bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct excitation of deep dorsal horn neurones in the rat spinal cord by the activation of postsynaptic P2X receptors
Authors: Shiokawa Hiroaki , Nakatsuka Terumasa , Furue Hidemasa , Tsuda Makoto , Katafuchi Toshihiko , Inoue Kazuhide , Yoshimura Megumu
Published: April 2006

ATP mediates somatosensory transmission in the spinal cord through the activation of P2X receptors. Nonetheless, the functional significance of postsynaptic P2X receptors in spinal deep dorsal horn neurones is still not yet well understood. Using the whole‐cell patch‐clamp technique, we investigated whether the activation of postsynaptic P2X receptors can modulate the synaptic transmission in lamina V neurones of postnatal day (P) 9–12 spinal cord slices. At a holding potential of −70 mV, ATPγS (100 μm), a nonhydrolysable ATP analogue, generated an inward current, which was resistant to tetrodotoxin (1 μm) in 61% of the lamina V neurones. The ATPγS‐induced inward current was accompanied by a significant increase in the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in the majority of lamina V neurones. The ATPγS‐induced inward current was not reproduced by P2Y receptor agonists, UTP (100 μm), UDP (100 μm), and 2‐methylthio ADP (100 μm), and it was also not affected by the addition of guanosine‐5′‐O‐(2‐thiodiphosphate) (GDPβS) into the pipette solution, thus suggesting that ionotropic P2X receptors were activated by ATPγS instead of metabotropic P2Y receptors. On the other hand, α,β‐methylene ATP (100 μm) did not change any membrane current, but instead increased the mEPSC frequency in the majority of lamina V neurones. The ATPγS‐induced inward current was suppressed by pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) (10 μm), but not by trinitrophenyl‐ATP (TNP‐ATP) (1 μm). Furthermore, we found that ATPγS (100 μm) produced a clear inward current which was observed in all lamina V neurones over P16 spinal cord slices, in contrast to P9–12. These results indicate that distinct subtypes of P2X receptors were functionally expressed at the post‐ and presynaptic sites in lamina V neurones, both of which may contribute to the hyperexcitability of lamina V in a different manner. In addition, the data relating to the developmental increase in the functional P2X receptors suggest that purinergic signalling may thus be more common in somatosensory transmission with maturation.
Negative Coulomb damping, limit cycles, and self-oscillation of the vocal folds
Authors: Fulcher Lewis P. , Scherer Ronald C. , Melnykov Artem , Gateva Vesela , Limes Mark E.
Published: April 2006

An effective one-mass model of phonation is developed. It borrows the salient features of the classic two-mass model of human speech developed by Ishizaka, Matsudaira, and Flanagan. Their model is based on the idea that the oscillating vocal folds maintain their motion by deriving energy from the flow of air through the glottis. We argue that the essence of the action of the aerodynamic forces on the vocal folds is captured by negative Coulomb damping, which acts on the oscillator to energize it. A viscous force is added to include the effects of tissue damping. The solutions to this single oscillator model show that when it is excited by negative Coulomb damping, it will reach a limit cycle. Displacements, phase portraits, and energy histories are presented for two underdamped linear oscillators. A nonlinear force is added so that the variations of the fundamental frequency and the open quotient with lung pressure are comparable to the behavior of the two-mass model.
Scaling laws at the critical point
Authors: Davatolhagh S.
Published: April 2006

There are two independent critical exponents that describe the behavior of systems near their critical point. However, at the critical point only the exponent η, which describes the decay of the correlation function, is usually discussed. We emphasize that there is a second independent exponent η′ that describes the decay of the fourth-order correlation function. The exponent η′ is related to the exponents determining the behavior of thermodynamic functions near criticality via a fluctuation-response equation for the specific heat. We also discuss a scaling law for η′.
A simple electron-positron pair production experiment
Authors: Peralta Luis
Published: April 2006

Pair production is an important photon interaction process at high energies. Its observation at photon energies available in an undergraduate laboratory is limited by the small cross section above the production threshold at 1022keV. Several experimental arrangements have been used to study pair production in targets using the photons emitted by radioactive sources. The complexity of these setups is difficult to reproduce in the undergraduate laboratory, because they use high-activity radioactive sources or complex targets and collimation systems. This note presents a simple experimental setup for observing pair production using standard radioactive gamma sources available in the undergraduate laboratory. The dependence of the production cross section on atomic number is extracted and compared with tabulated values by using different target materials.
Resource Letter PFBi-1: Physical frontiers in biology
Authors: Mielczarek Eugenie Vorburger
Published: April 2006

This Resource Letter provides a guide to the literature on physical frontiers in biology. Books and review articles are cited as well as journal articles for the following topics: cells and cellular mats; conformational dynamics/folding; electrostatics; enzymes, proteins, and molecular machines; material-biomineralization; miscellaneous topics; nanoparticles and nanobiotechnology; neuroscience; photosynthesis; quantum mechanics theory; scale and energy; spectroscopy and microscopy: experiments and instrumentation; single-molecule dynamics; and water and hydrogen-bonded solvents. A list of web resources and videotapes is also given.
A simple, low-cost demonstration of wavelength division multiplexing
Authors: Mazzolini Alexander P. , Cadusch Peter J.
Published: April 2006

Optics and photonics can be used to motivate students in physics courses at the high school, college, or university level. Many fundamental ideas and concepts can be taught by exploring wavelength division multiplexing as used in optical fiber communication systems. We describe a safe, simple, low-cost experimental apparatus that can be used to demonstrate the key concepts of wavelength division multiplexing. The apparatus can form the basis of several hands-on, active-learning activities.
The World of Non-Covalent Interactions: 2006
Authors: Hobza Pavel , Zahradník Rudolf , Müller-Dethlefs Klaus
Published: April 2006

The review focusses on the fundamental importance of non-covalent interactions in nature by illustrating specific examples from chemistry, physics and the biosciences. Laser spectroscopic methods and both ab initio and molecular modelling procedures used for the study of non-covalent interactions in molecular clusters are briefly outlined. The role of structure and geometry, stabilization energy, potential and free energy surfaces for molecular clusters is extensively discussed in the light of the most advanced ab initio computational results for the CCSD(T) method, extrapolated to the CBS limit. The most important types of non-covalent complexes are classified and several small and medium size non-covalent systems, including H-bonded and improper H-bonded complexes, nucleic acid base pairs, and peptides and proteins are discussed with some detail. Finally, we evaluate the interpretation of experimental results in comparison with state of the art theoretical models: this is illustrated for phenol...Ar, the benzene dimer and nucleic acid base pairs. A review with 270 references.
ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by neutrophils via CD18
Authors: Kodali Pratima , Wu Ping , Lahiji Parshawn A. , Brown Eric J. , Maher Jacquelyn J.
Published: April 2006

α-Naphthylisothiocyanate (ANIT) is a hepatotoxicant that causes acute cholestatic hepatitis with infiltration of neutrophils around bile ducts and necrotic hepatocytes. The objective of this study was to determine whether the β2-integrin CD18, which plays an important role in leukocyte invasion and cytotoxicity, contributes to ANIT-induced hepatic inflammation and liver injury. Mice with varying levels of leukocyte CD18 expression were treated with ANIT and monitored for hepatic neutrophil influx and liver injury over 48 h. Mice that were partially deficient in CD18 (30% of normal levels) developed periportal inflammation and widespread hepatic necrosis after ANIT treatment in a pattern identical to that in wild-type (WT) mice. In contrast, mice that completely lack CD18 (CD18 null) were resistant to ANIT toxicity. Forty-eight hours after ANIT, CD18-null mice displayed 60% lower serum alanine aminotransferase (ALT) levels and 75% less hepatic necrosis, as shown by morphometry, than WT mice. This was true despite evidence that ANIT still provoked hepatic neutrophil influx in CD18-null mice. WT mice could also be protected from ANIT-induced hepatocellular necrosis, by depleting the animals of neutrophils. Notably, neither CD18-null mice nor neutrophil-depleted WT mice exhibited any attenuation of bile duct injury or cholestasis due to ANIT. We conclude from these experiments that neutrophils invade ANIT-treated livers in a CD18-independent fashion but utilize CD18 to induce hepatocellular cytotoxicity. The results emphasize that neutrophil-mediated amplification of ANIT-induced liver injury is directed toward hepatocytes rather than cholangiocytes. In fact, the data indicate that the majority of ANIT toxicity toward hepatocytes in vivo is neutrophil driven.
Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation
Authors: Lehnert Mark , Uehara Tetsuya , Bradford Blair U. , Lind Henrik , Zhong Zhi , Brenner David A. , Marzi Ingo , Lemasters John J.
Published: April 2006

Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage. Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to endotoxin, our aim was to determine whether LBP contributes to hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer solution. Serum alanine aminotransferase (ALT) necrosis, neutrophil infiltration, and 4-hydroxynonenal by histology/cytochemistry and stress kinase activation by immunoblot analysis were then determined. ALT in wild-type mice was 2,461 ± 383 and 1,418 ± 194 IU/l (means ± SE), respectively, at 2 and 6 h after resuscitation versus sham ALT of 102 ± 6 IU/l. In LBP-deficient mice, ALT was blunted at both time points to 1,108 ± 340 and 619 ± 171 IU/l ( P < 0.05). Liver necrosis after 6 h was also attenuated from 3.5 ± 0.8% in wild-type mice to 1.3 ± 0.5% in LBP-deficient mice ( P < 0.05). After hemorrhage/resuscitation, neutrophil infiltration increased 71% more in wild-type than LBP knockout mice. Similarly, hepatic 4-hydroxynonenal staining, indicative of lipid peroxidation, decreased from 33.8 ± 4.5% in wild-type mice to 11.6 ± 1.9% in knockout mice ( P < 0.05). After hemorrhage/resuscitation, activation of MAPKs, JNK and ERK, occurred in wild-type mice, which was largely blocked in LBP-deficient mice. However, endotoxin in portal blood after resuscitation was not significantly different between wild-type and knockout mice. In conclusion, hemorrhagic shock and resuscitation to mice cause severe, LBP-mediated hepatocellular damage. An absence of LBP blunts hepatocellular injury with decreased neutrophil infiltration, oxidative stress, and c-Jun and ERK activation.
Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases
Authors: Fellet Andrea L. , Balaszczuk Ana M. , Arranz Cristina , López-Costa Juan José , Boveris Alberto , Bustamante Juanita
Published: April 2006

In autonomic-blocked rats treated with NG-nitro-l-arginine methyl ester (l-NAME, 7.5 mg/kg), heart rate increased 18% and mean arterial pressure increased 48%. Thyroidectomy, along with autonomic blockade, hampered the chronotropic response but did not modify the effect on blood pressure. After 150 min of autonomic blockade, the experimental end point, total nitric oxide (NO) production by heart NO synthases (NOS) decreased 61%: from 54 to 21 nmol NO·min−1·g heart−1. Mitochondrial NOS (mtNOS) and sarcoplasmic reticulum endothelial NOS activities decreased 74% and 52%, respectively. Mitochondria isolated from whole heart showed a well-coupled oxidative phosphorylation with high respiratory control and ADP-to-O ratios, decreased mtNOS activity (55–60%), and decreased mtNOS protein expression (70%). Immunohistochemistry with anti-inducible NOS antibody linked to gold particles localized mtNOS at the inner mitochondrial membranes. Histochemical right atrial NOS (NADPH-diaphorase) decreased 55% after heart denervation. The effects of autonomic denervation on the NO system were partially prevented by thyroidectomy performed simultaneously with autonomic blockade. Western blot analysis indicated a very rapid mtNOS protein turnover (half time = 120 min) with a process of protein expression that was upregulated by thyroidectomy and a degradation process that was downregulated by the autonomic nervous system. The observations suggest that NO-mediated pathways contribute to pacemaker heart activity, likely through the NO steady-state levels in the right atrium and the whole heart.
Central angiotensin AT1-receptor blockade affects thermoregulation and running performance in rats
Authors: Leite Laura H. R. , Lacerda Ana Cristina R. , Marubayashi Umeko , Coimbra Cândido C.
Published: April 2006

The effect of central angiotensin AT1-receptor blockade on thermoregulation in rats during exercise on a treadmill (18 m/min, 5% inclination) was investigated. Core (Tb) and skin tail temperatures were measured in rats while they were exercising until fatigue after injection of 2 μl of losartan (Los; 20 nmol, n = 4; 30 nmol, n = 4; 60 nmol, n = 7), an angiotensin II AT1-receptor antagonist, or 2 μl of 0.15 mol/l NaCl (Sal; n = 15) into the right lateral cerebral ventricle. Body heat rate (BHR), heat storage rate, threshold Tb for tail vasodilation (TTbV), time to fatigue, and workload were calculated. During exercise, the BHR and heat storage rate of Los-treated animals were, respectively, 40 and 53% higher ( P < 0.01) than in Sal-treated animals. Additionally, rats injected with Los showed an increased TTbV (38.59 ± 0.19°C for Los vs. 38.12 ± 0.1°C for Sal, P < 0.02), a higher Tb at fatigue point (39.07 ± 0.14°C Los vs. 38.66 ± 0.07°C Sal, P < 0.01), and a reduced running performance (27.29 ± 4.48 min Los vs. 52.47 ± 6.67 min Sal, P < 0.01), which was closely related to the increased BHR. Our data suggest that AT1-receptor blockade attenuates heat dissipation during exercise due to the higher TTbV, leading to a faster exercise-induced increase in Tb, thus decreasing running performance.
Individual differences in physical activity are closely associated with changes in body weight in adult female rhesus monkeys (Macaca mulatta)
Authors: Sullivan Elinor L. , Koegler Frank H. , Cameron Judy L.
Published: April 2006

The increased prevalence of overweight adults has serious health consequences. Epidemiological studies suggest an association between low activity and being overweight; however, few studies have objectively measured activity during a period of weight gain, so it is unknown whether low activity is a cause or consequence of being overweight. To determine whether individual differences in adult weight gain are linked to an individual’s activity level, we measured activity, via accelerometry, over a prolonged period (9 mo) in 18 adult female rhesus monkeys. Weight, food intake, metabolic rate, and activity were first monitored over a 3-mo period. During this period, there was mild but significant weight gain (5.5 ± 0.88%; t =−6.3, df = 17, P < 0.0001), whereas caloric intake and activity remained stable. Metabolic rate increased, as expected, with weight gain. Activity level correlated with weight gain ( r = −0.52, P = 0.04), and the most active monkeys gained less weight than the least active monkeys ( t = −2.74, df = 8, P = 0.03). Moreover, there was an eightfold difference in activity between the most and least active monkeys, and initial activity of each monkey was highly correlated with their activity after 9 mo ( r = 0.85, P < 0.0001). In contrast, food intake did not correlate with weight gain, and there was no difference in weight gain between monkeys with the highest vs. lowest caloric intake, total metabolic rate, or basal metabolic rate. We conclude that physical activity is a particularly important factor contributing to weight change in adulthood and that there are large, but stable, differences in physical activity among individuals.
IGF-1 is downregulated in experimental cancer cachexia
Authors: Costelli Paola , Muscaritoli Maurizio , Bossola Maurizio , Penna Fabio , Reffo Patrizia , Bonetto Andrea , Busquets Silvia , Bonelli Gabriella , Lopez-Soriano Francisco J. , Doglietto Giovanni Battista , Argilés Josep M. , Baccino Francesco M. , Fanelli Filippo Rossi
Published: April 2006

Cancer cachexia is characterized by skeletal muscle wasting that is mainly supported by hypercatabolism. Muscle atrophy has been suggested to depend on impaired IGF-1 signal transduction pathway. The present study has been aimed at investigating the IGF-1 system in rats bearing the AH-130 hepatoma, a well-characterized model of cachexia. IGF-1 mRNA expression in the gastrocnemius of tumor hosts progressively decreases to ∼50% of controls. By contrast, both IGF-1 receptor and insulin receptor mRNA levels increase in day 7 AH-130 hosts. IGF-1 and insulin circulating levels, as well as IGF-1 expression in the liver, are reduced. Muscle wasting in the AH-130 bearers is associated with hyperactivation of the ubiquitin-proteasome system. Consistently, the mRNA levels of ubiquitin and of the ubiquitin ligases atrogin-1 and MuRF1 are significantly increased in the gastrocnemius of day 7 AH-130 hosts. Exogenous IGF-1 administered to tumor bearers does not prevent cachexia. IGF-1 mRNA levels also have been evaluated in the gastrocnemius of AH-130 hosts treated with pentoxifylline, an inhibitor of TNF-α synthesis, alone or combined with formoterol, a β2-adrenergic agonist. Both treatments partially correct muscle atrophy without modifying IGF-1 and atrogin-1 mRNA levels, whereas MuRF1 hyperexpression is reduced by the combination of pentoxifylline with formoterol. These results demonstrate for the first time that the IGF-1 system is downregulated in cancer cachexia, although the underlying mechanism remains unknown. Moreover, no simple relation linking IGF-1 and/or atrogin-1 mRNA levels and muscle atrophy could be observed in these experimental conditions. Further studies are thus needed to clarify both issues.
Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance
Authors: Gorski Judith N. , Dunn-Meynell Ambrose A. , Hartman Thomas G. , Levin Barry E.
Published: April 2006

There is growing evidence that the postnatal environment can have a major impact on the development of obesity and insulin resistance in offspring. We postulated that cross-fostering obesity-prone offspring to lean, obesity-resistant dams would ameliorate their development of obesity and insulin resistance, while fostering lean offspring to genetically obese dams would lead them to develop obesity and insulin resistance as adults. We found that obesity-prone pups cross-fostered to obesity-resistant dams remained obese but did improve their insulin sensitivity as adults. In contrast, obesity-resistant pups cross-fostered to genetically obese dams showed a diet-induced increase in adiposity, reduced insulin sensitivity, and associated changes in hypothalamic neuropeptide, insulin, and leptin receptors, which might have contributed to their metabolic defects. There was a selective increase in insulin levels and differences in fatty acid composition of obese dam milk which might have contributed to the increased adiposity, insulin resistance, and hypothalamic changes in obesity-resistant cross-fostered offspring. These results demonstrate that postnatal factors can overcome both genetic predisposition and prenatal factors in determining the development of adiposity, insulin sensitivity, and the brain pathways that mediate these functions.
An arousing, musically enhanced bird song stimulus mediates circadian rhythm phase advances in dim light
Authors: Goel Namni
Published: April 2006

A musically enhanced bird song stimulus presented in the early subjective night phase delays human circadian rhythms. This study determined the phase-shifting effects of the same stimulus in the early subjective day. Eleven subjects (ages 18–63 yr; mean ± SD: 28.0 ± 16.6 yr) completed two 4-day laboratory sessions in constant dim light (<20 lux). They received two consecutive presentations of either a 2-h musically enhanced bird song or control stimulus from 0600 to 0800 on the second and third mornings while awake. The 4-day sessions employing either the stimulus or control were counterbalanced. Core body temperature (CBT) was collected throughout the study, and salivary melatonin was obtained every 30 min from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Dim light melatonin onset and CBT minimum circadian phase before and after stimulus or control presentation was assessed. The musically enhanced bird song stimulus produced significantly larger phase advances of the circadian melatonin (mean ± SD: 0.87 ± 0.36 vs. 0.24 ± 0.22 h) and CBT (1.08 ± 0.50 vs. 0.43 ± 0.37 h) rhythms than the control. The stimulus also decreased fatigue and total mood disturbance, suggesting arousing effects. This study shows that a musically enhanced bird song stimulus presented during the early subjective day phase advances circadian rhythms. However, it remains unclear whether the phase shifts are due directly to effects of the stimulus on the clock or are arousal- or dim light-mediated effects. This nonphotic stimulus mediates circadian resynchronization in either the phase advance or delay direction.
Acute renal response to LPS: impaired arginine production and inducible nitric oxide synthase activity
Authors: Munger Karen A. , Blantz Roland C. , Lortie Mark J.
Published: April 2006

We have previously shown in rats that lipopolysaccharide (LPS) causes both decreased renal perfusion and kidney arginine production before nitric oxide (NO) synthesis, resulting in a >30% reduction in plasma arginine. To clarify the early phase effects of LPS, we asked the following two questions: 1) is the rapid change in renal arginine production after LPS simply the result of decreased substrate (i.e., citrulline) delivery to the kidney or due to impaired uptake and conversion and 2) is the systemic production of NO limited by plasma arginine availability after LPS? Arterial and renal vein plasma was sampled at 30-min intervals from anesthetized rats with or without citrulline or arginine (2 μmol·min−1·kg−1iv) a dose with no effect on MAP, renal function, or NO production. Exogenous citrulline was quickly converted to arginine by the kidney, resulting in plasma levels similar to equimolar arginine infusion. Also, the increase in citrulline uptake resulted primarily from increased filtered load and reabsorption. In a separate series, citrulline was infused after LPS administration, verifying that citrulline uptake and conversion persists during impaired kidney function. Last, in rats given LPS, the elevation of plasma arginine had no discernable impact on mean arterial pressure, kidney function, or systemic NO production. This work demonstrates how arginine synthesis is normally “substrate limited” and explains how impaired kidney perfusion quickly results in decreased plasma arginine. However, contrary to in vitro studies, the significant reduction in extracellular arginine during the early phase response to LPS in vivo is not functionally rate limiting for NO production.
Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage
Authors: Mayr S. , Walz C. R. , Angele P. , Hernandez-Richter T. , Chaudry I. H. , Loehe F. , Jauch K. W. , Angele M. K.
Published: April 2006

Several studies indicate that cell-mediated immune responses, i.e., macrophage (MΦ) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MΦ cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 ± 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MΦ was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MΦ after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MΦ from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MΦ after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.
Role of nitric oxide in the regulation of digital pulse volume amplitude in humans
Authors: Nohria Anju , Gerhard-Herman Marie , Creager Mark A. , Hurley Shauna , Mitra Debi , Ganz Peter
Published: April 2006

Measurement of the increase in digital pulse volume amplitude (PVA) during reactive hyperemia relative to baseline (PVA-RH) is being applied widely as a convenient test of nitric oxide bioavailability. However, evidence linking digital PVA-RH to nitric oxide is currently lacking. Accordingly, we investigated whether nitric oxide is responsible for the increase in digital PVA. During reactive hyperemia, we used a peripheral arterial tonometer to record digital PVA at baseline and during reactive hyperemia. The role of nitric oxide in these responses was investigated in 19 healthy subjects by inhibiting nitric oxide synthesis with NG-nitro-l-arginine methyl ester (l-NAME). Ten subjects underwent the identical protocol with saline and five with phenylephrine, a nonspecific vasoconstrictor, instead of l-NAME. The change in digital PVA after drug administration was compared between the three groups. Relative to the response with saline (−5 ± 2%), baseline PVA was unchanged by l-NAME infusion (−10 ± 2%), but it decreased significantly with phenylephrine (−50 ± 12%; P = 0.003). PVA-RH increased slightly with saline infusion (9 ± 4%). In comparison, PVA-RH was significantly blunted by l-NAME administration (−46 ± 21%; P = 0.002) and was relatively unchanged by phenylephrine (20 ± 9%). The present study establishes a central role for nitric oxide in the augmentation of PVA during reactive hyperemia. The measurement of digital PVA-RH may indeed provide a simple means of assessing endothelial function in humans.
In Vivo Low-Density Lipoprotein Exposure Induces Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Correlated With Activator Protein-1 Expression
Authors: Verna Lynne , Ganda Chintya , Stemerman Michael B.
Published: April 2006

Objective—

We tested the hypothesis that direct native low-density lipoprotein (LDL) injection into LDL receptor–deficient (LDLR
−/−
) mice would induce the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in their aortic endothelial cells, and that transcriptional regulation of this pathway involved activator protein-1 (AP-1) but not nuclear factor κB (NF-κB).

Methods and Results—

Using tail vein injection of LDL into LDLR
−/−
mice, we were able to maintain atherogenic LDL blood levels, which induced ICAM-1 and VCAM-1 expression in their aortic endothelial cells after 24 hours. We were able to visualize and quantify this expression using immunohistochemistry and confocal microscopy. Under conditions in which ICAM-1 and VCAM-1 were expressed, the regulatory AP-1 proteins c-Fos and c-Jun were also highly expressed in the endothelial cell cytoplasm and observed within the cell nucleus. The NF-κB protein P65, although expressed in the endothelial cell cytoplasm after LDL injection, was not observed within the cell nucleus.

Conclusions—

Elevated LDL blood levels, maintained in vivo, increased the expression of the adhesion molecules ICAM-1 and VCAM-1 in aortic endothelial cells. This effect appeared to correlate with AP-1 but not NF-κB.
Differential Calcineurin/NFATc3 Activity Contributes to the
I
to
Transmural Gradient in the Mouse Heart
Authors: Rossow Charles F. , Dilly Keith W. , Santana Luis F.
Published: April 2006

Kv4 channels are differentially expressed across the mouse left ventricular free wall. Accordingly, the transient outward K
+
current (
I
to
), which is produced by Kv4 channels, is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells. However, the mechanisms underlying heterogeneous Kv4 expression in the heart are unclear. Here, we tested the hypothesis that differential [Ca
2+
]
i
and calcineurin/NFATc3 signaling in EPI and ENDO cells contributes to the gradient of
I
to
function in the mouse left ventricle. In support of this hypothesis, we found that [Ca
2+
]
i
, calcineurin, and NFAT activity were greater in ENDO than in EPI myocytes. However, the amplitude of
I
to
was the same in ENDO and EPI cells when [Ca
2+
]
i
, calcineurin, and NFAT activity were equalized. Consistent with this, we observed complete loss of
I
to
and Kv4 heterogeneity in NFATc3-null mice. Interestingly, Kv4.3, Kv4.2, and KChIP2 genes had different apparent thresholds for NFATc3-dependent suppression and were ordered as Kv4.3≈KChIP2>Kv4.2. Based on these data, we conclude that calcineurin and NFATc3 constitute a Ca
2+
-driven signaling module that contributes to the nonuniform distribution of Kv4 expression, and hence
I
to
function, in the mouse left ventricle.
Activation of Myocardial Contraction by the N-Terminal Domains of Myosin Binding Protein-C
Authors: Herron Todd J. , Rostkova Elena , Kunst Gudrun , Chaturvedi Rajiv , Gautel Mathias , Kentish Jonathan C.
Published: April 2006

Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in striated muscle sarcomeres. Its C terminus binds tightly to myosin, whereas the N terminus contains binding sites for myosin S2 and possibly for the thin filament. To study the role of the N-terminal domains of cardiac MyBP-C (cMyBP-C), we added human N-terminal peptide fragments to human and rodent skinned ventricular myocytes. At concentrations >10 μmol/L, the N-terminal C0C2 peptide activated force production in the absence of calcium (pCa 9). Force at the optimal concentration (80 μmol/L) of C0C2 was ≈60% of that in maximal Ca
2+
(pCa 4.5), but the rate constant of tension redevelopment (
k
tr
) matched or exceeded (by up to 80%) that produced by Ca
2+
alone. Experiments using different N-terminal peptides suggested that this activating effect of C0C2 resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the terminal C0 domain. At a lower concentration (1 μmol/L), exogenous C0C2 strongly sensitized cardiac myofibrils to Ca
2+
at a sarcomere length (SL) of 1.9 μm but had no significant effect at SL 2.3 μm. This differential effect caused the normal SL dependence of myofibrillar Ca
2+
sensitivity to be reduced by 80% (mouse myocytes) or abolished (human myocytes) in 1 μmol/L C0C2. These results suggest that cMyBP-C provides a regulatory pathway by which the thick filament can influence the activation of the thin filament, separately from its regulation by Ca
2+
. Furthermore, the N-terminal region of cMyBP-C can influence the SL-tension (Frank–Starling) relationship in cardiac muscle.
Atherosclerotic Plaque Macrophage Transcriptional Regulators Are Expressed in Blood and Modulated by Tristetraprolin
Authors: Patino Willmar D. , Kang Ju-Gyeong , Matoba Satoaki , Mian Omar Y. , Gochuico Bernadette R. , Hwang Paul M.
Published: April 2006

Circulating monocytes and plaque macrophages mediate inflammation in the pathogenesis of atherosclerosis. We purified these cells from patients undergoing carotid endarterectomy for advanced atherosclerosis and examined their in vivo transcriptomes using the serial analysis of gene expression (SAGE) technique. We observed striking differences in transcriptional regulators as monocytes transformed into plaque macrophages in contrast to monocytes and lung macrophages from normal subjects. Consistent with its role in moderating inflammation, tristetraprolin (TTP, ZFP36) was among the most highly expressed macrophage transcriptional regulators. Interestingly, the mRNAs of a subset of the macrophage transcriptional regulators specifically interacted with TTP, revealing a network of genes that may be important in controlling macrophage inflammatory activity. Giving functional significance to this interaction, the knockdown of TTP increased both cognate macrophage gene mRNAs and inflammatory tumor necrosis factor protein release. In contrast, transient overexpression of TTP resulted in decreased levels of the same genes supporting its role in regulating macrophage gene expression. Together, our results indicate that the in vivo gene expression analyses of cells involved in pathogenesis can provide biological insights for functional studies with potential clinical implications.
Clinical Outcome After First and Recurrent Hemorrhage in Patients With Untreated Brain Arteriovenous Malformation
Authors: Choi Jae H. , Mast Henning , Sciacca Robert R. , Hartmann Andreas , Khaw Alexander V. , Mohr Jay P. , Sacco Ralph L. , Stapf Christian
Published: April 2006

Background and Purpose—

The morbidity from spontaneous hemorrhage of untreated brain arteriovenous malformations (AVM) is not well described.

Methods—

The 241 consecutive AVM patients (mean age 37±16 years, 52% women) from the prospective Columbia AVM Databank initially presenting with hemorrhage were evaluated using the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS). From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during follow-up. For further comparisons, 84 non-AVM patients with intracerebral hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group.

Results—

In 241 AVM patients presenting with hemorrhage the median RS was 2 and the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS <2). The median time between hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM hemorrhage during follow-up resulted in no significant increase in morbidity (median RS 2,
P
=0.004; median NIHSS 3,
P
=0.322; time between hemorrhage and study evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes, parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS ≥2) than nonparenchymatous hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12;
P
<0.0001).

Conclusions—

Hemorrhage, either at initial presentation or during follow-up of untreated AVM patients appears to carry a lower morbidity than intracranial hemorrhage from other causes. These findings support a careful weighing of risks from interventional treatment and natural history.
Researching the 60-Hour Dual-Earner Workweek
Authors: Hill E. Jeffrey , Mead Nicole Timmons , Dean Lukas Ray , Hafen Dawn M. , Gadd Robyn , Palmer Alexis A. , Ferris Maria S.
Published: April 2006

This study is the first known large-scale research specifically examining the 60-hour workweek hypothesis, which proposes that the ideal for intact households with children is for both parents to participate in paid employment but with the combinedwork hours of the mother and the father not to exceed 60 hours per week. Three groups of married couples with children are compared: full-time/full-time; at least one partner part-time (60-hour); and full-time/not employed. The relationship between these arrangements and eightwork and family outcomes—job satisfaction, job flexibility, job performance, organizational commitment, work-family fit, work-to-family conflict, family-to-work conflict, and family satisfaction—is examined. The sample is from International Business Machines Corporation ( N= 3,097) and consists mostly of employees in professional positions. Sixty-hour couples report significantly greater job flexibility, improved workfamily fit, enhanced family satisfaction, and lesswork-to-family conflict. Results are discussed as they relate to the recent trend for professional mothers to leave theworkplace.
Further Examination of the Link Between Work-Family Conflict and Physical Health
Authors: Allen Tammy D. , Armstrong Jeremy
Published: April 2006

Although research consistently finds a relationship between work-family conflict and employee health, the role of health-related behaviors such as diet and exercise have been overlooked. The present research examines the links between both directions of workfamily conflict—family interference withwork (FIW) andwork interference with family (WIF)—with several health-related behaviors (physical activity, fatty food consumption, and healthy food consumption) and with multiple indicators of physical health (overall health, health disorders, and body mass). Based on a sample of 246 employed individuals, path analysis demonstrates that FIW was associated with less physical activity and with eating more high fat foods. In addition, WIF was associated with eating fewer healthy foods. Fatty food consumption related to body mass and overall health, whereas physical activity related to overall health and health disorders. The findings represent an initial step toward a better understanding of the process linkingwork-family conflict with employee physical health.
When Workers Care
Authors: Chesley Noelle , Moen Phyllis
Published: April 2006

This study analyzes longitudinal survey data on dual-earner couples ( N= 884) to assess individual- and couple-level effects of caregiving on changes in well-being. The authors draw on a life course, role context, and strategic selection theoretical framework to examine positive and negative effects of individuals' own caregiving transitions and their having a spouse engaged in caregiving on well-being. The authors find that (a) caregiving is associated with well-being declines for dual-earner women and well-being increases for dual-earner men; (b) women caregivers with flexible work arrangements report higher levels of well-being than caregivers without such arrangements, although the size of this effect is small; and (c) having a spouse involved in caregiving affects employee well-being, but in different ways for women and men.
“Uncodified Workings and Unworkable Codes”
Authors: Erk Jan
Published: April 2006

The discrepancy between the written constitution and the day-to-dayworkings of the Canadian federal system is noted by a number of observers. However, there is yet no general theory that seeks to explain why de jure constitution and de facto practice diverge from one another. This article proposes an explanation based on the ethnolinguistic social structure. The workings of the federal system are best observed in the field of public policy where the constituent linguistic/cultural communities of Canada function as default demoi, bypassing the formal structures of the federation. This process is particularly visible in education and media where identity politics find their first outlet. As a result, in the absence of formal recognition, the duality of the Canadian society tends to reveal itself through the workings of the system.
Diffusion Is No Illusion
Authors: Brinks Daniel , Coppedge Michael
Published: April 2006

This article develops and tests a specific model of the role of diffusion as a determinant of the magnitude and direction of regime change, using a database covering the world from 1972 to 1996. The authors find that countries tend to change their regimes to match the average degree of democracy or nondemocracy found among their contiguous neighbors and that countries in the U.S. sphere of influence tended to become more democratic in the period examined. They also confirm that countries tend to follow the direction in which the majority of other countries in the world are moving. Their model builds on several findings in the diffusion literature but adds methodological improvements and includes more extensive controls for other variables that have been found to affect regime change—including levels of development, presidentialism, and regional differences—offering further support for some and challenging other findings of the regime change literature.
The Meta-Analysis of Clinical Judgment Project: Fifty-Six Years of Accumulated Research on Clinical Versus Statistical Prediction
Authors: Ægisdóttir Stefanía , White Michael J. , Spengler Paul M. , Maugherman Alan S. , Anderson Linda A. , Cook Robert S. , Nichols Cassandra N. , Lampropoulos Georgios K. , Walker Blain S. , Cohen Genna , Rush Jeffrey D.
Published: April 2006

Clinical predictions made by mental health practitioners are compared with those using statistical approaches. Sixty-seven studies were identified from a comprehensive search of 56 years of research; 92 effect sizes were derived from these studies. The overall effect of clinical versus statistical prediction showed a somewhat greater accuracy for statistical methods. The most stringent sample of studies, from which 48 effect sizes were extracted, indicated a 13% increase in accuracy using statistical versus clinical methods. Several variables influenced this overall effect. Clinical and statistical prediction accuracy varied by type of prediction, the setting in which predictor data were gathered, the type of statistical formula used, and the amount of information available to the clinicians and the formulas. Recommendations are provided about when and under what conditions counseling psychologists might use statistical formulas as well as when they can rely on clinical methods. Implications for clinical judgment research and training are discussed.
Sixty-Six Years of Research on the Clinical Versus Actuarial Prediction of Violence
Authors: Hilton N. Zoe , Harris Grant T. , Rice Marnie E.
Published: April 2006

In their meta-analysis of clinical versus statistical prediction models, Ægisdóttir et al. (this issue) extended previous findings of statistical-method superiority across such variables as clinicians’ experience and familiarity with data. In this reaction, the authors are particularly interested in violence prediction, which yields the greatest support for actuarial models. In the past decade, actuarial prediction has continued to improve, but clinicians have not readily adopted these models, and new models have emerged that encourage reliance on unaided clinical judgment. Psychologists have made progress developing and disseminating actuarial risk assessments and should use the most accurate available measure suited to the task.
Should I Pack My Umbrella? Clinical Versus Statistical Prediction of Mental Health Decisions
Authors: Ægisdóttir Stefanía , Spengler Paul M. , White Michael J.
Published: April 2006

In this rejoinder, the authors respond to the insightful commentary of Strohmer and Arm, Chwalisz, and Hilton, Harris, and Rice about the meta-analysis on statistical versus clinical prediction techniques for mental health judgments. The authors address issues including the availability of statistical prediction techniques for real-life psychology applications, the development of these prediction techniques for future applications, and the training of counseling and other psychologists in using statistical prediction techniques. Many of these issues are couched in the historical debate about clinical versus statistical prediction.
Introduction to Three Cross-Regional Research Studies on Parenting Styles, Individuation, and Mental Health in Arab Societies
Authors: Dwairy Marwan , Achoui Mustafa
Published: April 2006

This is a general introduction to the series of three articles that follows. The study intended to examine cross-regional differences concerning parenting styles, adolescent-family connectedness, and mental health in eight Arab societies. Three questionnaires were administered to 2,893 Arab adolescents in eight Arab societies: Parental Authority Questionnaire, Multigenerational Interconnectedness Scale, and Psychological State Scale. The results of the analysis are presented in the following reports. The strength of our study is in the size and diversity of the sample, whereas its limitation is that all the study results are based on adolescents' self-report. To validate our results, more research is needed using other measures such as parents' self-report and observations of parents and adolescents.
Parenting Styles in Arab Societies
Authors: Dwairy Marwan , Achoui Mustafa , Abouserie Reda , Farah Adnan , Sakhleh Anaya A. , Fayad Mona , Khan Hassan K.
Published: April 2006

The Arab language version of the Parental Authority Questionnaire was administered to 2,893 Arab adolescents in eight Arab societies. Results show that all parenting styles differed across Arab societies. Cluster analysis revealed three combined parenting patterns: inconsistent (permissive and authoritarian), controlling (authoritarian and authoritative), and flexible (authoritative and permissive). The mean score of the authoritarian style was higher among males, whereas the mean score of the authoritative style was higher among females. First-born adolescents reported higher level permissive parenting than other adolescents. The effects of urbanization, parents' education, and the family economic level on parenting were minor.
Individualism and Good Works
Authors: Kemmelmeier Markus , Jambor Edina E. , Letner Joyce
Published: April 2006

Building on previous research by Allik and Realo and Conway, Ryder, Tweed, and Sokol, the present study investigates whether cultural individualism is related to greater levels of prosocial behavior toward strangers. Focusing on regional variations within the United States, the authors found individualism to be positively related to charitable giving and volunteerism such that both were more likely to occur in more individualist states. Differentiating between different types of charitable causes, the authors found that cultural individualism was primarily related to giving to and volunteering for causes that were compatible with core individualist values, whereas no such relationship was found for religious causes and nonreligious cause that did not incorporate values of individualism.