bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular oxygen sensing: detection of novel candidates by proteomics and organ culture
Authors: Thorne George D. , Hilliard George M. , Paul Richard J.
Published: January 2004

We have shown that the specific inhibition of hypoxia-induced relaxation by organ culture in porcine coronary arteries can be mimicked by treatment of control vessels with the protein synthesis inhibitor, cycloheximide. We hypothesize that organ culture of vascular smooth muscle results in the decreased expression of proteins that are critical for vascular oxygen sensing. Using two-dimensional gel electrophoresis and mass spectroscopy, we identified such candidate proteins. The expressions of the smooth muscle-specific protein, SM22, and tropomyosin are decreased after 24 h in organ culture. These results were confirmed by Western blot analysis. Other smooth muscle proteins (actin and calponin) exhibited little change. We also demonstrate a 50% downregulation in the small G protein, Rho, a potent modulator of Ca2+-independent force. These results indicate that organ culture preferentially inhibits the expression of certain smooth muscle proteins. This change in protein expression after organ culture correlates with the specific inhibition of hypoxic vasorelaxation. These results provide novel target pathways for investigation that are potentially important for vascular oxygen sensing.
Whole-body hypoxic preconditioning protects mice against acute hypoxia by improving lung function
Authors: Zhang Shelley X. L. , Miller James J. , Gozal David , Wang Yang
Published: January 2004

Survival in severe hypoxia such as occurs in high altitude requires previous acclimatization, which is acquired over a period of days to weeks. It was unknown whether intrinsic mechanisms existed that could be rapidly induced and could exert immediate protection on unacclimatized individuals against acute hypoxia. We found that mice pretreated with whole-body hypoxic preconditioning (WHPC, 6 cycles of 10-min hypoxia-10-min normoxia) survived significantly longer than control animals when exposed to lethal hypoxia (5% O2, survival time of 33.2 ± 6.1 min vs. controls at 13.8 ± 1.2 min, n = 10, P < 0.005). This protective mechanism became operative shortly after WHPC and remained effective for at least 8 h. Accordingly, mice subjected to WHPC demonstrated improved gas exchange when exposed to sublethal hypoxia (7% O2, arterial blood Po2 of 49.9 ± 4.2 vs. controls at 39.7 ± 3.6 Torr, n = 6, P < 0.05), reduced formation of pulmonary edema (increase in lung water of 0.491 ± 0.111 vs. controls at 0.894 ± 0.113 mg/mg dry tissue, n = 10, P < 0.02), and decreased pulmonary vascular permeability (lung lavage albumin of 7.63 ± 0.63 vs. controls at 18.24 ± 3.39 mg/dl, n = 6–10, P < 0.025). In addition, the severity of cerebral edema caused by exposure to sublethal hypoxia was also reduced after WHPC (increase in brain water of 0.254 ± 0.052 vs. controls at 0.491 ± 0.034 mg/mg dry tissue, n = 10, P < 0.01). Thus WHPC protects unacclimatized mice against acute and otherwise lethal hypoxia, and this protection involves preservation of vital organ functions.
Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle
Authors: Kuo Chia-Hua , Hwang Hyonson , Lee Man-Cheong , Castle Arthur L. , Ivy John L.
Published: January 2004

The purpose of this study was to investigate the role of insulin on skeletal muscle GLUT-4 protein expression and glycogen storage after postexercise carbohydrate supplementation. Male Sprague-Dawley rats were randomly assigned to one of six treatment groups: sedentary control (Con), Con with streptozocin (Stz/C), immediately postexercise (Ex0), Ex0 with Stz (Stz/Ex0), 5-h postexercise (Ex5), and Ex5 with Stz (Stz/Ex5). Rats were exercised by swimming (2 bouts of 3 h) and carbohydrate supplemented immediately after each exercise session by glucose intubation (1 ml of a 50% wt/vol). Stz was administered 72-h before exercise, which resulted in hyperglycemia and elimination of the insulin response to the carbohydrate supplement. GLUT-4 protein of Ex0 rats was 30% above Con in fast-twitch (FT) red and 21% above Con in FT white muscle. In Ex5, GLUT-4 protein was 52% above Con in FT red and 47% above Con in FT white muscle. Muscle glycogen in FT red and white muscle was also increased above Con in Ex5 rats. Neither GLUT-4 protein nor muscle glycogen was increased above Con in Stz/Ex0 or Stz/Ex5 rats. GLUT-4 mRNA in FT red muscle of Ex0 rats was 61% above Con but only 33% above Con in Ex5 rats. GLUT-4 mRNA in FT red muscle of Stz/C and Stz/Ex0 rats was similar but significantly elevated in Ex5/Stz rats. These results suggest that insulin is essential for the increase in GLUT-4 protein expression following postexercise carbohydrate supplementation.
Oxygen-sensing neurons in the central nervous system
Authors: Neubauer Judith A. , Sunderram Jagadeeshan
Published: January 2004

This mini-review summarizes the present knowledge regarding central oxygen-chemosensitive sites with special emphasis on their function in regulating changes in cardiovascular and respiratory responses. These oxygen-chemosensitive sites are distributed throughout the brain stem from the thalamus to the medulla and may form an oxygen-chemosensitive network. The ultimate effect on respiratory or sympathetic activity presumably depends on the specific neural projections from each of these brain stem oxygen-sensitive regions as well as on the developmental age of the animal. Little is known regarding the cellular mechanisms involved in the chemotransduction process of the central oxygen sensors. The limited information available suggests some conservation of mechanisms used by other oxygen-sensing systems, e.g., carotid body glomus cells and pulmonary vascular smooth muscle cells. However, major gaps exist in our understanding of the specific ion channels and oxygen sensors required for transducing central hypoxia by these central oxygen-sensitive neurons. Adaptation of these central oxygen-sensitive neurons during chronic or intermittent hypoxia likely contributes to responses in both physiological conditions (ascent to high altitude, hypoxic conditioning) and clinical conditions (heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, hypoventilation syndromes). This review underscores the lack of knowledge about central oxygen chemosensors and highlights real opportunities for future research.
Functional genomics approach to hypoxia signaling
Authors: Seta Karen A. , Millhorn David E.
Published: January 2004

Mammalian cells require a constant supply of oxygen to maintain energy balance, and sustained hypoxia can result in cell death. It is therefore not surprising that sophisticated adaptive mechanisms have evolved that enhance cell survival during hypoxia. During the past few years, there have been a growing number of reports on hypoxia-induced transcription of specific genes. In this review, we describe a unique experimental approach that utilizes focused cDNA libraries coupled to microarray analyses to identify hypoxia-responsive signal transduction pathways and genes that confer the hypoxia-tolerant phenotype. We have used the subtractive suppression hybridization (SSH) method to create a cDNA library enriched in hypoxia-regulated genes in oxygen-sensing pheochromocytoma cells and have used this library to create microarrays that allow us to examine hundreds of genes at a time. This library contains over 300 genes and expressed sequence tags upregulated by hypoxia, including tyrosine hydroxylase, vascular endothelial growth factor, and junB. Hypoxic regulation of these and other genes in the library has been confirmed by microarray, Northern blot, and real-time PCR analyses. Coupling focused SSH libraries with microarray analyses allows one to specifically study genes relevant to a phenotype of interest while reducing much of the biological noise associated with these types of studies. When used in conjunction with high-throughput, dye-based assays for cell survival and apoptosis, this approach offers a rapid method for discovering validated therapeutic targets for the treatment of cardiovascular disease, stroke, and tumors.
Muscle activity and aging affect myosin structural distribution and force generation in rat fibers
Authors: Lowe Dawn A. , Warren Gordon L. , Snow LeAnn M. , Thompson LaDora V. , Thomas David D.
Published: January 2004

The purpose of this study was to determine whether increased muscle activity could reverse myosin structural alterations that occur in aged rat muscle and whether those alterations could be induced in young rat muscle by decreased activity. Semimembranosus muscle activity was increased by electrical stimulation (200-ms trains, 154 Hz, 5 V) through a nerve cuff on the tibial branch of the ischiatic nerve. The protocol consisted of 5 sets of 6-10 maximal isometric contractions performed twice per week for 4 or 8-10 wk. Decreased muscle activity was induced by denervation of the semimembranosus muscle for 2 or 4 wk. Semimembranosus fibers were then studied for Ca2+-activated force generation. Fibers were also spin labeled on the myosin catalytic domain and studied using electron paramagnetic resonance (EPR) spectroscopy to assess myosin structural distribution. Increased muscle activity for 4 and 8-10 wk in ∼32-mo-old rats resulted in -16 and +4% changes in specific tension, respectively ( P < 0.01). EPR spectra showed that the fraction of myosin heads in the strong-binding structural state during contraction was reduced at 4 wk (0.241 ± 0.020 vs. 0.269 ± 0.018, P = 0.046) but returned to normal by 8-10 wk ( P = 0.67). Decreased muscle activity for 2 and 4 wk in ∼9-mo-old rats resulted in 23 and 34% reductions, respectively, in specific tension; EPR spectra showed 16 and 35% decreases in strong-binding myosin ( P < 0.01). These data support the hypothesis that changes in muscle activity affect muscle strength, at least in part through alterations in myosin structure and function.
Model of forced expiratory flows and airway geometry in infants
Authors: Lambert Rodney K. , Castile Robert G. , Tepper Robert S.
Published: January 2004

Early measurements of autopsied lungs from infants, children, and adults suggested that the ratio of peripheral to central airway resistance was higher in infants than older children and adults. Recent measurements of forced expiration suggest that infants have high flows relative to lung volume. We employed a computational model of forced expiratory flow along with physiological and anatomic data to evaluate whether the infant lung is a uniformly scaled-down version of the adult lung. First, we uniformly scaled an existing computational model of adult forced expiration to estimate forced expiratory flows (FEF) and density dependence for an 18-mo-old infant. The values obtained for FEF and density dependence were significantly lower than those reported for healthy 18-mo-old infants. Next, we modified the model for the infant lung to reproduce standard indexes of expiratory flow [forced expiratory volume in 0.5 s (FEV0.5), FEFs after exhalation of 50 and 75% forced vital capacity, FEF between 25 and 75% expired volume] for this age group. The airway sizes obtained for the infant lung model that produced accurate physiological measurements were similar to anatomic data available for this age and larger than those in the scaled model. Our findings indicate that the airways in the infant lung model differ from those in the scaled model, i.e., middle and peripheral airway sizes are larger than result from uniform downscaling of the adult lung model. We show that the infant lung model can be made to reproduce individual flow-volume curves by adjusting lumen area generation by generation.
Functional magnetic resonance signal changes in neural structures to baroreceptor reflex activation
Authors: Henderson Luke A. , Richard Chris A. , Macey Paul M. , Runquist Matthew L. , Yu Pearl L. , Galons Jean-Philippe , Harper Ronald M.
Published: January 2004

The sequence of neural responses to exogenous arterial pressure manipulation remains unclear, especially for extramedullary sites. We used functional magnetic resonance imaging procedures to visualize neural responses during pressor (phenylephrine) and depressor (sodium nitroprusside) challenges in seven isoflurane-anesthetized adult cats. Depressor challenges produced signal-intensity declines in multiple cardiovascular-related sites in the medulla, including the nucleus tractus solitarius, and caudal and rostral ventrolateral medulla. Signal decreases also emerged in the cerebellar vermis, inferior olive, dorsolateral pons, and right insula. Rostral sites, such as the amygdala and hypothalamus, increased signal intensity as arterial pressure declined. In contrast, arterial pressure elevation elicited smaller signal increases in medullary regions, the dorsolateral pons, and the right insula and signal declines in regions of the hypothalamus, with no change in deep cerebellar areas. Responses to both pressor and depressor challenges were typically lateralized. In a subset of animals, barodenervation resulted in rises and falls of blood pressure that were comparable to these resulting from the pharmacological challenges but different regional neural responses, indicating that the regional signal intensity responses did not derive from global perfusion effects but from baroreceptor mediation of central mechanisms. The findings demonstrate widespread lateralized distribution of neural sites responsive to blood pressure manipulation. The distribution and time course of neural responses follow patterns associated with early and late compensatory reactions.
Inhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat muscles
Authors: Haddad Fadia , Adams Gregory R.
Published: January 2004

Insulin-like growth factor-I (IGF-I) has been shown to stimulate a hypertrophy response in skeletal muscles in vivo. In vitro studies have delineated two primary intracellular pathways that appear to mediate the effects of IGF-I in skeletal muscle: the Ras-ERK pathway and the phosphoinositide-3 kinase pathway. In vitro, the Ras pathway appears to regulate the mitogenic effects of IGF-I signaling, whereas the phosphoinositide-3 kinase pathway is associated with cellular differentiation. On the basis of the results from in vitro studies, we hypothesized that the coinfusion of both IGF-I and an inhibitor of the Ras pathway would result in some increase in muscle protein but an inhibition of cell proliferation. Our results show that 14 days of coinfusion of MAPK/ERK kinase inhibitor PD-098059 (PD) limited the phosphorylation of ERK and prevented IGF-I induced increases in protein (18%, P < 0.05 vs. 7%, not significant) or myofibrillar protein (23%, P < 0.01 vs. 5%, not significant). However, there were similar increases in indicators of cell proliferation (e.g., total DNA, 50 and 52%, P < 0.001) in both the IGF- and IGF+PD-infused muscles. The most notable impact on IGF-I signaling was a significant blunting of IGF-I induced increase in S6K1 phosphorylation by PD-98059 coinfusion (∼5-fold, P < 0.001 vs. 3-fold, P < 0.01). These results suggest that there are interactions between the various pathways down stream of the IGF-I receptor that may behave differently in vivo than in myogenic cell lines in vitro.
Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons
Authors: Dean Jay B. , Mulkey Daniel K. , Henderson Richard A. , Potter Stephanie J. , Putnam Robert W.
Published: January 2004

Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2and reactive O2species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.
Fatigability of the elbow flexor muscles for a sustained submaximal contraction is similar in men and women matched for strength
Authors: Hunter Sandra K. , Critchlow Ashley , Shin In-Sik , Enoka Roger M.
Published: January 2004

The purpose of this study was to compare the time to task failure for a submaximal fatiguing contraction sustained with the elbow flexor muscles by men and women who were matched for strength ( n = 20, 18-35 yr). The maximal torque exerted at the wrist was similar for the men and women [64.5 ± 8.7 (SD) vs. 64.5 ± 8.3 N·m; P > 0.05], which meant that the average torque exerted during the fatiguing contraction [20% of maximum voluntary contraction (MVC)] was similar for the two sexes. The time to task failure was similar for these strength-matched men and women (819 ± 306 vs. 864 ± 391 s; P > 0.05). The mean arterial pressure was similar at the beginning of the contraction for men (97 ± 12 mmHg) and women (96 ± 15 mmHg; P > 0.05) and at task failure (134 ± 18 vs. 126 ± 26 mmHg; P > 0.05, respectively). Furthermore, the increases in heart rate, torque fluctuations, and rating of perceived exertion during the fatiguing contraction were similar for the two sexes. However, the electromyogram (EMG) activity differed for the men and women: the rate of increase in the average of the rectified EMG (% peak MVC) for all the elbow flexor muscles was less for the women compared with the men ( P < 0.05). Furthermore, the bursts of EMG activity for the elbow flexor muscles increased toward exhaustion for all subjects but at a greater rate for the women compared with the men ( P < 0.05). The results indicate that strength-matched men and women experienced similar levels of muscle fatigue and cardiovascular adjustments during a sustained low-force isometric contraction, despite differences in the EMG activity for the two groups of subjects.
Autonomic microganglion cells: a source of acetylcholine in the rat carotid body
Authors: Gauda Estelle B. , Cooper Reed , Johnson Shereé M. , McLemore Gabrielle L. , Marshall Cathleen
Published: January 2004

Hypoxic chemosensitivity of peripheral arterial chemoreceptors and the ventilatory response to O2 deprivation increases with postnatal development. Multiple putative neurotransmitters, which are synthesized in the carotid body (CB), are thought to mediate signals generated by hypoxia. Acetylcholine (ACh) is believed to be a major excitatory neurotransmitter participating in hypoxic chemosensitivity. However, it is not known whether ACh originates from type I cells in the CB. In these studies, we tested the hypothesis that choline acetyltransferase (ChAT) and vesicular ACh transporter (VAChT) mRNAs are expressed in the CB and that mRNA levels would increase with postnatal maturation or exposure to hypoxia. Semiquantitative in situ hybridization histochemistry and immunohistochemistry were used to localize cholinergic markers within neurons and cells of the rat CB, the nodose-petrosal-jugular ganglion complex, and the superior cervical ganglion up to postnatal day 28. We show that the pattern of distribution, in tissue sections, is similar for both ACh markers; however, the level of VAChT mRNA is uniformly greater than that of ChAT. VAChT mRNA and immunoreactivity are detected abundantly in the nodose-petrosal-jugular ganglion complex in a number of microganglion cells embedded in nerve fibers innervating the CB for all postnatal groups, whereas ChAT mRNA is detected in only a few of these cells. Contrary to our hypothesis, postnatal maturation caused a reduction in ACh trait expression, whereas hypoxic exposure did not induce the upregulation of VAChT and ChAT mRNA levels in the CB, microganglion, or within the ganglion complex. The present findings indicate that the source of ACh in the CB is likely within autonomic microganglion cells and cholinergic nerve terminals.
Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5′ AMP-activated protein kinase phosphorylation
Authors: Kim Junghoon , Solis Raquel S. , Arias Edward B. , Cartee Gregory D.
Published: January 2004

Exercise enhances insulin-stimulated glucose transport (GT) in skeletal muscle. Evidence suggests that 5′ AMP-activated protein kinase (AMPK) and glycogen may be important for enhanced insulin sensitivity. Our goals were to investigate the effect of various in situ muscle contraction protocols on insulin-stimulated GT and assess the relationship of contraction-induced changes in AMPK and glycogen with postcontraction improvement in insulin-stimulated GT. Rats were anesthetized, both ulnar nerves were exposed, and one nerve was electrically stimulated to contract forelimb muscles. We performed a series of five experiments, sequentially varying only one contraction parameter (train duration, train rate, pulse frequency, number of 5-min bouts, or pulse duration) while holding the others constant. Both epitrochlearis muscles were dissected out and incubated for 3.5 h before measurement of GT. For each contraction parameter studied, we identified an apparent threshold value that did not induce a significant increase in insulin-stimulated GT and an apparent peak value, above which there was a plateau or decline in insulin-stimulated GT. Using other rats, we evaluated muscle AMPK phosphorylation and glycogen concentration immediately postcontraction. AMPK phosphorylation and reduction in glycogen were increased compared with resting controls in each protocol, which had previously been shown to increase insulin-stimulated GT, as well as in several protocols that did not significantly increase insulin-stimulated GT. These data suggest that contraction-induced AMPK phosphorylation and decrease in glycogen may be necessary but are not sufficient for the postcontraction increase in insulin-stimulated GT in rat skeletal muscle.
Changes in regional cerebral blood flow distribution during postexercise hypotension in humans
Authors: Williamson J. W. , McColl R. , Mathews D.
Published: January 2004

This investigation compared patterns of regional cerebral blood flow (rCBF) during exercise recovery both with and without postexercise hypotension (PEH). Eight subjects were studied on 3 days with randomly assigned conditions: 1) after 30 min of rest; 2) after 30 min of moderate exercise (M-Ex) at 60-70% heart rate (HR) reserve during PEH; and 3) after 30 min of light exercise (L-Ex) at 20% HR reserve with no PEH. Data were collected for HR, mean blood pressure (MBP), and ratings of perceived exertion and relaxation, and rCBF was assessed by use of single-photon-emission computed tomography. With the use of ANOVA across conditions, there were differences ( P < 0.05; mean ± SD) from rest during exercise recovery from M-Ex (HR = +12 ± 3 beats/min; MBP = -9 ± 2 mmHg), but not from L-Ex (HR = +2 ± 2 beats/min; MBP = -2 ± 2 mmHg). After M-Ex, there were decreases ( P < 0.05) for the anterior cingulate (-6.7 ± 2%), right and left inferior thalamus (-10 ± 3%), right inferior insula (-13 ± 3%), and left inferior anterior insula (-8 ± 3%), not observed after L-Ex. There were rCBF decreases for leg sensorimotor regions after both M-Ex (-15 ± 4%) and L-Ex (-12 ± 3%) and for the left superior anterior insula (-7 ± 3% and -6 ± 3%), respectively. Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex. Findings suggest that these cerebral cortical regions, previously implicated in cardiovascular regulation during exercise, may also be involved in PEH.
Caffeine or melatonin effects on sleep and sleepiness after rapid eastward transmeridian travel
Authors: Beaumont M. , Batéjat D. , Piérard C. , Van Beers P. , Denis J. B. , Coste O. , Doireau P. , Chauffard F. , French J. , Lagarde D.
Published: January 2004

We measured the effects of slow-release caffeine (SRC) and melatonin (Mlt) on sleep and daytime sleepiness after a seven-time zone eastbound flight. In a double-blind, randomized, placebo-controlled study, each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 (D1) to D5 (0800) or 5 mg Mlt on preflight D-1 (1700), flight day D0 (1600), and from D1 to D3 (2300), or placebo (Pbo) at the same times. Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy. Compared with baseline, we found a significant rebound of slow-wave sleep on night 1 (N1) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 (Pbo) and N1–N3 (Mlt). Sleepiness was objectively increased under Pbo (D1–D6) and Mlt (D1–D3). SRC reduced sleepiness but also tended to affect sleep quality until the last drug day. In conclusion, both drugs have positive effects on some jet lag symptoms after an eastbound flight: SRC on daytime sleepiness, and Mlt on sleep.
Signal transduction by heme-containing PAS-domain proteins
Authors: Gilles-Gonzalez Marie-Alda , Gonzalez Gonzalo
Published: January 2004

The most common physiological strategy for detecting the gases oxygen, carbon monoxide, and nitric oxide is signal transduction by heme-based sensors, a broad class of modular proteins in which a heme-binding domain governs the activity of a neighboring transmitter domain. Different structures are possible for the heme-binding domains in these sensors, but, so far, the Per-ARNT-Sim motif, or PAS domain, is the one most commonly encountered. Heme-binding PAS (heme-PAS) domains can accomplish ligand-dependent switching of a variety of partner domains, including histidine kinase, phosphodiesterase, and basic helix-loop-helix (bHLH) DNA-binding modules. Proteins with heme-PAS domains occur in all kingdoms of life and are quite diverse in their physiological roles. Examples include the neuronal bHLH-PAS carbon monoxide sensor NPAS2 that is implicated in the mammalian circadian clock, the acetobacterial oxygen sensor AxPDEA1 that directs cellulose production, and the rhizobial oxygen sensor FixL, which governs nitrogen fixation. What factors determine the range of detection of these sensors? How do they transduce their signal? This review examines the recent advances in answering these questions.
Alterations in the expression of mRNAs and proteins that code for species relevant to eIF2B activity after an acute bout of resistance exercise
Authors: Kubica Neil , Kimball Scot R. , Jefferson Leonard S. , Farrell Peter A.
Published: January 2004

The focus of the study described herein was to examine the relative expression levels of mRNAs and proteins relevant to the regulation of translational initation, and hence protein synthesis, in the time course after an acute bout of resistance exercise in male Sprague-Dawley rats. Significant increases in the relative abundance of the mRNAs coding for the epsilon (33%) and gamma (26%) subunits of eukaryotic initiation factor (eIF) 2B were observed 48 h after the exercise bout. Furthermore, the mRNA coding for the delta subunit of eIF2B was also significantly increased, both 24 h (46%) and 48 h (44%) postexercise. There was a relative decrease in three eIF2Bϵ kinase mRNAs, namely sequences coding for glycogen synthase kinase 3β (49%), casein kinase I (48%), and casein kinase II (42%) 48 h into the recovery period. Additionally, there was a significant decrease in expression of the mRNAs coding for eIF2α (28% 24 h postexercise) and one of its regulatory kinases, double-stranded RNA-activated protein kinase (33% 48 h postexercise). Finally, an increase in eIF2B total protein (124%) was observed within 3 h postexercise. These results suggest that there may be rapid translational regulation of mRNAs coding for species relevant to translational initiation after an acute bout of resistance exercise. Furthermore, transcription of these mRNAs is altered further into the recovery period, and this might play a role in protein synthetic capacity on subsequent bouts of resistance exercise.
Influence of tendon slack on electromechanical delay in the human medial gastrocnemius in vivo
Authors: Muraoka Tetsuro , Muramatsu Tadashi , Fukunaga Tetsuo , Kanehisa Hiroaki
Published: January 2004

The purpose of this study was to clarify the influence of muscle-tendon complex stretch on electromechanical delay (EMD) in terms of the extent of tendon slack in the human medial gastrocnemius (MG). EMD and MG tendon length were measured at each of five ankle joint angles (-30, -20, -10, 0, and 5°: positive values for dorsiflexion) using percutaneous electrical stimulation and ultrasonography, respectively. The extent of MG tendon slack was calculated as MG tendon length shortening, standardized with MG tendon slack length obtained at the joint angle (-16° ± 5°) where the passive ankle joint torque was zero. EMD at -30° (19.2 ±2.2 ms) and -20° (17.2 ± 1.3 ms) was significantly greater than that at -10° (16.0 ±2.3 ms), 0° (15.0 ±1.4 ms), and 5° (14.8 ±1.4 ms), and at 0 and 5°, respectively. The relative EMD, normalized with the maximal EMD for each subject, decreased dependent on the extent of decrease in MG tendon slack. There were no significant differences in EMD among the joint angles (-10, 0, and 5°) where MG tendon slack was taken up. These results suggest that the extent of tendon slack is an important factor for determining EMD.
Echocardiographic assessment of age-associated changes in systolic and diastolic function of the female F344 rat heart
Authors: Boluyt Marvin O. , Converso Kimber , Hwang Hyun Seok , Mikkor Agdas , Russell Mark W.
Published: January 2004

Aging is associated with hypertrophy, dilatation, and fibrosis of the left ventricle (LV) of the heart. Advances in echocardiographic assessment have made it possible to follow changes in cardiac function in a serial, noninvasive manner. The purpose was to determine whether there is echocardiographic evidence of age-associated changes in chamber dimensions and systolic and diastolic properties of the female Fischer 344 (F344) rat heart. On the basis of previous invasive studies, it was predicted that echocardiographic assessment would detect age-associated changes in indexes of systolic and diastolic function. Rats were sedated with 1.5% isoflurane and placed in the supine position. Two-dimensional images and two-dimensionally guided M-mode, Doppler M mode, Doppler tissue, and pulsed-wave Doppler recordings were obtained from the parasternal long axis, parasternal short axis, and/or apical four-chamber views as per convention by using a 15-MHz linear array or 8-MHz phased-array transducer or a GE S10-MHz phased-array transducer. Compared with young adult 4-mo-old rats, there is a significant decrement in the resting systolic function of the LV in 30-mo-old female F344 rats as evidenced by declines in LV ejection fraction (80 ± 9 vs. 89 ± 5%; mean ± SD), fractional shortening (43 ± 9 vs. 54 ± 8%) and velocity of circumferential fiber shortening (2.43 ± 0.53 vs. 2.99 ± 0.50 circ/s). Evidence for age-associated differences in diastolic function included an increase in isovolumic relaxation time (25.0 ± 7.6 vs. 17.2 ± 4.4 ms) and decreases in the tissue Doppler peak E waves at the septal annulus and at the lateral annulus of the mitral valve. The modest changes in systolic and diastolic LV function that occur with advancing age in the female F344 rat are likely to reduce the capacity of the heart to respond to hemodynamic challenges.
Respiratory measurements of cardiac output: from elegant idea to useful test
Authors: Laszlo Gabriel
Published: January 2004

The measurement of cardiac output was first proposed by Fick, who published his equation in 1870. Fick's calculation called for the measurement of the contents of oxygen or CO2in pulmonary arterial and systemic arterial blood. These values could not be determined directly in human subjects until the acceptance of cardiac catheterization as a clinical procedure in 1940. In the meanwhile, several attempts were made to perfect respiratory methods for the indirect determination of blood-gas contents by respiratory techniques that yielded estimates of the mixed venous and pulmonary capillary gas pressures. The immediate uptake of nonresident gases can be used in a similar way to calculate cardiac output, with the added advantage that they are absent from the mixed venous blood. The fact that these procedures are safe and relatively nonintrusive makes them attractive to physiologists, pharmacologists, and sports scientists as well as to clinicians concerned with the physiopathology of the heart and lung. This paper outlines the development of these techniques, with a discussion of some of the ways in which they stimulated research into the transport of gases in the body through the alveolar membrane.
Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction
Authors: Rothenbach Patricia A. , Dahl Benny , Schwartz Jason J. , O'Keefe Grant E. , Yamamoto Masaya , Lee William M. , Horton Jureta W. , Yin Helen L. , Turnage Richard H.
Published: January 2004

Reduced plasma concentrations of the extracellular actin-binding proteins gelsolin and Gc-globulin correlate with pulmonary failure and death in humans after injury. The purpose of this study was to investigate the role of plasma gelsolin in the pathophysiology of inflammation-induced lung injury. We postulated that plasma gelsolin levels decrease at an early time point after burn injury and that the intravenous infusion of gelsolin prevents burn-induced pulmonary microvascular dysfunction. Adult Sprague-Dawley rats were randomized to undergo a 40% body surface area thermal injury (Burn) or manipulation without burn (Sham). Plasma gelsolin and Gc-globulin concentrations were determined at various times during the first 6 days of injury by Western blotting. Other animals were randomized to receive either recombinant human gelsolin (0.078, 0.78, or 7.8 mg) or albumin (7.8 mg) before and 8 h after Burn or Sham. Twenty-four hours later, pulmonary microvascular permeability was assessed by measuring the capillary filtration by use of an isolated, perfused lung model. We found that plasma gelsolin levels of burn-injured rats decreased to 10% of normal levels within 12 h and remained below normal levels for up to 6 days postinjury. Gc-globulin values also fall, but to a lesser extent and only transiently. Treatment of burned animals with intravenous infusions of recombinant human gelsolin prevented the increase in pulmonary microvascular permeability that accompanies this injury. Our findings are consistent with the hypothesis that plasma gelsolin depletion contributes to the pathophysiology of pulmonary microvascular dysfunction during inflammation.
Peroxynitrite does not impair pulmonary and systemic vascular responses
Authors: Nossaman B. D. , Dabisch P. A. , Liles J. T. , Baber S. R. , Champion H. C. , Kaye A. D. , Feng C.-J. , Anwar M. , Bivalacqua T. J. , Santiago J. A. , De Witt B. J. , Kadowitz P. J.
Published: January 2004

The effects of peroxynitrite (ONOO-) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO- decreased systemic arterial pressure, and injections of ONOO- into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO- into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO- were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO- has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO- are not dependent on cyclooxygenase product release.
Information Content of Auditory Cortical Responses to Time-Varying Acoustic Stimuli
Authors: Lu Thomas , Wang Xiaoqin
Published: January 2004

The present study explores the issue of cortical coding by spike count and timing using statistical and information theoretic methods. We have shown in previous studies that neurons in the auditory cortex of awake primates have an abundance of sustained discharges that could represent time-varying signals by temporal discharge patterns or mean firing rates. In particular, we found that a subpopulation of neurons can encode rapidly occurring sounds, such as a click train, with discharges that are not synchronized to individual stimulus events, suggesting a temporal-to-rate transformation. We investigated whether there were stimulus-specific temporal patterns embedded in these seemingly random spike times. Furthermore, we quantitatively analyzed the precision of spike timing at stimulus onset and during ongoing acoustic stimulation. The main findings are the following. 1) Temporal and rate codes may operate at separate stimulus domains or encode the same stimulus domain in parallel via different neuronal populations. 2) Spike timing was crucial to encode stimulus periodicity in “synchronized” neurons. 3) “Nonsynchronized” neurons showed little stimulus-specific spike timing information in their responses to time-varying signals. Such responses therefore represent processed (instead of preserved) information in the auditory cortex. And 4) spike timing on the occurrence of acoustic events was more precise at the first event than at successive ones and more precise with sparsely distributed events (longer time intervals between events) than with densely packed events. These results indicate that auditory cortical neurons mark sparse acoustic events (or onsets) with precise spike timing and transform rapidly occurring acoustic events into firing rate-based representations.
A Modeling Study Suggests Complementary Roles for GABAAand NMDA Receptors and the SK Channel in Regulating the Firing Pattern in Midbrain Dopamine Neurons
Authors: Komendantov Alexander O. , Komendantova Olena G. , Johnson Steven W. , Canavier Carmen C.
Published: January 2004

Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of N-methyl-d-aspartate (NMDA) and GABAAreceptors is a crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking Ca2+-activated potassium SK channels can facilitate burst firing. A multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAAreceptors as well as the modulation of the SK current on the firing activity. The simulated tonic activation of GABAAreceptors was calibrated by taking into account the difference in the electrotonic properties in vivo versus in vitro. Although NMDA-evoked currents are required for burst generation in the model, currents evoked by GABAA-receptor activation can also regulate the firing pattern. For example, the model predicts that increasing the level of NMDA receptor activation can produce excessive depolarization that prevents burst firing, but a concurrent increase in the activation of GABAAreceptors can restore burst firing. Another prediction of the model is that blocking the SK channel current in vivo will facilitate bursting, but not as robustly as blocking the GABAAreceptors.
How Are Complex Cell Properties Adapted to the Statistics of Natural Stimuli?
Authors: Körding Konrad P. , Kayser Christoph , Einhäuser Wolfgang , König Peter
Published: January 2004

Sensory areas should be adapted to the properties of their natural stimuli. What are the underlying rules that match the properties of complex cells in primary visual cortex to their natural stimuli? To address this issue, we sampled movies from a camera carried by a freely moving cat, capturing the dynamics of image motion as the animal explores an outdoor environment. We use these movie sequences as input to simulated neurons. Following the intuition that many meaningful high-level variables, e.g., identities of visible objects, do not change rapidly in natural visual stimuli, we adapt the neurons to exhibit firing rates that are stable over time. We find that simulated neurons, which have optimally stable activity, display many properties that are observed for cortical complex cells. Their response is invariant with respect to stimulus translation and reversal of contrast polarity. Furthermore, spatial frequency selectivity and the aspect ratio of the receptive field quantitatively match the experimentally observed characteristics of complex cells. Hence, the population of complex cells in the primary visual cortex can be described as forming an optimally stable representation of natural stimuli.
Response Patterns Along an Isofrequency Contour in Cat Primary Auditory Cortex (AI) to Stimuli Varying in Average and Interaural Levels
Authors: Nakamoto Kyle T. , Zhang Jiping , Kitzes Leonard M.
Published: January 2004

The topographical response of a portion of an isofrequency contour in primary cat auditory cortex (AI) to a series of monaural and binaural stimuli was studied. Responses of single neurons to monaural and a matrix of binaural characteristic frequency tones, varying in average binaural level (ABL) and interaural level differences (ILD), were recorded. The topography of responses to monaural and binaural stimuli was appreciably different. Patches of cells that responded monotonically to increments in ABL alternated with patches that responded nonmonotonically to ABL. The patches were between 0.4 and 1 mm in length along an isofrequency contour. Differences were found among monotonic patches and among nonmonotonic patches. Topographically, activated and silent populations of neurons varied with both changes in ILD and changes in ABL, suggesting that the area of responsive units may underlie the coding of sound level and sound location.
Neuronal Correlates of Face Identification in the Monkey Anterior Temporal Cortical Areas
Authors: Eifuku Satoshi , De Souza Wania C. , Tamura Ryoi , Nishijo Hisao , Ono Taketoshi
Published: January 2004

To investigate the neuronal basis underlying face identification, the activity of face neurons in the anterior superior temporal sulcus (STS) and the anterior inferior temporal gyrus (ITG) of macaque monkeys was analyzed during their performance of a face-identification task. The face space was composed by the activities of face neurons during the face-identification task, based on a multidimensional scaling (MDS) method; the face space composed by the anterior STS neurons represented facial views, whereas that composed by the anterior ITG neurons represented facial identity. The temporal correlation between the behavioral reaction time of the animal and the latency of face-related neuronal responses was also analyzed. The response latency of some of the face neurons in the anterior ITG exhibited a significant correlation with the behavioral reaction time, whereas this correlation was not significant in the anterior STS. The correlation of the latency of face-related neuronal responses in the anterior ITG with the behavioral reaction time was not found to be attributed to the correlation between the response latency and the magnitude of the neuronal responses. The present results suggest that the anterior ITG is closely related to judgments of facial identity, and that the anterior STS is closely related to analyses of incoming perceptual information; face identification in monkeys might involve interactions between the two areas.
Modularity of Motor Output Evoked By Intraspinal Microstimulation in Cats
Authors: Lemay Michel A. , Grill Warren M.
Published: January 2004

We studied the forces produced at the cat's hindpaw by microstimulation of the ipsi- and contralateral lumbar spinal cord in spinal intact α-chloralose anesthetized ( n = 3) or decerebrate ( n = 3) animals. Isometric force and EMG responses were measured at 9-12 limb configurations, with the paw attached to a force transducer and with the hip and femur fixed. The active forces elicited at different limb configurations were summarized as force fields representing the sagittal plane component of the forces produced at the paw throughout the workspace. The forces varied in amplitude over time but the orientations were stable, and the pattern of an active force field was invariant through time. The active force fields divided into four distinct types, and a few of the fields showed convergence to an equilibrium point. The fields were generally produced by coactivation of the hindlimb muscles. In addition, some of the fields were consistent with known spinal reflexes and the stimulation sites producing them were in laminae where the interneurons associated with those reflexes are known to be located. Muscle activation produced by intraspinal stimulation, as assessed by intramuscular EMG activity, was modified with limb configuration, suggesting that the responses were not fixed, but were modified by position-dependent sensory feedback. The force responses may represent basic outputs of the spinal circuitry and may be related to similar spinal primitives found in the frog and rat.
In Vitro Study of Odor-Evoked Behavior in a Terrestrial Mollusk
Authors: Inoue Tsuyoshi , Inokuma Yasuko , Watanabe Satoshi , Kirino Yutaka
Published: January 2004

To explore neural mechanisms how olfactory information is processed in the brain and finally converted into behavior, it would be useful to have isolated whole brains that include both olfactory organs and motor output. In the present study, we identified an in vitro index of odor-evoked behavior in the terrestrial mollusk Limax and also studied the modulation of this in vitro index of the behavior. We determined that shortening of the mantle muscles is one of the withdrawal responses selectively induced by aversive odors and that the shortening is mediated by a pair of parietal nerves. We also identified a motoneuron (named the posterior visceral neuron, p-VN) that projects to the parietal nerve and innervates the mantle muscles. When we applied various odors to the nose in these isolated molluscan brains, only aversive odors induced discharges in the p-VN. These results indicate that p-VN discharges can serve as an in vitro index of odor-induced aversive behavior. We also identified a novel serotonergic neuron (named the posterior cerebral serotonergic cell, p-CSC). Discharges in the p-CSC released serotonin to the tentacle ganglion (TG); serotonin in the TG then inhibited odor-induced discharges in the p-VN, the in vitro index of aversive behavior. These results suggest that the serotonergic system is involved in the regulation of approach and avoidance behavior in Limax.