August 2003

Congestive heart failure (CHF) induces alterations in energy metabolism and mitochondrial function that span cardiac as well as skeletal muscles. Whether these defects originate from altered mitochondrial DNA copy number and/or mitochondrial gene transcription is not known at present, nor are the factors that control mitochondrial capacity in different muscle types completely understood. We used an experimental model of CHF induced by aortic banding in the rat and investigated mitochondrial respiration and enzyme activity of biochemical mitochondrial markers in cardiac, slow and fast skeletal muscles. We quantified mitochondrial DNA (mtDNA), expression of nuclear (COX IV) and mitochondrial (COX I) encoded cytochrome c oxidase subunits as well as nuclear factors involved in mitochondrial biogenesis and in the necessary coordinated interplay between nuclear and mitochondrial genomes in health and CHF. CHF induced a decrease in oxidative capacity and mitochondrial enzyme activities with a parallel decrease in the mRNA level of COX I and IV, but no change in mtDNA content. The expression of the peroxisome proliferator activated receptor gamma co‐activator 1α (PGC‐1α) gene was downregulated in CHF, as well as nuclear respiratory factor 2 and mitochondrial transcription factor A, which act downstream from PGC‐1α. Most interestingly, only the level of PGC‐1α expression was strongly correlated with muscle oxidative capacity in cardiac and skeletal muscles, both in healthy and CHF rats. Mitochondrial gene transcription is reduced in CHF, and PGC‐1α appears as a potential modulator of muscle oxidative capacity under these experimental conditions.
Spinal and supraspinal functions of noradrenaline in the frog embryo: consequences for motor behaviour
Authors: McLean David L. , Sillar Keith T.
Published: August 2003

The monoamine noradrenaline (NA) can initiate and/or modulate locomotion in a variety of vertebrates. Here we report that exogenous NA application can facilitate two completely different fictive behaviours in embryos of the common frog Rana temporaria, depending on whether spinal networks are connected to supraspinal centres. When the nervous system is intact, NA elicits a non‐rhythmic coiling motor response, reminiscent of a spontaneous behaviour appropriate to drive hatching movements, but has only minor effects on evoked swimming activity. After the spinal cord has been severed from the brain, spontaneous coiling is no longer observed, nor can NA elicit it, but the amine can ‘release’ swimming rhythm generation in response to electrical skin stimulation. The rhythm is similar, but relatively inflexible when compared to fictive swimming recorded from intact animals. Our pharmacological tests indicate that α1‐adrenoreceptors are involved in the permissive role of NA during spinalised rhythmic swimming and that the fictive coiling response to NA in intact animals involves descending inputs and the activation of β1‐adrenoreceptors. Furthermore, the subtle effects of NA on evoked swimming in intact animals were mimicked by either α1‐ or α2‐adrenoreceptor activation, reversibly decreasing motor burst durations and increasing their frequency. We discuss our results with reference to the known synergistic actions of NA with another aminergic neuromodulator, serotonin, and raise the possibility that these amines may actively regulate the release of one another during locomotion, in addition to their respective post‐synaptic targets in the spinal cord.
Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid‐gestation fetal sheep
Authors: Nishina Hidenori , Green Lucy R. , McGarrigle Hugh H. G. , Noakes David E. , Poston Lucilla , Hanson Mark A.
Published: September 2003

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid‐gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein‐restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid‐gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein‐restricted group fetuses (P < 0.05). Maximal relaxation (P < 0.01) and sensitivity (P < 0.05) to acetylcholine were markedly reduced in protein‐restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve, P < 0.05). The dilator response (P < 0.05) and sensitivity (P < 0.05) to the α2 agonist UK14304 was lower in protein‐, but not in globally restricted group fetuses. The response (P < 0.05) and sensitivity (P < 0.05) to the nitric oxide donor sodium nitroprusside were reduced in protein‐restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial‐dependent and ‐independent relaxation in systemic arteries from the mid‐gestation fetus. These changes may precede perturbed late‐gestation fetal and postnatal cardiovascular control.
Number and spatial distribution of nuclei in the muscle fibres of normal mice studied in vivo
Authors: Bruusgaard J. C. , Liestøl K. , Ekmark M. , Kollstad K. , Gundersen K.
Published: August 2003

We present here a new technique with which to visualize nuclei in living muscle fibres in the intact animal, involving injection of labelled DNA into single cells. This approach allowed us to determine the position of all of nuclei within a sarcolemma without labelling satellite cells. In contrast to what has been reported in tissue culture, we found that the nuclei were immobile, even when observed over several days. Nucleic density was uniform along the fibre except for the endplate and some myotendinous junctions, where the density was higher. The perijunctional region had the same number of nuclei as the rest of the fibre. In the extensor digitorum longus (EDL) muscle, the extrajunctional nuclei were elongated and precisely aligned to the long axis of the fibre. In the soleus, the nuclei were rounder and not well aligned. When comparing small and large fibres in the soleus, the number of nuclei varied approximately in proportion to cytoplasmic volume, while in the EDL the number was proportional to surface area. Statistical analysis revealed that the nuclei were not randomly distributed in either the EDL or the soleus. For each fibre, actual distributions were compared with computer simulations in which nuclei were assumed to repel each other, which optimizes the distribution of nuclei with respect to minimizing transport distances. The simulated patterns were regular, with clear row‐like structures when the density of nuclei was low. The non‐random and often row‐like distribution of nuclei observed in muscle fibres may thus reflect regulatory mechanisms whereby nuclei repel each other in order to minimize transport distances.