bluuebunny/crossref_metadata_2025 huggingface dataset:
Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors
Authors: Mälkiä Annika , Madrid Rodolfo , Meseguer Victor , De La Peña Elvira , Valero María , Belmonte Carlos , Viana Félix
Published: February 2007

TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of TRPM8 by cold and menthol takes place through shifts in its voltage‐activation curve, which cause the channel to open at physiological membrane potentials. By contrast, little is known about the actions of inhibitors on the function of TRPM8. We investigated the chemical and thermal modulation of TRPM8 in transfected HEK293 cells and in cold‐sensitive primary sensory neurons. We show that cold‐evoked TRPM8 responses are effectively suppressed by inhibitor compounds SKF96365, 4‐(3‐chloro‐pyridin‐2‐yl)‐piperazine‐1‐carboxylic acid (4‐tert‐butyl‐phenyl)‐amide (BCTC) and 1,10‐phenanthroline. These antagonists exert their effect by shifting the voltage dependence of TRPM8 activation towards more positive potentials. An opposite shift towards more negative potentials is achieved by the agonist menthol. Functionally, the bidirectional shift in channel gating translates into a change in the apparent temperature threshold of TRPM8‐expressing cells. Accordingly, in the presence of the antagonist compounds, the apparent response‐threshold temperature of TRPM8 is displaced towards colder temperatures, whereas menthol sensitizes the response, shifting the threshold in the opposite direction. Co‐application of agonists and antagonists produces predictable cancellation of these effects, suggesting the convergence on a common molecular process. The potential for half maximal activation of TRPM8 activation by cold was ∼140 mV more negative in native channels compared to recombinant channels, with a much higher open probability at negative membrane potentials in the former. In functional terms, this difference translates into a shift in the apparent temperature threshold for activation towards higher temperatures for native currents. This difference in voltage‐dependence readily explains the high threshold temperatures characteristic of many cold thermoreceptors. The modulation of TRPM8 activity by different chemical agents unveils an important flexibility in the temperature–response curve of TRPM8 channels and cold thermoreceptors.
In the developing rat hippocampus a tonic GABAA‐mediated conductance selectively enhances the glutamatergic drive of principal cells
Authors: Marchionni Ivan , Omrani Azar , Cherubini Enrico
Published: February 2007

In the adult hippocampus, two different forms of GABAAreceptor‐mediated inhibition have been identified: phasic and tonic. The first is due to the activation of GABAAreceptors facing the presynaptic releasing sites, whereas the second is due to the activation of receptors localized away from the synapses. Because of their high affinity and low desensitization rate, extrasynaptic receptors are persistently able to sense low concentrations of GABA. Here we show that, early in postnatal life, between postnatal day (P) 2 and P6, CA1 and CA3 pyramidal cells but not stratum radiatum interneurons, express a tonic GABAA‐mediated conductance. Block of the neuronal GABA transporter GAT‐1 slightly enhanced the persistent GABA conductance in principal cells but not in GABAergic interneurons. However, in adulthood, a tonic GABAA‐mediated conductance could be revealed in stratum radiatum interneurons, indicating that the ability of these cells to sense ambient GABA levels is developmentally regulated. Pharmacological analysis of the tonic conductance in principal cells demonstrated the involvement of β2/β3, α5 and γ2 GABAAreceptor subunits. Removal of the tonic depolarizing action of GABA with picrotoxin, reduced the excitability and the glutamatergic drive of principal cells but did not modify the excitability of stratum radiatum interneurons. The increased cell excitability and synaptic activity following the activation of extrasynaptic GABAAreceptors by ambient GABA would facilitate the induction of giant depolarizing potentials.
Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia
Authors: Button Brian , Picher Maryse , Boucher Richard C.
Published: February 2007

In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2‐purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS‐induced increase in ASL ATP concentration was sufficient to induce purinoceptor‐mediated increases in ASL height and MCC, via inhibition of epithelial Na+‐channel‐mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+‐activated chloride channels. In contrast, static, non‐oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence.
Chemical control stability in the elderly
Authors: Wellman Andrew , Malhotra Atul , Jordan Amy S. , Schory Karen , Gautam Shiva , White David P.
Published: February 2007

The prevalence of central apnoea and periodic breathing is increased in the elderly. This implies that the chemical control of breathing might become less stable with ageing. To investigate this, we measured loop gain in healthy elderly individuals using proportional assist ventilation. Loop gain is an engineering term that describes the stability of a system controlled by feedback loops, such as the respiratory control system. A loop gain close to zero indicates a stable system, whereas a loop gain close to or greater than one indicates an unstable system. Eleven healthy elderly subjects were studied with a mean ±s.d. age and body mass index (BMI) of 71 ± 5 years and 25 ± 3 kg m−2, respectively. We also studied a small group of elderly individuals with obstructive sleep apnoea (OSA) for comparison (n= 3, age 68 ± 1 years, BMI 32 ± 11 kg m−2). Comparisons were made with previously studied young individuals (age 27 ± 4 years, BMI 23 ± 1 kg m−2). We found significantly lower loop gains in the healthy elderly group (loop gain ≤ 0.25) compared with the young group (loop gain ≤ 0.47, P= 0.001). Also, we found quite low loop gains in the elderly OSA group (loop gain ≤ 0.26). We conclude that the chemical control of breathing does not become unstable with ageing and is thus an unlikely cause of central (and possibly obstructive) apnoeas in this population.
Investigation of thin filament near‐neighbour regulatory unit interactions during force development in skinned cardiac and skeletal muscle
Authors: Gillis Todd E. , Martyn Donald A. , Rivera Anthony J. , Regnier Michael
Published: February 2007

Ca2+‐dependent activation of striated muscle involves cooperative interactions of cross‐bridges and thin filament regulatory proteins. We investigated how interactions between individual structural regulatory units (RUs; 1 tropomyosin, 1 troponin, 7 actins) influence the level and rate of demembranated (skinned) cardiac muscle force development by exchanging native cardiac troponin (cTn) with different ratio mixtures of wild‐type (WT) cTn and cTn containing WT cardiac troponin T/I + cardiac troponin C (cTnC) D65A (a site II inactive cTnC mutant). Maximal Ca2+‐activated force (Fmax) increased in less than a linear manner with WT cTn. This contrasts with results we obtained previously in skeletal fibres (using sTnC D28A, D65A) where Fmax increased in a greater than linear manner with WT sTnC, and suggests that Ca2+ binding to each functional Tn activates < 7 actins of a structural regulatory unit in cardiac muscle and > 7 actins in skeletal muscle. The Ca2+ sensitivity of force and rate of force redevelopment (ktr) was leftward shifted by 0.1–0.2 −log [Ca2+] (pCa) units as WT cTn content was increased, but the slope of the force–pCa relation and maximal ktr were unaffected by loss of near‐neighbour RU interactions. Cross‐bridge inhibition (with butanedione monoxime) or augmentation (with 2 deoxy‐ATP) had no greater effect in cardiac muscle with disruption of near‐neighbour RU interactions, in contrast to skeletal muscle fibres where the effect was enhanced. The rate of Ca2+ dissociation was found to be > 2‐fold faster from whole cardiac Tn compared with skeletal Tn. Together the data suggest that in cardiac (as opposed to skeletal) muscle, Ca2+ binding to individual Tn complexes is insufficient to completely activate their corresponding RUs, making thin filament activation level more dependent on concomitant Ca2+ binding at neighbouring Tn sites and/or crossbridge feedback effects on Ca2+ binding affinity.
Dexamethasone induces the expression of metalloproteinase inhibitor TIMP‐1 in the murine cerebral vascular endothelial cell line cEND
Authors: Förster Carola , Kahles Timo , Kietz Silke , Drenckhahn Detlev
Published: February 2007

In many neuroinflammatory conditions, including multiple sclerosis (MS), encephalitis, meningitis, brain tumours and cerebral ischaemia, the matrix metalloproteinases (MMPs) play an important role in disrupting the blood–brain barrier (BBB). Normally under tight regulation, increased MMP‐9 cerebrospinal fluid levels and excessive proteolytic activity is detected in the blood and cerebrospinal fluid in patients with acute MS. MMP‐9 is a member of the type IV collagenases, which attack components of the endothelial basal lamina, including type IV collagen. The disruption of the BBB and clinical symptoms can be reduced with different inhibitors to MMPs including activators of tissue inhibitor of metalloproteinases‐1 (TIMP‐1), the cognate tissue inhibitor of MMP‐9. Since intravenous glucocorticoid (GC) treatment reduces the levels of MMP‐9 markedly in patients, we hypothesized that GC effects might be mediated by transcriptional activation of the TIMP‐1 gene in addition to reported repressive effects on MMP‐9 transcription. Our results provide direct evidence that GCs increase TIMP‐1 in the brain endothelial cell line cEND, prevent alterations in microvascular integrin α1 subunit expression and help maintain endothelial barrier function in response to pro‐inflammatory stimuli (TNFα administration). GC‐induced up‐regulation of TIMP‐1 expression by the CNS vascular endo‐thelium may thus play a role in preservation of the endothelial basal lamina and maintain integrin α1 and tight junction protein expression important for vessel wall integrity.
Objective Function Effect Based Pattern Search—Theoretical Framework Inspired by 3D Component Layout
Authors: Aladahalli Chandankumar , Cagan Jonathan , Shimada Kenji
Published: February 2007

Though pattern search algorithms have been successfully applied to three-dimensional (3D) component layout problems, a number of unanswered questions remain regarding their parameter tuning. One such question is the scheduling of patterns in the search. Current pattern search methods treat all patterns similarly and all of them are active from the beginning to the end of the search. Observations from 3D component layout motivate the question whether patterns should be introduced in some different order during the search. This paper presents a novel method for scheduling patterns that is inspired by observations from 3D component layout problems. The new method introduces patterns into the search in the decreasing order of a priori expectation of the objective function change due to the patterns. Pattern search algorithms based on the new pattern schedule run 30% faster on average than conventional pattern search based algorithms on 3D component layout problems and general 2D multimodal surface minimization problems. However since determining the expected change in objective function value due to the patterns is expensive, we explore approximations using domain information.
On Calculating the Degrees of Freedom or Mobility of Overconstrained Linkages: Single-Loop Exceptional Linkages
Authors: Rico J. M. , Ravani B.
Published: February 2007

This paper reformulates and extends the new, group theoretic, mobility criterion recently developed by the authors, (Rico, J. M., and Ravani, B., 2003, ASME J. Mech. Des., 125, pp. 70–80). In contrast to the Kutzbach-Grübler criterion, the new mobility criterion and the approach presented apply to a large class of single-loop overconstrained linkages. The criterion is reformulated, in terms of the well-known Jacobian matrices, for exceptional linkages and extended to linkages with partitioned mobility and trivial linkages. Several examples are included.
A Route to the Brightest Possible Neutron Source?
Authors: Taylor Andrew , Dunne Mike , Bennington Steve , Ansell Stuart , Gardner Ian , Norreys Peter , Broome Tim , Findlay David , Nelmes Richard
Published: February 2007

We review the potential to develop sources for neutron scattering science and propose that a merger with the rapidly developing field of inertial fusion energy could provide a major step-change in performance. In stark contrast to developments in synchrotron and laser science, the past 40 years have seen only a factor of 10 increase in neutron source brightness. With the advent of thermonuclear ignition in the laboratory, coupled to innovative approaches in how this may be achieved, we calculate that a neutron source three orders of magnitude more powerful than any existing facility can be envisaged on a 20- to 30-year time scale. Such a leap in source power would transform neutron scattering science.
Decagonal and Quasi-Crystalline Tilings in Medieval Islamic Architecture
Authors: Lu Peter J. , Steinhardt Paul J.
Published: February 2007

The conventional view holds that girih (geometric star-and-polygon, or strapwork) patterns in medieval Islamic architecture were conceived by their designers as a network of zigzagging lines, where the lines were drafted directly with a straightedge and a compass. We show that by 1200 C.E. a conceptual breakthrough occurred in which girih patterns were reconceived as tessellations of a special set of equilateral polygons (“girih tiles”) decorated with lines. These tiles enabled the creation of increasingly complex periodic girih patterns, and by the 15th century, the tessellation approach was combined with self-similar transformations to construct nearly perfect quasi-crystalline Penrose patterns, five centuries before their discovery in the West.
Shaping of Elastic Sheets by Prescription of Non-Euclidean Metrics
Authors: Klein Yael , Efrati Efi , Sharon Eran
Published: February 2007

The connection between a surface's metric and its Gaussian curvature (Gauss theorem) provides the base for a shaping principle of locally growing or shrinking elastic sheets. We constructed thin gel sheets that undergo laterally nonuniform shrinkage. This differential shrinkage prescribes non-Euclidean metrics on the sheets. To minimize their elastic energy, the free sheets form three-dimensional structures that follow the imposed metric. We show how both large-scale buckling and multiscale wrinkling structures appeared, depending on the nature of possible embeddings of the prescribed metrics. We further suggest guidelines for how to generate each type of feature.
Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication
Authors: Triboulet Robinson , Mari Bernard , Lin Yea-Lih , Chable-Bessia Christine , Bennasser Yamina , Lebrigand Kevin , Cardinaud Bruno , Maurin Thomas , Barbry Pascal , Baillat Vincent , Reynes Jacques , Corbeau Pierre , Jeang Kuan-Teh , Benkirane Monsef
Published: February 2007

MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1–infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.
Gene Body-Specific Methylation on the Active X Chromosome
Authors: Hellman Asaf , Chess Andrew
Published: February 2007

Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific methylation of the inactive X chromosome has been demonstrated at promoter CpG islands, but the overall pattern of methylation on the active X(Xa) and inactive X (Xi) chromosomes is unknown. We performed allele-specific analysis of more than 1000 informative loci along the human X chromosome. The Xa displays more than two times as much allele-specific methylation as Xi. This methylation is concentrated at gene bodies, affecting multiple neighboring CpGs. Before X inactivation, all of these Xa gene body–methylated sites are biallelically methylated. Thus, a bipartite methylation-demethylation program results in Xa-specific hypomethylation at gene promoters and hypermethylation at gene bodies. These results suggest a relationship between global methylation and expression potentiality.
Redefining the Age of Clovis: Implications for the Peopling of the Americas
Authors: Waters Michael R. , Stafford Thomas W.
Published: February 2007

The Clovis complex is considered to be the oldest unequivocal evidence of humans in the Americas, dating between 11,500 and 10,900 radiocarbon years before the present (
14
C yr B.P.). Adjusted
14
C dates and a reevaluation of the existing Clovis date record revise the Clovis time range to 11,050 to 10,800
14
C yr B.P. In as few as 200 calendar years, Clovis technology originated and spread throughout North America. The revised age range for Clovis overlaps non-Clovis sites in North and South America. This and other evidence imply that humans already lived in the Americas before Clovis.
Imaging of Single Organic Molecules in Motion
Authors: Koshino Masanori , Tanaka Takatsugu , Solin Niclas , Suenaga Kazutomo , Isobe Hiroyuki , Nakamura Eiichi
Published: February 2007

High-resolution transmission electron microscopy revealed nearly atomically precise images of stepping conformational change and translational motion of single hydrocarbon molecules confined in carbon nanotubes. One or two C12 or C22 alkyl chains were tethered to a carborane end group and then embedded in the nanotubes. Images of the hydrocarbon chains interacting with each other and with a graphitic surface provide information on three-dimensional structures and dynamic molecular interactions that cannot be obtained by other analytical methods.
A Slicer-Mediated Mechanism for Repeat-Associated siRNA 5' End Formation in
Drosophila
Authors: Gunawardane Lalith S. , Saito Kuniaki , Nishida Kazumichi M. , Miyoshi Keita , Kawamura Yoshinori , Nagami Tomoko , Siomi Haruhiko , Siomi Mikiko C.
Published: February 2007

In
Drosophila
, repeat-associated small interfering RNAs (rasiRNAs) are produced in the germ line by a Dicer-independent pathway and function through the PIWI subfamily of Argonautes to ensure silencing of retrotransposons. We sequenced small RNAs associated with the PIWI subfamily member AGO3. Although other members of PIWI, Aubergine (Aub) and Piwi, associated with rasiRNAs derived mainly from the antisense strand of retrotransposons, AGO3-associated rasiRNAs arose mainly from the sense strand. Aub- and Piwi-associated rasiRNAs showed a strong preference for uracil at their 5′ ends, and AGO3-associated rasiRNAs showed a strong preference for adenine at nucleotide 10. Comparisons between AGO3- and Aub-associated rasiRNAs revealed pairs of rasiRNAs showing complementarities in their first 10 nucleotides. Aub and AGO3 exhibited Slicer activity in vitro. These data support a model in which formation of a 5′ terminus within rasiRNA precursors is guided by rasiRNAs originating from transcripts of the other strand in concert with the Slicer activity of PIWI.
Role of α-actin in muscle damage of injured athletes in comparison with traditional markers
Authors: Martínez Amat Antonio , Marchal Corrales Juan Antonio , Rodríguez Serrano Fernando , Boulaiz Houria , Prados Salazar Jose Carlos , Hita Contreras Fidel , Caba Perez Octavio , Carrillo Delgado Esmeralda , Martín Ignacio , Aranega Jimenez Antonia
Published: February 2007

Objective:In order to identify a reliable marker for the early detection of muscle injuries in sports, α-actin protein and other markers of muscle damage were studied in sera of uninjured sportspeople and those with skeletal muscle injury.

Methods:Blood samples were obtained from 20 sportspeople with skeletal muscle injury and 48 uninjured sportspeople. Immunoassays were performed to determine cardiac troponin I (TnI), troponin T, lactate dehydrogenase and myoglobin concentrations. Western blot and densitometry were used to measure α-actin concentrations. Skeletal muscle damage was diagnosed according to physical examination, MRI findings and the biochemical criterion of a creatine kinase value >500 IU/l (Rosalki method, Beckman Instruments SL, Fullerton, California, USA). Results were also compared with previously obtained data on injured and uninjured non-sportspeople.

Results:The mean serum concentration of α-actin was significantly higher in sportspeople with muscle damage (10.49 μg/ml) than in uninjured sportspeople (3.99 μg/ml). Sera from injured sportspeople showed higher levels of α-actin than of troponin or myoglobin. No significant difference in TnI levels was observed between the groups.

Conclusions:According to these results, α-actin is a new and reliable marker of skeletal muscle damage in sportspeople which can be used for the detection of muscle injury. Possible cross interference between skeletal and cardiac muscle damage can be discriminated by the combined use of α-actin and TnI. These data suggest that early measurement of α-actin in sportspeople with suspected muscle damage will allow them to receive earlier and more effective treatment and to return sooner to the practice of their sport.
Use of permitted drugs in Italian professional soccer players
Authors: Taioli Emanuela
Published: February 2007

Objectives:To assess the frequency and quantity of usage of permitted drugs by Italian professional soccer players.

Methods:A cohort of 1041 professional soccer players from the two Italian major leagues was assembled during the season 2003–4; 743 of the 785 (94.6%) subjects available on the day of the interview answered an epidemiological questionnaire, which included questions on the type and frequency of use of several permitted drugs.

Results:92.6% of players reported having used oral anti-inflammatory products in the previous year, and most of them were current users (86.1%). 36% of the players, mostly current users, reported the use of analgesics. 82.8% of the players reported current use of supplements, and 28% reported using vitamins.

Conclusions:The regular use of several permitted drugs is very high among professional soccer players. The description of players’ behaviour is the first step towards regular monitoring of the players’ need for, and use of, vitamins, supplements and other permitted drugs.
ANALYTICAL DYNAMICS OF NEURON PULSE PROPAGATION
Authors: PHILLIPSON PAUL E. , SCHUSTER PETER
Published: February 2007

The four-dimensional Hodgkin–Huxley equations describe the propagation in space and time of the action potential v(z) along a neural axon with z = x + ct and c being the pulse speed. The potential v(z), which is parameterized by the temperature, is driven by three gating functions, m(z), n(z) and h(z), each of which obeys formal first order kinetics with rate constants that are represented as nonlinear functions of the potential v. It is shown that this system can be analytically simplified (i) in the number of gating functions and (ii) in the form of associated rate functions while retaining to close approximation quantitative fidelity to computer solutions of the exact equations over the complete temperature range for which stable pulses exist. At a given temperature we record two solutions (T < T max ) corresponding to a high-speed and a low-speed branch in speed-temperature plots, c(T), or no solution (T > T max ). The pulse is considered as composed of two contiguous parts: (i) a pulse front extending from v(0) = 0 to a pulse maximum v = V max , and (ii) a pulse back extending from V max through a pulse minimum V min to a final regression back to v(z → ∞) = 0. An approximate analytic solution is derived for the pulse front, which is predicted to propagate at a speed c(T) = 1203 Θ⅜ (T° C ) cm/sec, [Formula: see text] in close agreement with computer solution of the exact Hodgkin–Huxley equations for the entire pulse. These results provide the basis for a derivation of two-dimensional differential equation systems for the pulse front and pulse back, which predict the pulse maximum and minimum over the operational temperature range 0 ≤ T ≤ 25° C , in close agreement with the exact equations. Most neuron dynamics studies have been based on voltage clamp experiments featuring external current injection in place of self-generating pulse propagation. Since the behaviors of the gating functions are similar, it is suggested that the present approximations might be applicable to such situations as well as to the dynamics of myelinated fibers.
PATTERN FORMATION IN NOISY SELF-REPLICATING SPOTS
Authors: MUNTEANU ANDREEA , SOLÉ RICARD V.
Published: February 2007

Among reaction–diffusion systems showing Turing patterns, the diffusive Gray–Scott model [Pearson, 1993], stands out by showing self-replicating patterns (spots), which makes it the ideal simple model for developmental research. A first study of the influence of noise in the Gray–Scott model was performed by Lesmes et al. [2003] concluding that there exists an optimal noise intensity for which spot multiplication is maximal. Here we show in detail the transition from nonspotlike to spotlike pattern, with the identification of a wide range of noise intensities instead of an optimal value for which this transition occurs. Additional studies also reveal that noise produces a shift and a shrinkage of the regions of spatial patterns in the parameters space, without introducing qualitative changes to the diagram.
PHASE DIAGRAMS AND CORRELATION INEQUALITIES OF A THREE-STATE STOCHASTIC EPIDEMIC MODEL ON THE SQUARE LATTICE
Authors: OHTSUKA KAZUMICHI , KONNO NORIO , MASUDA NAOKI , AIHARA KAZUYUKI
Published: February 2007

We study a three-state stochastic particle system on the square lattice, which extends the contact process. The phase diagram is analyzed by the mean-field approximation, the pair approximation, and numerics. The pair approximation turns out to be better than the meanfield ansatz. We also show that the Harris-FKG type correlation inequalities approximately hold in the present model.
ON THE INFLUENCE OF THE RESONANT FREQUENCIES RATIO ON A STABLE PERIODIC SOLUTION OF TWO IMPACTING OSCILLATORS
Authors: CZOLCZYNSKI KRZYSZTOF , KAPITANIAK TOMASZ
Published: February 2007

A system that consists of two impacting oscillators with damping has been considered in this paper. The goal of the studies was to determine the relation between the values of resonant frequencies of the oscillators and the existence of their stable periodic motion. This paper indicates various origins of the periodicity of motion and offers a some advice to the designers of systems with impacts. Especially, the results of the considerations point out some potentially dangerous consequences of the improper value of the resonant frequencies ratio.
Inhibitory neuromuscular transmission mediated by the P2Y1purinergic receptor in guinea pig small intestine
Authors: Wang Guo-Du , Wang Xi-Yu , Hu Hong-Zhen , Liu Sumei , Gao Na , Fang Xiucai , Xia Yun , Wood Jackie D.
Published: February 2007

ATP is a putative inhibitory neurotransmitter responsible for inhibitory junction potentials (IJPs) at neuromuscular junctions (IJPs) in the intestine. This study tested the hypothesis that the purinergic P2Y1receptor subtype mediates the IJPs. IJPs were evoked by focal electrical stimulation in the myenteric plexus and recorded with “sharp” intracellular microelectrodes in the circular muscle coat. Stimulation evoked three categories of IJPs: 1) purely purinergic IJPs, 2) partially purinergic IJPs, and 3) nonpurinergic IJPs. Purely purinergic IJPs were suppressed by the selective P2Y1purinergic receptor antagonist MRS2179. Purely purinergic IJPs comprised 26% of the IJPs. Partially purinergic IJPs (72% of the IJPs) consisted of a component that was abolished by MRS2179 and a second unaffected component. The MRS2179-insensitive component was suppressed or abolished by inhibition of formation of nitric oxide by Nω-nitro-l-arginine methyl ester (l-NAME) in some, but not all, IJPs. An unidentified neurotransmitter, different from nitric oxide, mediated the second component in these cases. Nonpurinergic IJPs were a small third category (4%) of IJPs that were abolished by l-NAME and unaffected by MRS2179. Exogenous application of ATP evoked IJP-like hyperpolarizing responses, which were blocked by MRS2179. Application of apamin, which suppresses opening of small-conductance Ca2+-operated K+channels in the muscle, decreased the amplitude of the purinergic IJPs and the amplitude of IJP-like responses to ATP. The results support ATP as a neurotransmitter for IJPs in the intestine and are consistent with the hypothesis that the P2Y1purinergic receptor subtype mediates the action of ATP.
Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes
Authors: Dewland Thomas A. , Androne Ana Silvia , Lee Forrester A. , Lampert Rachel J. , Katz Stuart D.
Published: February 2007

Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies, but in some cases these indexes appear to yield discordant information. We utilized pyridostigmine, an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal, to further characterize parasympathetic regulation of rest and postexercise heart rate. We measured time- and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine (30 mg) and matching placebo in randomized, double-blind, crossover trial. In sedentary adults, pyridostigmine decreased resting heart rate [from 66.7 (SD 12.6) to 58.1 beats/min (SD 7.6), P = 0.005 vs. placebo] and increased postexercise heart rate recovery at 1 min [from 40.7 (SD 10.9) to 45.1 beats/min (SD 8.8), P = 0.02 vs. placebo]. In trained athletes, pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo. Time- and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort. The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation. The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway.
Na+-d-glucose cotransporter in the kidney of Leucoraja erinacea: molecular identification and intrarenal distribution
Authors: Althoff Thorsten , Hentschel Hartmut , Luig Jutta , Schütz Hendrike , Kasch Myriam , Kinne Rolf K.-H.
Published: February 2007

Studies on membrane vesicles from the kidney of Leucoraja erinacea suggested the sole presence of a sodium-d-glucose cotransporter type 1 involved in renal d-glucose reabsorption. For molecular characterization of this transport system, an mRNA library was screened with primers directed against conserved regions of human sglt1. A cDNA was cloned whose nucleotide and derived amino acid sequence revealed high homology to sodium glucose cotransporter 1 (SGLT1). Xenopus laevis oocytes injected with the respective cRNA showed sodium-dependent high-affinity uptake of d-glucose. Many positions considered functionally essential for sodium glucose cotransporter 1 (SGLT1) are also found in the skate protein. High conservation preferentially in transmembrane helices and small linking loops suggests early appearance and continued preservation of these regions. Larger loops, especially loop 13, which is associated with phlorizin binding, were more variable, as is the interaction with the specific inhibitor in various species. To study the intrarenal distribution of the transporter, a skate SGLT1-specific antibody was generated. In cryosections of skate kidney, various nephron segments could be differentiated by lectin staining. Immunoreaction with the antibody was observed in the proximal tubule segments PIa and PIIa, the early distal tubule, and the collecting tubule. Thus Leucoraja, in contrast to the mammalian kidney, employs only SGLT1 to reabsorb d-glucose in the early, as well as in the late segments of the proximal tubule and probably also in the late distal tubule (LDT). Thereby, it differs also partly from the kidney of the close relative Squalus acanthias, which uses SGLT2 in more distal proximal tubule segments but shows also expression in the later nephron parts.
Resistance exercise and cyclooxygenase (COX) expression in human skeletal muscle: implications for COX-inhibiting drugs and protein synthesis
Authors: Weinheimer E. M. , Jemiolo B. , Carroll C. C. , Harber M. P. , Haus J. M. , Burd N. A. , LeMoine J. K. , Trappe S. W. , Trappe T. A.
Published: February 2007

We have shown that ibuprofen and acetaminophen block cyclooxygenase (COX) synthesis of prostaglandin PGF2αand the muscle protein synthesis increase following resistance exercise. Confusingly, these two drugs are purported to work through different mechanisms, with acetaminophen apparently unable to block COX and ibuprofen able to nonspecifically block COX-1 and COX-2. A recently discovered intron-retaining COX, now known to have three variants, has been shown to be sensitive to both drugs. We measured the expression patterns and levels of the intron 1-retaining COX-1 variants (-1b1, -1b2, and -1b3), COX-1, and COX-2 at rest and following resistance exercise to help elucidate the COX through which PGF2α, ibuprofen, and acetaminophen regulate muscle protein synthesis. Skeletal muscle biopsy samples were taken from 16 individuals (8M, 8F) before, 4, and 24 h after a bout of resistance exercise and analyzed using real-time RT-PCR. Relatively few individuals expressed the intron 1-retaining COX-1b variants (COX-1b1, -1b2, and -1b3) at any time point, and when expressed, these variants were in very low abundance. COX-1 was the most abundant COX mRNA before exercise and remained unchanged ( P > 0.05) following exercise. COX-2 was not expressed before exercise, but increased significantly ( P < 0.05) at 4 and 24 h after exercise. The inconsistent and low levels of expression of the intron 1-retaining COX-1 variants suggest that these variants are not likely responsible for the inhibition of PGF2αproduction and skeletal muscle protein synthesis after resistance exercise by ibuprofen and acetaminophen. Skeletal muscle-specific inhibition of COX-1 or COX-2 by these drugs should be considered.
Venous hemodynamic responses to acute temperature increase in the rainbow trout (Oncorhynchus mykiss)
Authors: Sandblom Erik , Axelsson Michael
Published: February 2007

Many ectotherms regularly experience considerable short-term variations in environmental temperature, which affects their body temperature. Here we investigate the cardiovascular responses to a stepwise acute temperature increase from 10 to 13 and 16°C in rainbow trout ( Oncorhynchus mykiss). Cardiac output increased by 20 and 31% at 13 and 16°C, respectively. This increase was entirely mediated by an increased heart rate (fH), whereas stroke volume (SV) decreased significantly by 20% at 16°C. The mean circulatory filling pressure (MCFP), a measure of venous capacitance, increased with temperature. Central venous pressure (Pven) did not change, whereas the pressure gradient for venous return (MCFP-Pven) was significantly increased at both 13 and 16°C. Blood volume, as measured by the dilution of51Cr-labeled red blood cells, was temperature insensitive in both intact and splenectomized trout. This study demonstrates that venous capacitance in trout decreases, but cardiac filling pressure as estimated by Pvendoes not change when cardiac output increases during an acute temperature increase. SV was compromised as fHincreased with temperature. The decreased capacitance likely serves to prevent passive pooling of blood in the venous periphery and to maintain cardiac filling pressure and a favorable pressure gradient for venous return.
Angiotensin-converting enzyme inhibitor captopril attenuates ventilator-induced lung injury in rats
Authors: Jiang Jiunn-Song , Wang Leng-Fang , Chou Hsiu-Chu , Chen Chung-Ming
Published: February 2007

We hypothesized that lung inflammation and parenchymal apoptosis in ventilator-induced lung injury (VILI) are related to ANG II and assessed the ability of the angiotensin-converting enzyme inhibitor captopril to attenuate VILI in rats. Adult male Sprague-Dawley rats were randomized to receive two ventilation strategies for 2 h: 1) tidal volume of 40 ml/kg, respiratory rate of 25 breaths/min, and inspiratory O2fraction of 0.21 [high-volume, 0 positive end-expiratory pressure (HVZP) group] and 2) injection of captopril (100 mg/kg ip) 30 min before HVZP ventilation (HVZP + CAP group). Another group, which did not receive ventilation, served as the control. Mean arterial pressure was significantly lower in the HVZP + CAP group than in the HVZP group at 2 h of ventilation. Total protein levels were significantly higher in bronchoalveolar lavage fluid (BALF) recovered from HVZP-ventilated rats than from controls. BALF macrophage inflammatory protein-2 and lung ANG II were significantly higher in the HVZP group than in the control and HVZP + CAP groups. Lung ANG II levels correlated positively with BALF protein and macrophage inflammatory protein-2. The number of apoptotic airway and alveolar wall cells was significantly higher in the HVZP and HVZP + CAP groups than in the control group and significantly lower in the HVZP + CAP group than in the HVZP group. These results suggest that the efficiency of captopril to attenuate VILI is related to reduction of inflammatory cytokines and inhibition of apoptosis and indicate that VILI is partly mediated by the local angiotensin system.
Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations
Authors: Svenson Karen L. , Von Smith Randy , Magnani Phyllis A. , Suetin Heather R. , Paigen Beverly , Naggert Jürgen K. , Li Renhua , Churchill Gary A. , Peters Luanne L.
Published: February 2007

The breadth of genetic and phenotypic variation among inbred strains is often underappreciated because assessments include only a limited number of strains. Evaluation of a larger collection of inbred strains provides not only a greater understanding of this variation but collectively mimics much of the variation observed in human populations. We used a high-throughput phenotyping protocol to measure females and males of 43 inbred strains for body composition (weight, fat, lean tissue mass, and bone mineral density), plasma triglycerides, high-density lipoprotein and total cholesterol, glucose, insulin, and leptin levels while mice consumed a high-fat, high-cholesterol diet. Mice were fed a chow diet until they were 6–8 wk old and then fed the high-fat diet for an additional 18 wk. As expected, broad phenotypic diversity was observed among these strains. Significant variation between the sexes was also observed for most traits measured. Additionally, the response to the high-fat diet differed considerably among many strains. By the testing of such a large set of inbred strains for many traits, multiple phenotypes can be considered simultaneously and thereby aid in the selection of certain inbred strains as models for complex human diseases. These data are publicly available in the web-accessible Mouse Phenome Database ( http://www.jax.org/phenome ), an effort established to promote systematic characterization of biochemical and behavioral phenotypes of commonly used and genetically diverse inbred mouse strains. Data generated by this effort builds on the value of inbred mouse strains as a powerful tool for biomedical research.
X chromosome loss and ageing
Authors: Russell L.M. , Strike P. , Browne C.E. , Jacobs P.A.
Published: February 2007

The detection of a low level 45,X cell line during routine cytogenetic analysis in an adult female can be difficult to interpret. In the absence of recent information regarding loss of the X chromosome and ageing, we undertook a prospective study. A total of 19,650 cells from 655 females aged from birth to 80 years were screened cytogenetically. The frequency of X chromosome loss ranged from 0.07% at age <16 years to 7.3% at >65 years of age and showed a highly significant quadratic relationship between X chromosome loss and ageing (P ≤ 0.00001). We have produced a graphic representation that provides a minimum baseline age-related rate of X chromosome loss. This should assist diagnostic cytogenetics laboratories to determine the significance of 45,X cell lines detected in women of all ages. We also compared the frequency of 45,X cells in women referred with at least one spontaneous abortion with those referred for other reasons and found no significant difference. Thus, in our population, an excess of 45,X cells is not associated with pregnancy loss.
The optimization of sample treatment for spectral karyotyping with applications for human tumour cells
Authors: Loja T. , Kuglik P. , Oltova A. , Smuharova P. , Zitterbart K. , Bajciova V. , Veselska R
Published: February 2007

Spectral karyotyping (SKY) represents an important tool for the investigation of the complex chromosomal rearrangements (CCRs) in many human malignancies which may be difficult to characterize by conventional banding techniques. The main goal of our work was to optimize the most important steps in the preparation of molecular cytogenetic slides for a SKY protocol. This approach consisted of optimization of both the aging procedure and protease pretreatment of the slides, with special regard given to the preservation of chromosome structure and shape, as well as to the intensity of hybridization signals. The best results were obtained with a chemical aging procedure using SSC or ethanol in combination with trypsin pretreatment applied at a higher concentration for a shorter period of pretreatment. A resulting protocol for SKY also applicable to human solid tumour cells was subsequently proposed. The practical potential of the SKY technique was demonstrated on examples of two types of human embryonal tumours – neuroblastoma and Wilms’ tumour, in which some kinds of chromosomal aberrations were not detectable by means of classic cytogenetic methods.
Assignment of six genes to bovine chromosomes 5 and 16 by fluorescence in situ hybridization, radiation hybrid mapping and genetic linkage analysis
Authors: Hansen G.R. , Abbey C.A. , Gaile D.P. , Raudsepp T. , Chowdhary B.P. , Womack J.E. , Gill C.A.
Published: February 2007

Several quantitative trait loci for beef carcass traits have been mapped to bovine chromosome 5. The objective of this study was to map six candidate genes for these traits by fluoresence in situ hybridization, genetic linkage analysis and radiation hybrid mapping. MYF5 and MYF6 were assigned to 5q13, WIF1 to 5q23 and MMP19 to 5q25. A paralog of MYF5 (putatively MYOG) was assigned to 16q12. A novel microsatellite placed MYF5 and MYF6 10.4 cM from BM6026 and 19.1 cM from BL23 on the genetic linkage map. MYF5 (62.6 cR), WNT10B (319.5 cR), WIF1 (500.8 cR) and MMP19 (701.2 cR) were also integrated into the 5000Rad radiation hybrid map.
Identification of a new repetitive element in the sex chromosomes of Leporinus elongatus (Teleostei: Characiformes: Anostomidae): new insights into the sex chromosomes of Leporinus
Authors: Parise-Maltempi P.P. , Martins C. , Oliveira C. , Foresti F.
Published: February 2007

Leporinuselongatus represents an interesting model for studies on chromosome evolution since it possesses a conspicuous ZZ/ZW sex chromosome system that has been characterized mainly by basic cytogenetic techniques. In the present study we describe a dispersed repetitive element (named LeSpeI) related to the sex chromosomes of L.elongatus. Females revealed clusters of LeSpeI on the long arm of the W chromosome and in the acrocentric NOR-bearing chromosome pair. In males, the signal was restricted to the pericentromeric region of the NOR-bearing chromosomes. Considering the results obtained in the present study using FISH, NOR and C-banding, together with findings from previous studies, it can be inferred that the sex chromosome system of L. elongatus is still undergoing an evolutionary process. The data suggest novelties in relation to the sex chromosomes of the genus Leporinus with the description of a multiple sex chromosome system involving the NOR-bearing chromosomes. Therefore, it is hypothesized that the simple ZW chromosome system previously described for L. elongatus rather is a multiple Z1Z1Z2Z2/Z1W1Z2W2 system.