bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular dynamics of the DNA‐binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
Authors: Falconi M. , Santolamazza A. , Eliseo T. , de Prat‐Gay G. , Cicero D. O. , Desideri A.
Published: March 2007

Papillomaviruses are small DNA tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. The Early protein 2 is the master regulator for the virus life cycle, participating in gene transcription, DNA replication, and viral episome migration. All of these functions rely on primary target recognition by its dimeric DNA‐binding domain. In this work, we performed molecular dynamics simulations in order to gain insights into the structural dynamics of the DNA‐binding domains of two prototypic strains, human papillomavirus strain 16 and the bovine papillomavirus strain 1. The simulations underline different dynamic features in the two proteins. The human papillomavirus strain 16 domain displays a higher flexibility of the β2–β3 connecting loop in comparison with the bovine papillomavirus strain 1 domain, with a consequent effect on the DNA‐binding helices, and thus on the modulation of DNA recognition. A compact β‐barrel is found in human papillomavirus strain 16, whereas the bovine papillomavirus strain 1 protein is characterized by a loose β‐barrel with a large number of cavities filled by water, which provides great flexibility. The rigidity of the human papillomavirus strain 16 β‐barrel prevents protein deformation, and, as a consequence, deformable spacers are the preferred targets in complex formation. In contrast, in bovine papillomavirus strain 1, a more deformable β‐barrel confers greater adaptability to the protein, allowing the binding of less flexible DNA regions. The flexibility data are confirmed by the experimental NMR S2 values, which are reproduced well by calculation. This feature may provide the protein with an ability to discriminate between spacer sequences. Clearly, the deformability required for the formation of the Early protein 2 C‐terminal DNA‐binding domain–DNA complexes of various types is based not only on the rigidity of the base sequences in the DNA spacers, but also on the intrinsic deformability properties of each domain.
Chest wall kinematics during cough in healthy subjects
Authors: Lanini B. , Bianchi R. , Binazzi B. , Romagnoli I. , Pala F. , Gigliotti F. , Scano G.
Published: March 2007

Aim:  The study of kinematics of the chest wall (CW) could allow us to define the relative deflationary contribution of its compartments during fits of coughing. We hypothesized that if forces applied to the lung apposed rib cage are not commensurate with those applied to the abdomen‐apposed rib cage, cough could result in rib cage distortion.

Methods:  In 12 (five women) healthy subjects we evaluated the volumes of CW (Vcw) and its compartments: the lung apposed rib cage, the abdomen apposed rib cage and the abdomen, by optoelectronic plethysmography. The loop of volume of the lung apposed rib cage/volume of the abdomen apposed rib cage allowed the calculation of mean rib cage distortion, resulting in a dimensionless number which, when multiplied by 100, gives percentage distortion. Each subject performed voluntary single and prolonged coughing efforts at functional residual capacity (FRC) and after maximal inspiration (max). The normal level of mean distortion was set at <0.5%.

Results:  The three compartments contributed to reducing end‐expiratory Vcw during cough at FRC and prolonged maximum cough, with the latter resulting in the greatest CW deflation. Mean rib cage distortion did not differ between men and women (P > 0.1), but tended to significantly increase from single to prolonged Cough Max (1.3% ± 1.0 vs. 2.3% ± 1.6, respectively; P = 0.06).

Conclusion:  Rib cage distortion may ensue during coughing, probably as a result of uneven distribution of forces applied to the rib cage.
Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L‐arginine and antioxidants
Authors: Koeners M. P. , Racasan S. , Koomans H. A. , Joles J. A. , Braam B.
Published: March 2007

Aim:  Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life‐long blood pressure regulation.

Methods:  Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar‐Kyoto (WKY), prior to and during i.v. Nω‐nitro‐l‐arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic).

Results:  Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed.

Conclusion:  Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long‐term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation.
Francesco Paolo Cantelli
Authors: Benzi Margherita , Benzi Michele , Seneta Eugene
Published: March 2007

Francesco Paolo Cantelli made fundamental contributions to the foundations of probability theory and to the clarification of different types of probabilistic convergence. He is remembered through the Borel–Cantelli Lemma, the Glivenko–Cantelli Theorem, and Cantelli's Inequality. He also made seminal contributions to actuarial science.
Sex‐biased juvenile survival in a bird with extreme size dimorphism, the great bustard Otis tarda
Authors: A. Martín Carlos , C. Alonso Juan , A. Alonso Javier , Palacín Carlos , Magaña Marina , Martín Beatriz
Published: March 2007

We explored sex‐biased mortality patterns in a species showing the most extreme sexual dimorphism among birds, the great bustard Otis tarda. Between 1991 and 2005 we studied juvenile and immature survival in a sample of 361 great bustards radio‐tagged at two different populations in Spain, Villafáfila and Madrid. Mortality decreased with age, from high rates during the first year (0.70), to 0.10 in the second year. Using the known‐fate model in program MARK we found that monthly survival increased throughout the first year. Offspring showing higher body mass at marking, i.e. those hatched earlier in the season and those with better body condition, survived in higher proportion. This was probably related to the earlier breeding dates of more experienced mothers, as well as to the observed decrease in food availability as the season progresses. Monthly survival estimates were higher in females than in males, which suggests that juvenile males are more vulnerable to reduced food availability and other factors due to their much faster growth rates. The proportion of non‐natural deaths increased with age, and was higher in the Madrid population, where illegal hunting and collision with powerlines showed a high incidence. The male‐biased mortality found in young birds in this study explains the female‐biased population sex ratios observed in great bustard populations. The different degrees of incidence of human‐induced causes of mortality found between both populations studied suggest that such differences may contribute to the variation observed in the adult sex ratio among populations.
Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats
Authors: Hayes Shawn G. , Kindig Angela E. , Kaufman Marc P.
Published: March 2007

Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage‐gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 μg kg−1; i.a.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 μg kg−1, i.a.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 μg kg−1) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 μg kg−1) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.
Increased 5‐HT contractile response in late pregnant rat myometrium is associated with a higher density of 5‐HT2A receptors
Authors: Minosyan Tamara Y. , Lu Rong , Eghbali Mansoureh , Toro Ligia , Stefani Enrico
Published: March 2007

The 5‐hydroxytryptamine (5‐HT) type 2 receptor family is involved in multiple physiological functions in smooth muscle including proliferation, differentiation and contraction. In myometrium, 5‐HT2 receptors not only play a role in contraction but also regulate the activity of hypertrophic genes during pregnancy. Here we investigated whether 5‐HT2A receptors were up‐regulated during gestation and whether changes in expression could be correlated with changes in 5‐HT‐induced contractions in late pregnant myometrium. 5‐HT tension dose–response curves showed that 5‐HT‐induced myometrial contractility is drastically increased in late pregnancy when compared to non‐pregnant conditions. The 5‐HT maximum tension (% of 80 mm KCl contracture) increased from 17 ± 2% in non‐pregnant to 54 ± 7% in late pregnant myometrium. This tension increase took place without significant changes in the 5‐HT sensitivity as EC50 values were similar in non‐pregnant and late pregnant myometrium (0.11 ± 0.03 μm and 0.17 ± 0.02 μm, respectively). The increased 5‐HT‐induced contraction at the end of pregnancy was associated with up‐regulation of 5‐HT2A transcript (∼5‐fold) and protein (∼6‐fold) levels. These functional and biochemical studies provide evidence that myometrium remodelling during pregnancy is in part associated with up‐regulation of 5‐HT2A transcript and protein levels resulting in higher 5‐HT‐induced contractile responses. We conclude that the higher 5‐HT‐induced contractile response results from a higher density of 5‐HT2A receptors having the same properties as in non‐pregnant myometrium.
Genioglossus reflex inhibition to upper‐airway negative‐pressure stimuli during wakefulness and sleep in healthy males
Authors: Eckert Danny J. , McEvoy R. Doug , George Kate E. , Thomson Kieron J. , Catcheside Peter G.
Published: March 2007

During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative‐pressure reflex that may be diminished in sleep. Previous studies have assessed the negative‐pressure reflex using multi‐unit, rectified, moving‐time‐average EMG recordings during brief pulses of negative upper‐airway pressure. However, moving‐time averaging probably obscures the true time‐related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re‐examine the genioglossus negative‐pressure reflex in detail, without moving‐time averaging. Bipolar fine‐wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative‐pressure stimuli (∼−10 cmH2O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble‐averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26 ± 1 ms; peak amplitude 231 ± 29% of baseline) followed by a previously unreported suppression (peak latency 71 ± 4 ms; 67 ± 8% of baseline). Single‐motor‐unit activity, clearly identifiable in ∼10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26 ± 9 ms, P= 0.01). Genioglossus negative‐pressure reflex morphology and amplitude of the initial peak were maintained in non‐rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative‐pressure reflex which are differentially affected by state.
Rat α6β2δ GABAAreceptors exhibit two distinct and separable agonist affinities
Authors: Hadley Stephen H. , Amin Jahanshah
Published: March 2007

The onset of motor learning in rats coincides with exclusive expression of GABAAreceptors containing α6and δ subunits in the granule neurons of the cerebellum. This development temporally correlates with the presence of a spontaneously active chloride current through α6‐containing GABAAreceptors, known as tonic inhibition. Here we report that the coexpression of α6, β2, and δ subunits produced receptor–channels which possessed two distinct and separable states of agonist affinity, one exhibiting micromolar and the other nanomolar affinities for GABA. The high‐affinity state was associated with a significant level of spontaneous channel activity. Increasing the level of expression or the ratio of β2to α6and δ subunits increased the prevalence of the high‐affinity state. Comparative studies of α6β2δ, α1β2δ, α6β2γ2, α1β2γ2and α4β2δ receptors under equivalent levels of expression demonstrated that the significant level of spontaneous channel activity is uniquely attributable to α6β2δ receptors. The pharmacology of spontaneous channel activity arising from α6β2δ receptor expression corresponded to that of tonic inhibition. For example, GABAAreceptor antagonists, including furosemide, blocked the spontaneous current. Further, the neuroactive steroid 5α‐THDOC and classical glycine receptor agonists β‐alanine and taurine directly activated α6β2δ receptors with high potency. Specific mutation within the GABA‐dependent activation domain (βY157F) impaired both low‐ and high‐affinity components of GABA agonist activity in α6βY157Fδ receptors, but did not attenuate the spontaneous current. In comparison, a mutation located between the second and third transmembrane segments of the δ subunit (δR287M) significantly diminished the nanomolar component and the spontaneous activity. The possibility that the high affinity state of the α6β2δ receptor modulates the granule neuron activity as well as potential mechanisms affecting its expression are discussed.
Heterocyclization of (Acridin-9-yl)thiosemicarbazides with Dimethyl Acetylenedicarboxylate
Authors: Tomaščiková Jana , Imrich Ján , Danihel Ivan , Böhm Stanislav , Kristian Pavol
Published: March 2007

Two types of (acridin-9-yl)thiosemicarbazides with the acridine moiety in the thiourea part (Acr-NHCS, 10a, 10b) and hydrazine part (Acr-NHNHCS, 12a-12c) were prepared to investigate their reactions with dimethyl acetylenedicarboxylate. Five-membered thiazolidinone derivatives 15a, 15b, 19a-19c were formed; some aspects of corresponding reaction mechanisms are discussed. 1D and 2D 1H and 13C NMR spectroscopy and DFT quantum chemical calculations were used to elucidate the structure of the compounds.
Methodology for Easy Access to Large Sidewall Bis-Tröger's Bases
Authors: Havlík Martin , Král Vladimír , Dolensky Bohumil
Published: March 2007

4,6-Bis(bromomethyl)-N1,N3-bis(tert-butoxycarbonyl)benzene-1,3-diamine is introduced as a general starting compound for the preparation of bis-Tröger's base (bisTB) derivatives in excellent yield in just two steps. The synthetic sequence includes treatment of the above-mentioned protected diamine with an arylamine followed by in situ deprotection and the final bisTB-forming reaction. This sequence allows synthesis of bisTB derivatives, which are not accessible by known procedures. The described approach is a general new method for the preparation of bisTB derivatives from "troegerable" arylamines.
Relationship between the intensity of physical activity, inactivity, cardiorespiratory fitness and body composition in 7–10-year-old Dublin children
Authors: Hussey J , Bell C , Bennett K , O’Dwyer J , Gormley J
Published: March 2007

Objective:To investigate the relationships between the time spent in specific intensities of activity and inactivity, cardiorespiratory fitness and body composition in children.

Methods:A cross-sectional study was conducted in a random sample of schools. Height, weight and waist circumference were measured in 224 children aged 7–10 years. Cardiorespiratory fitness was estimated by the 20 m multistage running test, and physical activity was measured over 4 days by the RT3 (a triaxial accelerometer). Time each day spent in moderate and vigorous intensities of activity was calculated.

Results:Twelve schools agreed to participate in the study. Body composition and fitness data were obtained for 224 children and activity data for 152 children. Boys were found to take part in about twice as much vigorous and hard activity as girls (mean (95% confidence interval) 64.3 (53.2 to 75.4) min in boys compared with 37 (33.1 to 40.9) min in girls; p<0.001). In boys there was significant difference between those defined as normal, overweight and obese in the time spent in vigorous activity (p<0.05), but no such difference was found in girls. A significant negative correlation between waist circumference and time spent in vigorous activity (r = –0.31, p<0.05) was found in boys but not in girls. Time spent sedentary was positively correlated with waist circumference in boys (r = 0.33, p<0.01) but not in girls. In both boys and girls there were significant negative correlations between fitness and both body mass index (r = –0.274, p<0.001) and waist circumference (boys:r = –0.503, p<0.01; girls:r = –0.286, p<0.01).

Conclusion:In boys, body composition was inversely related to fitness and to vigorous activity and was positively related to inactivity. In girls, body composition was related to fitness but not to specific components of physical activity.
Benefit sharing: it’s time for a definition: Table 1
Authors: Schroeder D
Published: March 2007

Benefit sharing has been a recurrent theme in international debates for the past two decades. However, despite its prominence in law, medical ethics and political philosophy, the concept has never been satisfactorily defined. In this conceptual paper, a definition that combines current legal guidelines with input from ethics debates is developed. Philosophers like boxes; protective casings into which they can put concisely-defined concepts. Autonomy is the human capacity for self-determination; beneficence denotes the virtue of good deeds, coercion is the intentional threat of harm and so on. What about benefit sharing? Does the concept have a box and are the contents clearly defined? The answer to this question has to be no. The concept of benefit sharing is almost unique in that various disciplines use it regularly without precise definitions. In this article, a definition for benefit sharing is provided, to eliminate unnecessary ambiguity.
Concepts of “person” and “liberty,” and their implications to our fading notions of autonomy
Authors: Takala Tuija
Published: March 2007

It is commonly held that respect for autonomy is one of the most important principles in medical ethics. However, there are a number of interpretations as to what that respect actually entails in practice and a number of constraints have been suggested even on our self-regarding choices. These limits are often justified in the name of autonomy. In this paper, it is argued that these different interpretations can be explained and understood by looking at the discussion from the viewpoints of positive and negative liberty and the various notions of a “person” that lay beneath. It will be shown how all the appeals to positive liberty presuppose a particular value system and are therefore problematic in multicultural societies.
The unhealthy physician
Authors: Magnavita Nicola
Published: March 2007

Background:Physicians, if affected by transmissible or impairing diseases, could be hazardous for third persons.

Aim:To solve the apparent chasm between patient’s and sick worker’s rights, a consensus-building process leading to hospital-wide policies is the better alternative to individual decision making.

Conclusions:Policies have to balance the rights of the sick worker, the right of the other workers, patients and customers, and society’s expectations.
Mortality and life expectancy in relation to long-term cigarette, cigar and pipe smoking: The Zutphen Study
Authors: Streppel Martinette T , Boshuizen Hendriek C , Ocké Marga C , Kok Frans J , Kromhout Daan
Published: March 2007

Study objective:To study the effect of long-term smoking on all-cause and cause-specific mortality, and to estimate the effects of cigarette and cigar or pipe smoking on life expectancy.

Design:A long-term prospective cohort study.

Setting:Zutphen, The Netherlands.

Participants:1373 men from the Zutphen Study, born between 1900 and 1920 and studied between 1960 and 2000.

Measurements:Hazard ratios for the type of smoking, amount and duration of cigarette smoking, obtained from a time-dependent Cox regression model. Absolute health effects of smoking are expressed as differences in life expectancy and the number of disease-free years of life.

Main results:Duration of cigarette smoking was strongly associated with mortality from cardiovascular disease, lung cancer and chronic obstructive pulmonary disease, whereas both the number of cigarettes smoked as well as duration of cigarette smoking were strongly associated with all-cause mortality. Average cigarette smoking reduced the total life expectancy by 6.8 years, whereas heavy cigarette smoking reduced the total life expectancy by 8.8 years. The number of total life-years lost due to cigar or pipe smoking was 4.7 years. Moreover, cigarette smoking reduced the number of disease-free life-years by 5.8 years, and cigar or pipe smoking by 5.2 years. Stopping cigarette smoking at age 40 increased the life expectancy by 4.6 years, while the number of disease-free life-years was increased by 3.0 years.

Conclusions:Cigar or pipe smoking reduces life expectancy to a lesser extent than cigarette smoking. Both the number of cigarettes smoked and duration of smoking are strongly associated with mortality risk and the number of life-years lost. Stopping smoking after age 40 has major health benefits.
Effect of local youth-access regulations on progression to established smoking among youths in Massachusetts
Authors: Conley Thomson Carey , Hamilton William L , Siegel Michael B , Biener Lois , Rigotti Nancy A
Published: March 2007

Objective:To test whether community-level restrictions on youth access to tobacco (including both ordinances and enforcement) are associated with less smoking initiation or less progression to established smoking among adolescents.

Design:Prospective cohort study of a random sample of adolescents in Massachusetts whose smoking status was assessed by telephone interviews at baseline and 2-year follow-up, and linked to a state-wide database of town-level youth-access ordinances and enforcement practices.

Participants:A random sample of 2623 adolescents aged 12–17 years who lived in 295 towns in Massachusetts in 2001–2 and were followed in 2003–4.

Main outcome measures:The relationship between the strength of local youth access restrictions (including both ordinances and level of enforcement) and (1) never-smokers’ smoking initiation rates and (2) experimenters’ rate of progression to established smoking was tested in a multilevel analysis that accounted for town-level clustering and adjusted for potential individual, household and town-level confounders.

Results:Over 2 years, 21% of 1986 never-smokers initiated smoking and 25% of 518 experimenters became established smokers. The adjusted odds ratio (OR) for smoking initiation was 0.89 (95% CI 0.61 to 1.31) for strong versus weak youth-access policies and 0.93 (95% CI 0.67 to 1.29) for medium versus weak policies. The adjusted OR for progression to established smoking among adolescents who had experimented with smoking was 0.79 (95% CI 0.45 to 1.39) for strong versus weak local smoking restrictions and 0.85 (95% CI 0.50 to 1.45) for medium versus weak restrictions.

Conclusions:This prospective cohort study found no association between community-level youth-access restrictions and adolescents’ rate of smoking initiation or progression to established smoking over 2 years.
SEARCH FOR ULTRA-HIGH ENERGY PHOTONS USING AIR SHOWERS
Authors: RISSE MARKUS , HOMOLA PIOTR
Published: March 2007

The observation of photons with energies above 1018 eV would open a new window in cosmic-ray research, with possible impact on astrophysics, particle physics, cosmology and fundamental physics. Current and planned air shower experiments, particularly the Pierre Auger Observatory, offer an unprecedented opportunity to search for such photons and to complement efforts of multimessenger observations of the universe. We summarize motivation, achievements, and prospects of the search for ultra-high energy photons.
DOES CASSINI ALLOW ONE TO MEASURE RELATIVISTIC ORBITAL EFFECTS IN THE SATURNIAN SYSTEM OF SATELLITES?
Authors: IORIO LORENZO
Published: March 2007

In this paper we address the following question: do the recent advances in the orbit determination of the major natural satellites of Saturn obtained with the analysis of the first data sets from the Cassini spacecraft allow to detect the general relativistic gravitoelectric orbital precessions of the mean longitudes of such moons? The answer is still negative. The present-day down-track accuracy is adequate for Mimas, Enceladus, Thetys, Dione, Rhea and Titan and inadequate for Hyperion, Iapetus and Phoebe. Instead, the size of the systematic errors induced by the mismodeling in the key parameters of the Saturnian gravitational field like the even zonal harmonics Jℓ are larger than the relativistic down-track shifts by about one order of magnitude, mainly for the inner satellites like Mimas, Enceladus, Thetys, Dione, Rhea, Titan and Hyperion. Instead, Iapetus and Phoebe are not notably affected by such kind of perturbations. Moreover, the bias due to the uncertainty in Saturn's GM is larger than the relativistic down-track effects for all such moons up to two orders of magnitude (Phoebe). Thus, it would be impossible to separately analyze the mean longitudes of each satellite. Proposed linear combinations of the satellites' mean longitudes would allow to cancel out the impact of the mismodeling in the low-degree even zonal harmonics and GM, but the combined down-track errors would be larger than the combined relativistic signatures by a factor 103.
REISSNER–NORDSTRÖM SPACE–TIME IN THE TETRAD THEORY OF GRAVITATION
Authors: NASHED GAMAL G. L. , SHIRAFUJI TAKESHI
Published: March 2007

We give two classes of spherically symmetric exact solutions of the coupled gravitational and electromagnetic fields with charged source in the tetrad theory of gravitation. The first solution depends on an arbitrary function H(R,t). The second solution depends on a constant parameter η. These solutions reproduce the same metric, i.e. the Reissner–Nordström metric. If the arbitrary function which characterizes the first solution and the arbitrary constant of the second solution are set to be zero, then the two exact solutions will coincide with each other. We then calculate the energy content associated with these analytic solutions using the superpotential method. In particular, we examine whether these solutions meet the condition, which Møller required for a consistent energy–momentum complex, namely, we check whether the total four-momentum of an isolated system behaves as a four-vector under Lorentz transformations. It is then found that the arbitrary function should decrease faster than [Formula: see text] for R → ∞. It is also shown that the second exact solution meets the Møller's condition.
Reproducibility of human brain activity evoked by esophageal stimulation using functional magnetic resonance imaging
Authors: Coen Steven J. , Gregory Lloyd J. , Yágüez Lidia , Amaro Edson , Brammer Mick , Williams Steven C. R. , Aziz Qasim
Published: March 2007

Functional MRI is a popular tool for investigating central processing of visceral pain in healthy and clinical populations. Despite this, the reproducibility of the neural correlates of visceral sensation by use of functional MRI remains unclear. The aim of the present study was to address this issue. Seven healthy right-handed volunteers participated in the study. Blood oxygen level-dependent contrast images were acquired at 1.5 T while subjects received nonpainful and painful phasic balloon distensions (“on-off” block design, 10 stimuli per “on” period, 0.3 Hz) to the distal esophagus. This procedure was repeated on two further occasions to investigate reproducibility. Painful stimulation resulted in highly reproducible activation over three scanning sessions in the anterior insula, primary somatosensory cortex, and anterior cingulate cortex. A significant decrease in strength of activation occurred from session 1 to session 3 in the anterior cingulate cortex, primary somatosensory cortex, and supplementary motor cortex, which may be explained by an analogous decrease in pain ratings. Nonpainful stimulation activated similar brain regions to painful stimulation, but with greater variability in signal strength and regions of activation between scans. Painful stimulation of the esophagus produces robust activation in many brain regions. A decrease in subjective perception of pain and brain activity from the first to the final scan suggests that serial brain imaging studies may be affected by habituation. These findings indicate that for brain imaging studies that require serial scanning, development of experimental paradigms that control for the effect of habituation is necessary.
Novel localization of Rab3D in rat intestinal goblet cells and Brunner's gland acinar cells suggests a role in early Golgi trafficking
Authors: Valentijn Jack A. , van Weeren Laura , Ultee Anton , Koster Abraham J.
Published: March 2007

Rab3D is a small GTP-binding protein that associates with secretory granules of endocrine and exocrine cells. The physiological role of Rab3D remains unclear. While it has initially been implicated in the control of regulated exocytosis, recent deletion-mutation studies have suggested that Rab3D is involved in the biogenesis of secretory granules. Here, we report the unexpected finding that Rab3D also associates with early Golgi compartments in intestinal goblet cells and in Brunner's gland acinar cells. Expression of Rab3D in the intestine was demonstrated by SDS-PAGE and Western blot analysis of homogenates prepared from the rat duodenum and colon. Confocal laser scanning microscopy revealed Rab3D immunofluorescence in the Golgi area of goblet cells of the duodenum and colon and in Brunner's gland acinar cells. There was no colocalization between Rab3D and a trans-Golgi network marker, TGN-38. In contrast, Rab3D colocalized partially with a cis-Golgi marker, GM-130, and with a marker of cis-Golgi and coat protein complex I vesicles, β-COP. Strong colocalization was observed between Rab3D and the lectins Griffonia simplicifolia agglutinin II and soybean agglutinin, which have been described as markers of the medial and cis-Golgi, respectively. Rabphilin, a putative effector of Rab3D, displayed an identical pattern of Golgi localization. Incubation of colon tissue with carbamylcholine or deoxycholate to stimulate exocytosis by goblet cells caused a partial redistribution of Rab3D to the cytoplasm and mucous granule field and a concomitant transformation of the Golgi architecture. Taken together, the present data suggest that Rab3D and rabphilin may regulate the secretory pathway at a much earlier stage than what has hitherto been assumed.
Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study
Authors: Esfandyari Tuba , Camilleri Michael , Busciglio Irene , Burton Duane , Baxter Kari , Zinsmeister Alan R.
Published: March 2007

Cannabinoid receptors (CBR) are located on cholinergic neurons in the brain stem, stomach, and colon. CBR stimulation inhibits motility in rodents. Effects in humans are unclear. Dronabinol (DRO), a nonselective CBR agonist, inhibits colonic motility and sensation. The aim of this study was to compare effects of DRO and placebo (PLA) on colonic motility and sensation in healthy volunteers. Fifty-two volunteers were randomly assigned (double-blind) to a single dose of 7.5 mg DRO or PLA postoperative with concealed allocation. A balloon-manometric assembly placed into the descending colon allowed assessment of colonic compliance, motility, tone, and sensation before and 1 h after oral ingestion of medication, and during fasting, and for 1 h after 1,000-kcal meal. There was an overall significant increase in colonic compliance ( P = 0.045), a borderline effect of relaxation in fasting colonic tone ( P = 0.096), inhibition of postprandial colonic tone ( P = 0.048), and inhibition of fasting and postprandial phasic pressure ( P = 0.008 and 0.030, respectively). While DRO did not significantly alter thresholds for first gas or pain sensation, there was an increase in sensory rating for pain during random phasic distensions at all pressures tested and in both genders ( P = 0.024). In conclusion, in humans the nonselective CBR agonist, DRO, relaxes the colon and reduces postprandial colonic motility and tone. Increase in sensation ratings to distension in the presence of relaxation of the colon suggests central modulation of perception. The potential for CBR to modulate colonic motor function in diarrheal disease such as irritable bowel syndrome deserves further study.
Reduced systolic wave generation and increased peripheral wave reflection in chronic heart failure
Authors: Curtis Stephanie L. , Zambanini Andrew , Mayet Jamil , McG Thom Simon A. , Foale Rodney , Parker Kim H. , Hughes Alun D.
Published: March 2007

In human heart failure the role of wave generation by the ventricle and wave reflection by the vasculature is contentious. The aim of this study was to compare wave generation and reflection in normal subjects with patients with stable compensated heart failure. Twenty-nine normal subjects and 67 patients with heart failure (New York Heart Association class II or III) were studied by noninvasive techniques applied to the common carotid artery. Data were analyzed by wave intensity analysis to determine the nature and direction of waves during the cardiac cycle. The energy carried by an early systolic forward compression wave (S wave) generated by the left ventricle and responsible for acceleration of flow in systole was significantly reduced in subjects with heart failure ( P < 0.001), and the timing of the peak of this wave was delayed. In contrast, reflection of this wave was increased in subjects with heart failure ( P < 0.001), but the timing of reflections with respect to the S wave was unchanged. The energy of an expansion wave generated by the heart in protodiastole was unaffected by heart failure. The carotid artery wave speed and the augmentation index did not significantly differ between subjects with heart failure compared with normal individuals. The ability of the left ventricle to generate a forward compression wave is markedly impaired in heart failure. Increased wave reflection serves to maintain systolic blood pressure but also places an additional load on cardiac function in heart failure.
Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia
Authors: Choo-Wing Rayman , Nedrelow Jonathan H. , Homer Robert J. , Elias Jack A. , Bhandari Vineet
Published: March 2007

Our previous work has shown that adult mice with overexpression of IL-6 and IL-13 in the lung have enhanced survival in hyperoxia associated with reduced hyperoxia-induced lung injury and cell death. We hypothesized that there are developmental differences in these responses in the adult vs. the newborn (NB) animal, and these responses have clinical relevance in the human NB. We compared the responses to 100% O2 of NB IL-6 and IL-13 transgenic mice with wild-type littermate controls by evaluating mortality, lung tissue TUNEL staining, and mRNA expression using RT-PCR. We used ELISA to measure IL-6 levels in tracheal aspirates from human neonates. Our results show that, in contrast to the cytoprotective effects in mature mice, IL-6 caused significantly increased mortality, DNA injury, caspases, cell death regulator and angiogenic factor expression in hyperoxia in the NB. Furthermore, tracheal aspirate levels of IL-6 were significantly increased in premature neonates with respiratory distress syndrome who had an adverse outcome (bronchopulmonary dysplasia/death). In contrast to the protective effects in adults, there was no survival advantage to the NB IL-13 mice in hyperoxia. These findings imply that caution should be exercised in extrapolating results from the adult to the NB.
Role of ventrolateral medulla in generating the 10-Hz rhythm in sympathetic nerve discharge
Authors: Barman Susan M. , Gebber Gerard L.
Published: March 2007

We recorded changes in right inferior cardiac and either left inferior cardiac or left vertebral sympathetic nerve discharge (SND) produced by unilateral microinjections of GABA-A and excitatory amino acid (EAA) receptor antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Unilateral microinjections of GABA-A receptor antagonists, SR-95531 or bicuculline, into single tracks in VLM anywhere between 1 and 5 mm rostral to the obex eliminated or markedly reduced 10-Hz power in SND on both sides of the body. Low-frequency components (<6 Hz) of SND were unaffected. Complete blockade of the 10-Hz rhythm occurred with a dose of SR-95531 as low as 6.25 pmol in a 50-nl volume. Unilateral microinjections of the nonselective EAA receptor antagonist, kynurenate (KYN; 7.5 nmol), into the caudal or rostral VLM significantly reduced, but did not eliminate, 10-Hz SND ipsilateral to the injection sites, while 10-Hz SND contralateral to the injection sites was not significantly changed. These observations suggest that 1) GABAergic transmission in VLM is critical for generation of the 10-Hz rhythm, 2) the caudal and rostral portions of VLM act together to generate the 10-Hz rhythm, and 3) 10-Hz rhythm generation depends, at least in part, on tonic or phasic excitatory drive to GABAergic interneurons in caudal VLM and presympathetic neurons in rostral VLM. The data also suggest that pathways interconnecting the two halves of the brain stem play an important role in promoting 10-Hz rhythm generation.
Effects of temperature on anoxic submergence: skeletal buffering, lactate distribution, and glycogen utilization in the turtle,Trachemys scripta
Authors: Warren Daniel E. , Jackson Donald C.
Published: March 2007

To test the hypothesis that submergence temperature affects the distribution of the lactate load and glycogen utilization during anoxia in turtles, we sampled a variety of tissues after 7 days, 24 h, and 4 h of anoxic submergence at 5, 15, and 25°C, respectively. These anoxic durations were chosen because we found that they produced similar decreases in plasma HCO3−(∼18–22 meq/l). The sampled tissues included ventricle, liver, small intestine, carapace, and the following muscles: flexor digitorum longus, retrahens capitis, iliofibularis, and pectoralis. Shell and skeleton sequestered 41.9, 34.1, and 26.1% of the estimated lactate load at 5, 15, and 25°C. The changes in plasma Ca2+and Mg2+, relative to the estimated lactate load, decreased with increased temperature, indicating greater buffer release from bone at colder temperatures. Tissue lactate contents, relative to plasma lactate, increased with the temperature of the submergence. Glucose mobilization and tissue glycogen utilization were more pronounced at 15 and 25°C than at 5°C. We conclude that, in slider turtles, the ability of the mineralized tissue to participate in the buffering of lactic acid during anoxia is inversely related to temperature, causing the lactate burden to shift to the tissues at warmer temperatures. Muscles utilize glycogen during anoxia more at warmer temperatures.
Sternomastoid, rib cage, and expiratory muscle activity during weaning failure
Authors: Parthasarathy Sairam , Jubran Amal , Laghi Franco , Tobin Martin J.
Published: March 2007

We hypothesized that patients who fail weaning from mechanical ventilation recruit their inspiratory rib cage muscles sooner than they recruit their expiratory muscles, and that rib cage muscle recruitment is accompanied by recruitment of sternomastoid muscles. Accordingly, we measured sternomastoid electrical activity and changes in esophageal (ΔPes) and gastric pressure (ΔPga) in 11 weaning-failure and 8 weaning-success patients. At the start of trial, failure patients exhibited a higher ΔPga-to-ΔPes ratio than did success patients ( P = 0.05), whereas expiratory rise in Pga was equivalent in the two groups. Between the start and end of the trial, failure patients developed additional increases in ΔPga-to-ΔPes ratio ( P < 0.0014) and the expiratory rise in Pga also increased ( P < 0.004). At the start of trial, sternomastoid activity was present in 8 of 11 failure patients contrasted with 1 of 8 success patients. Over the course of the trial, sternomastoid activity increased by 53.0 ± 9.3% in the failure patients ( P = 0.0005), whereas it did not change in the success patients. Failure patients recruited their respiratory muscles in a sequential manner. The sequence began with activity of diaphragm and greater-than-normal activity of inspiratory rib cage muscles; recruitment of sternomastoids and rib cage muscles approached near maximum within 4 min of trial commencement; expiratory muscles were recruited slowest of all. In conclusion, not only is activity of the inspiratory rib cage muscles increased during a failed weaning trial, but respiratory centers also recruit sternomastoid and expiratory muscles. Extradiaphragmatic muscle recruitment may be a mechanism for offsetting the effects of increased load on a weak diaphragm.
Mast cells can modulate leukocyte accumulation and skeletal muscle function following hindlimb unloading
Authors: Dumont Nicolas , Lepage Katherine , Côté Claude H. , Frenette Jérôme
Published: March 2007

Rodent hindlimb suspension is widely used to induce inflammation and muscle impairment. We set out to define the role of mast cells in neutrophil and macrophage recruitment and muscle recovery after unloading-reloading. We hypothesized that mechanical perturbation would stimulate release of proinflammatory substances by mast cells, which would influence leukocyte recruitment and muscle function. Rats were suspended for 10 days and injected with a mast cell inhibitor (cromolyn) or stimulator (compound 48/80) or a placebo before reloading. Leukocyte accumulation and muscle function were assessed using immunohistological staining and measurements of contractile properties in vitro. Our results showed that mechanical loading activated mast cells, thereby influencing leukocyte recruitment in the early reloading periods. Indeed, the inhibition of mast cell degranulation significantly reduced the number of neutrophil cell profiles in reloaded soleus muscle, whereas mast cell activation provoked a significant increase in the number of neutrophil cell profiles in uninjured muscle. However, the inhibition of mast cell degranulation also led to a significant increase in the number of ED1+macrophage cell profiles. These perturbations in the inflammatory response caused by mast cell inhibition induced a short protective effect on the loss of muscle force after 1 day of reloading but delayed the return to the normal contractile properties of muscles after 14 days of reloading. These results indicate that mechanical loading can induce mast cell degranulation, which can influence leukocyte influx and muscle function, and also highlighted the possibility that leukocytes may play a dual role in skeletal muscles.
Adjuvant Radiotherapy after Radical Prostatectomy: Indications, Results and Side Effects
Authors: Bottke Dirk , Wiegel Thomas
Published: March 2007

Background: Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate-specific antigen (PSA) level as a sign of local and/or systemic tumor progression. Apart from a large number of retrospective investigations, available results are present only from three randomized studies which have either been completely published or are only in abstract form. Results: For pT3 prostate carcinomas the data from the three randomized studies agree, showing an around 20% reduced biochemical progression rate after 4–5 years. With these data the results of numerous retrospective studies have been confirmed. The majority of the authors use total doses of 60 Gy with single doses of 2 Gy. From one randomized study an increased local control rate is proposed as the basis for the extended freedom from biochemical progression. The rate of acute and late side effects after three-dimensional radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data for pT2 prostate carcinomas with positive margins are worse. Here controversy exists, and further investigations are required. In principle, however, adjuvant radiotherapy seems reasonable also for pT2 carcinomas with positive margins (determined by bNED – no biochemical evidence of disease). Conclusions: The effectiveness of adjuvant radiotherapy for patients with pT3 tumors and positive margins with and without detectable PSA levels is discussed. A survival advantage has not been demonstrated to date. For patients with positive margins in organ-limited prostate carcinomas (pT2 R1) randomized studies are recommended. It is unclear whether adjuvant radiotherapy is superior to radiotherapy for PSA levels increasing from the undetectable range after radical prostatectomy. To answer this question randomized studies are needed.