bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Requirement for Conserved Tryptophans in Human Immunodeficiency Virus Type 1 Vif for the Selective Suppression of APOBEC3G and APOBEC3F
Authors: Tian Chunjuan , Yu Xianghui , Zhang Wei , Wang Tao , Xu Rongzhen , Yu Xiao-Fang
Published: February 2006

APOBEC3G (A3G) and related cytidine deaminases, such as APOBEC3F (A3F), are potent inhibitors of retroviruses. Formation of infectious human immunodeficiency virus type 1 (HIV-1) requires suppression of multiple cytidine deaminases by Vif. Whether HIV-1 Vif recognizes various APOBEC3 proteins through a common mechanism is unclear. The domains in Vif that mediate APOBEC3 recognitions are also poorly defined. The N-terminal region of HIV-1 Vif is unusually rich in Trp residues, which are highly conserved. In the present study, we examined the role of these Trp residues in the suppression of APOBEC3 proteins by HIV-1 Vif. We found that most of the highly conserved Trp residues were required for efficient suppression of both A3G and A3F, but some of these residues were selectively required for the suppression of A3F but not A3G. Mutant Vif molecules in which Ala was substituted for Trp79 and, to a lesser extent, for Trp11 remained competent for A3G interaction and its suppression; however, they were defective for A3F interaction and therefore could not efficiently suppress the antiviral activity of A3F. Interestingly, while the HIV-1 Vif-mediated degradation of A3G was not affected by the different C-terminal tag peptides, that of A3F was significantly influenced by its C-terminal tags. These data indicate that the mechanisms by which HIV-1 Vif recognizes its target molecules, A3G and A3F, are not identical. The fact that several highly conserved residues in Vif are required for the suppression of A3F but not that of A3G suggests a critical role for A3F in the restriction of HIV-1 in vivo.
Molecular characterisation of pancreatic ductal adenocarcinoma in patients under 40
Authors: Bergmann F , Aulmann S , Wente M N , Penzel R , Esposito I , Kleeff J , Friess H , Schirmacher P
Published: February 2006

Background:Pancreatic ductal adenocarcinoma (PDAC) rarely affects people under 40.

Objectives:To determine whether the clinical, pathomorphological and genetic features of PDAC occurring in young patients (⩽40 years) differ from those in elderly patients.

Methods:Clinical and pathomorphological data were obtained from seven patients presenting with PDAC, with age ranging from 35 to 40 years of age (mean 38 years). All tumours were characterised by using immunohistochemistry and molecular genetics.

Results:All seven patients were women and lacked an association to cancer-predisposing genetic syndromes. Four patients were smokers and one had non-hereditary chronic pancreatitis. Pathomorphologically, tumours in three patients displayed moderate differentiation and four showed poor differentiation including one adenosquamous carcinoma. All tumours showed overexpression of transforming growth factor β1 and loss or significant reduction of Smad4. Accumulation of p53 and overexpression of epidermal growth factor receptor (EGFR) were seen in five and four patients, respectively. No expression of p16, oestrogen hormone receptor or progesterone receptor was found. Mismatch repair gene products (MutL homologue 1 (MLH1), MSH2 and MSH6) were expressed in all tumours. Mutational analyses showed K-rasmutations in only three of the seven tumours.

Conclusion:A large clinical, pathomorphological and genetic overlap of PDAC in young patients aged under 40 is seen with that in elderly patients. The existence of yet undefined initiating events of pancreatic carcinogenesis is suggested by the low rate of K-rasmutations, in at least a subgroup of young patients.
Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer
Authors: Parrella P , Mazzarelli P , Signori E , Perrone G , Marangi G F , Rabitti C , Delfino M , Prencipe M , Gallo A P , Rinaldi M , Fabbrocini G , Delfino S , Persichetti P , Fazio V M
Published: February 2006

Background:Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks.

Aim:To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas.

Methods:Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70–Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls.

Results:A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins.

Conclusions:Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.
Associations of perceived work strain with nicotine dependence in a community sample
Authors: John U , Riedel J , Rumpf H-J , Hapke U , Meyer C
Published: February 2006

Background:Little is known about work strain and smoking, and even less about work strain and nicotine dependence.

Aim:To investigate the relations of perceived work strain with nicotine dependence among an adult general population sample.

Method:Cross sectional survey with a probability sample of residents of a northern German area with 4075 participants, aged 18–64 years (participation rate 70.2%). The current study is based on 2549 participants who were working 15 or more hours per week. Face to face at-home computer aided interviews (World Health Organization Composite International Diagnostic Interview) were carried out. Work strain, defined as high work demand and low work control, was assessed with a questionnaire. Nicotine dependence was diagnosed according to the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association. In addition, the Fagerström Test for Nicotine Dependence (FTND) was used.

Results:Subjects with work strain had an odds ratio of 1.6 (95% CI 1.2 to 2.3) for nicotine dependence compared to those who had no work strain. In a general linear model, higher work strain was associated with a stronger relation between work demand and work control and the FTND. The findings were adjusted for alcohol use disorders, occupational status, age, and sex.

Conclusion:Perceived work strain is related to nicotine dependence in this general adult population.
Associations between temporary employment and occupational injury: what are the mechanisms?
Authors: Benavides F G , Benach J , Muntaner C , Delclos G L , Catot N , Amable M
Published: February 2006

Objective:To determine whether observed higher risks of occupational injury among temporary workers are due to exposure to hazardous working conditions and/or to lack of job experience level.

Methods:Data systematically recorded for 2000 and 2001 by the Spanish Ministry of Labour and Social Affairs on fatal and non-fatal traumatic occupational injuries were examined by type of employment and type of accident, while adjusting for gender, age, occupation, and length of employment in the company. In the study period there were 1500 fatal and 1 806 532 non-fatal traumatic occupational injuries that occurred at the workplace. Incidence rates and rate ratios (RR) were estimated using Poisson regression models.

Results:Temporary workers showed a rate ratio of 2.94 for non-fatal occupational injuries (95% CI 2.40 to 3.61) and 2.54 for fatal occupational injuries (95% CI 1.88 to 3.42). When these associations were adjusted by gender, age, occupation, and especially length of employment, they loose statistic significance: 1.05 (95% CI 0.97 to 1.12) for non-fatal and 1.07 (95% CI 0.91 to 1.26) for fatal.

Conclusions:Lower job experience and knowledge of workplace hazards, measured by length of employment, is a possible mechanism to explain the consistent association between temporary workers and occupational injury. The role of working conditions associated with temporary jobs should be assessed more specifically.
Mortality among Paris sewage workers
Authors: Wild P , Ambroise D , Benbrik E , Tiberguent A , Massin N
Published: February 2006

Objectives:To describe the mortality of Paris sewage workers.

Methods:A cohort of all Paris sewage workers since 1970 was established and followed up in mortality until 1999. The causes of death were determined by matching with a national database. The mortality rates were compared to the rates of a local reference population.

Results:A large excess in mortality (standardised mortality ratio (SMR) = 1.25; 530 cases, 95% CI 1.15 to 1.36) and in particular mortality from cancer (SMR = 1.37, 235 cases) was detected which was particularly important in the subgroup of subjects who had left employment because they resigned or were laid off (SMR = 1.77; 50 cases). The excess mortality is to a large extent due to alcohol related diseases (SMR = 1.65, 122 cases) especially malignant (SMR = 1.85, 16 cases) and non-malignant (SMR =  1.68, 38 cases) liver diseases, lung cancer (SMR = 1.47, 68 cases), and infectious diseases (SMR =  1.86, 25 cases). The SMRs for some diseases (all cancers, cancers of the oesophagus and lung, all alcohol related diseases) seem to increase with duration of employment as a sewage worker. Other than lung cancer, smoking related diseases were not in excess.

Conclusion:The increased mortality by both malignant and non-malignant liver diseases is probably due to excessive alcohol consumption, but could be partially the result of occupational exposure to chemical and infectious agents and interactions of these factors. The excess lung cancer is unlikely to be due to an increased smoking prevalence.
Applying a moving total mortality count to the cities in the NMMAPS database to estimate the mortality effects of particulate matter air pollution
Authors: Roberts S , Martin M A
Published: February 2006

Objectives:To apply a new method for estimating the association between daily ambient particulate matter air pollution (PM) and daily mortality to data from over 100 United States cities contained in the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) database and to see whether the results from the 90 cities NMMAPS analysis are robust to this different modelling approach. This new method has recently been shown to provide improved estimates for the association between PM and daily mortality when every-day PM data are unavailable. It avoids the need for selecting a lag of PM at which the mortality effects of PM are to be investigated.

Methods:With the aid of analytical methods and databases developed for NMMAPS, Poisson log linear models controlling for long term trends and weather effects were used to estimate the association between PM and mortality for cities in the NMMAPS database using the new method. A two stage Bayesian hierarchical model was then used to combine city specific estimates to form a national average PM mortality effect estimate.

Results:A 10 μg/m3increase in PM was associated with a 0.12% increment in total mortality and a 0.17% increment in cardiovascular and respiratory mortality. These results are consistent with those found in the NMMAPS analysis.

Conclusions:There is a statistically significant association between short term changes in PM and mortality on average for the cities contained in the NMMAPS database. These findings are further evidence that this widespread pollutant adversely affects public health.
THREE-DIMENSIONAL LATTICE BOLTZMANN MODEL RESULTS FOR COMPLEX FLUIDS ORDERING
Authors: AMATI G. , MASSAIOLI F. , GONNELLA G. , XU AIGUO , LAMURA A.
Published: February 2006

The kinetics of domain growth of fluid mixtures quenched from a disordered to a lamellar phase has been studied in three dimensions. We use a numerical approach based on the lattice Boltzmann method (LBM). A novel implementation for LBM which "fuses" the collision and streaming steps is used in order to reduce memory and bandwidth requirements. We find that extended defects between stacks of lamellae with different orientation dominate the late time dynamics.
MODELLING FORMATION AND EVOLUTION OF TRANSVERSE DUNE FIELDS
Authors: LEE JAE HWAN , SOUSA A. O. , PARTELI E. J. R. , HERRMANN H. J.
Published: February 2006

We model formation and evolution of transverse dune fields. In the model, only the cross section of the dune is simulated. The only physical variable of relevance is the dune height, from which the dune width and velocity are determined, as well as phenomenological rules for interaction between two dunes of different heights. We find that dune fields with no sand on the ground between dunes are unstable, i.e., small dunes leave the higher ones behind. We then introduce a saturation length to simulate transverse dunes on a sand bed and show that this leads to stable dune fields with regular spacing and dune heights. Finally, we show that our model can be used to simulate coastal dune fields if a constant sand influx is considered, where the dune height increases with the distance from the beach, reaching a constant value.
CROSSOVER PHENOMENON AND UNIVERSALITY: FROM RANDOM WALK TO DETERMINISTIC SAND-PILES THROUGH RANDOM SAND-PILES
Authors: SHAPOVAL A. B. , SHNIRMAN M. G.
Published: February 2006

The sand-pile models exhibit a great diversity of behavioral patterns. The average height as a function on time points out the variety of the sand-pile's criticality. We define the classes of universality for the sand-piles in terms of the spectrum of the average height. The definition, in particular, distinguishes two classes with Manna's and Bak et al. sand-piles as the typical representatives. The one-parametric family of the models investigated in this paper develops a crossover between the classes and introduces the infinite quantity of other sand-pile's classes. The parameter is the number of grains that any unstable cell transfers to its neighbors. The sand-piles admit a certain normalization generating unified laws. The spectral approach increases the precision of the universalities from our size distribution analysis. The latter describes the sand-piles' typical distribution, sets the correspondence between the sand-piles with small and large parameter values, but fails to determine their diversity.
3D GRAVITY AND NONLINEAR COSMOLOGY
Authors: DEVECCHI F. P. , FROEHLICH M. L.
Published: February 2006

By the inclusion of an additional term, nonlinear in the scalar curvature R, it is tested if dark energy could rise as a geometrical effect in 3D gravitational formulations. We investigate a cosmological fluid obeying a non-polytropic equation of state (the van der Waals equation) that is used to construct the energy–momentum tensor of the sources, representing the hypothetical inflaton in gravitational interaction with a matter contribution. Following the evolution in time of the scale factor, its acceleration, and the energy densities of constituents it is possible to construct the description of an inflationary 3D universe, followed by a matter-dominated era. For later times it is verified that, under certain conditions, the nonlinear term in R can generate the old 3D universe in accelerated expansion, where the ordinary matter is represented by the barotropic limit of the van der Waals constituent.
EXACT ROLLING TACHYON IN NONCOMMUTATIVE FIELD THEORY
Authors: KIM YOONBAI , KWON O-KAB
Published: February 2006

We find exact rolling tachyon solutions in DBI type noncommutative field theory with constant open string metric and noncommutative parameter on an unstable D p-brane. Their functional shapes span all possible homogeneous rolling tachyon solutions, i.e. they are hyperbolic-cosine, hyperbolic-sine, and exponential under 1/cosh runaway NC tachyon potential. Even if general DBI type NC electric field is turned on, only constant electric field satisfies equations of motion and again exact homogeneous rolling tachyon solutions are obtained.
SPACETIME CURVATURE COUPLING OF SPINORS IN EARLY UNIVERSE: NEUTRINO ASYMMETRY AND A POSSIBLE SOURCE OF BARYOGENESIS
Authors: DEBNATH UJJAL , MUKHOPADHYAY BANIBRATA , DADHICH NARESH
Published: February 2006

It is well known that when a fermion propagates in curved spacetime, its spin couples to the curvature of background spacetime. We propose that this interaction for neutrinos propagating in early curved universe could give rise to a new set of dispersion relations and then neutrino asymmetry at equilibrium. We demonstrate this with the Bianchi models which describe the homogeneous but anisotropic and axially symmetric universe. If the lepton number violating processes freeze out at 10-37 s when temperature T~1015 GeV , neutrino asymmetry of the order of 10-10 can be generated. A net baryon asymmetry of the same magnitude can thus be generated from this lepton asymmetry either by a GUT B-L symmetry or by the electroweak sphaleron processes which have B+L symmetry.
BRIGHT SOLITONS MANAGED BY FESHBACH RESONANCE IN BOSE–EINSTEIN CONDENSATES
Authors: LIANG Z. X. , ZHANG Z. D. , LIU W. M.
Published: February 2006

We review the recent experimental and theoretical advances in the generation of matter wave solitons in Bose–Einstein condensates. In particular, the controlled generation and dynamics of stable bright solitons by mean of Feshbach resonance techniques is discussed in details. Several aspects are taking into account, including the variation of the scattering length due to Feshbach resonance, the safe parameters against the collapse and the experimental implications of our scenario.
DISCRETE LAPLACE–BELTRAMI OPERATOR ON SPHERE AND OPTIMAL SPHERICAL TRIANGULATIONS
Authors: XU GUOLIANG
Published: February 2006

In this paper we first modify a widely used discrete Laplace-Beltrami operator proposed by Meyer et al over triangular surfaces, and then we show that the modified discrete operator has some convergence properties over the triangulated spheres. A sequence of spherical triangulations which is optimal in certain sense and leads to smaller truncation error of the discrete Laplace-Beltrami operator is constructed. Optimal hierarchical spherical triangulations are also given. Truncation error bounds of the discrete Laplace-Beltrami operator over the constructed triangulations are provided.
NUMERICAL SIMULATIONS OF SYNCHRONIZED PACING
Authors: PUWAL STEFFAN , ROTH BRADLEY J.
Published: February 2006

Pak et al.1 demonstrated an experimental technique for termination of fibrillation in the heart. Their method used feedback pacing, and resulted in an eight-fold increase in the success rate compared to conventional overdrive pacing. Our goal is to study this technique numerically. Computer simulations were performed using the Fenton-Karma model of membrane excitability, with a correction introduced to allow more realistic modeling of external stimulation. We found that both overdrive pacing and independent synchronized pacing resulted in significantly improved success compared to spontaneous termination of fibrillation. We conclude that synchronized pacing may provide a low-energy alternative to traditional defibrillation.
ANTI-TUMOR IMMUNITY AND TUMOR ANTI-IMMUNITY IN A MATHEMATICAL MODEL OF TUMOR IMMUNOTHERAPY
Authors: FORYŚ URSZULA , WANIEWSKI JACEK , ZHIVKOV PETAR
Published: February 2006

A two-dimensional system of ordinary differential equations is used to characterize the basic types of phase portraits of the immune system — tumor interactions model, and to study the impact of anti-immune activity by tumor on the outcome of immunotherapy. The focus is on specific (acquired) immunity and different forms of immunotherapy as active therapy with in vivo stimulation of the immunity and passive one with infusion of ex vivo produced specific immunity. The analysis is performed for two families of stimulation function, which describes the dynamics of the stimulation of the immune system by tumor antigens: (1) antigen dependent and (2) antigen per one immunity unit dependent functions, with Michaelis-Menten and sigmoid functions in each family. We show that there are no limit cycles in the system and that anti-immune activity by tumor changes all equilibrium points from global to local ones. In the latter case, the immune system has no control over the growth of large tumors. Furthermore, if the immunity is weak, the immune system cannot eradicate even small tumors. The weak immunity and stimulation strength result in unrestricted tumor growth. The patterns of asymptotic behavior of the system do not depend on the type of the stimulation function, but do depend on its parameters. Our results reflect the basic clinical and experimental knowledge about immunotherapy and its effectiveness and yield new suggestions for an efficient immunotherapy.
IMPULSIVE SELECTIVE HARVESTING IN A LOGISTIC FISHERY MODEL WITH TIME DELAY
Authors: PEI YONGZHEN , CHEN LANSUN , LI CHANGGUO , WANG CHUNHUA
Published: February 2006

In this work, we consider a logistic fishery model and discuss the selective impulsive harvesting of fish above a certain age or size by incorporating a time delay in the impulsive harvesting term. It is proved that there exists an asymptotically stable positive periodic solution [Formula: see text] when the catchability coefficient h is less than some critical value [Formula: see text]. It is concluded that [Formula: see text] and [Formula: see text] are increasing with respect to l. Simulations shows that the delayed harvesting is advantageous to the sustainability of the population.
HIGH-ORDER ACCURATE NUMERICAL SCHEMES FOR THE PARABOLIC EQUATION
Authors: FLOURI EVANGELIA T. , EKATERINARIS JOHN A. , KAMPANIS NIKOLAOS A.
Published: February 2006

Efficient, high-order accurate methods for the numerical solution of the standard (narrow-angle) parabolic equation for underwater sound propagation are developed. Explicit and implicit numerical schemes, which are second- or higher-order accurate in time-like marching and fourth-order accurate in the space-like direction are presented. The explicit schemes have severe stability limitations and some of the proposed high-order accurate implicit methods were found conditionally stable. The efficiency and accuracy of various numerical methods are evaluated for Cartesian-type meshes. The standard parabolic equation is transformed to body fitted curvilinear coordinates. An unconditionally stable, implicit finite-difference scheme is used for numerical solutions in complex domains with deformed meshes. Simple boundary conditions are used and the accuracy of the numerical solutions is evaluated by comparing with an exact solution. Numerical solutions in complex domains obtained with a finite element method show excellent agreement with results obtained with the proposed finite difference methods.
WHAT IS WRONG WITH EIA AND SEA ANYWAY? A SCEPTIC'S PERSPECTIVE ON SUSTAINABILITY ASSESSMENT
Authors: MORRISON-SAUNDERS ANGUS , FISCHER THOMAS B
Published: February 2006

Environmental impact assessment (EIA) was initially introduced as an advocacy instrument for the biophysical environment in project decision-making. Strategic environmental assessment (SEA) evolved with a similar mission for strategic level proposals. However, recent trends towards more integration, particularly in the context of sustainability assessment (SA) mean that social and economic aspects are now frequently considered on a par with the environment in impact assessment processes. There are indications that this development will ultimately favour trade-offs towards socio-economic benefits, causing adverse environmental impacts. In this paper, we discuss problems connected with these types of integrated assessments. Based on observations of SA processes are actually environmentally unsustainable, we argue that the need for environment focussed EIA and true SEA in planning processes is now greater than ever. We suggest that until power relationships develop in a way that will allow integration in an environmentally sustainable manner, practitioners should not give up the benefits that have arisen from 35 years of EIA practice. We conclude that in our current world, there is nothing wrong with environmental advocacy — let's continue to use EIA and SEA effectively to protect the environment!
CONSUMER BEHAVIOR ANALYSIS BY GRAPH MINING TECHNIQUE
Authors: YADA KATSUTOSHI , MOTODA HIROSHI , WASHIO TAKASHI , MIYAWAKI ASUKA
Published: February 2006

In this paper, we discuss how graph mining system is applied to sales transaction data so as to understand consumer behavior. First, existing research of consumer behavior analysis for sequential purchase pattern is reviewed. Then we propose to represent the complicated customer purchase behavior by a directed graph retaining temporal information in a purchase sequence and apply a graph mining technique to analyze the frequent occurring patterns. In this paper, we demonstrate through the case of healthy cooking oil analysis how graph mining technology helps us understand complex purchase behavior.
THE FUNCTION OF HARMONY AND TRUST IN COLLABORATIVE CHANCE DISCOVERY
Authors: OEHLMANN RUEDIGER
Published: February 2006

Collaborative Chance Discovery aims at determining a rare event as a chance for future decision making from a set of potential chances that have been identified by computational methods. Typically based on these potential chances, the members of a workgroup will imagine scenarios that describe situations and event sequences during which a chance could be used. This paper describes a study of how scenarios may emerge from group interactions. Verbal protocols of two software design groups, who conducted the same design task, were analyzed. The experimental group additionally had to use social diagrams to externalize their changing views about the other group members. It was predicted that the externalization causes an increase of references to harmony and trust and that this increased awareness leads to improved scenarios. The protocol analysis confirmed this hypothesis and revealed details of the process of scenario emergence. The new insights gave rise to the proposal of a new model of scenario emergence based on externalizing social context, harmony and trust.
Role of reduced folate carrier in intestinal folate uptake
Authors: Balamurugan Krishnaswamy , Said Hamid M.
Published: February 2006

Studies from our laboratory and others have characterized different aspects of the intestinal folate uptake process and have shown that the reduced folate carrier (RFC) is expressed in the gut and plays a role in the uptake process. Little, however, is known about the actual contribution of the RFC system toward total folate uptake by the enterocytes. Addressing this issue in RFC knockout mice is not possible due to the embryonic lethality of the model. In this study, we describe the use of the new approach of lentivirus-mediated short hairpin RNA (shRNA) to selectively silence the endogenous RFC of the rat-derived intestinal epithelial cells (IEC-6), an established in vitro model for folate uptake, and examined the effect of such silencing on folate uptake. First we confirmed that the initial rate of [3H]folic acid uptake by IEC-6 cells was pH dependent with a markedly higher uptake at acidic compared with alkaline pH. We also showed that the addition of unlabeled folic acid to the incubation buffer leads to a severe inhibition (∼95%) in [3H]folic acid (16 nM) uptake at buffer pH 5.5 but not at buffer pH 7.4. We then examined the effect of treating (for 72 h) IEC-6 cells with RFC-specific shRNA on the levels of RFC protein and mRNA and observed substantial reduction in the levels of both parameters (∼80 and 78%, respectively). Such a treatment was also found to lead to a severe inhibition (∼90%) in initial rate of folate uptake at buffer pH 5.5 (but not at pH 7.4); uptake of the unrelated vitamin, biotin, on the other hand, was not affected by such a treatment. These results demonstrate that the RFC system is the major (if not the only) folate uptake system that is functional in intestinal epithelial cells.
TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons
Authors: Kang Dawon , Kim Donghee
Published: February 2006

Dorsal root ganglion (DRG) neurons express mRNAs for many two-pore domain K+ (K2P) channels that behave as background K+ channels. To identify functional background K+ channels in DRG neurons, we examined the properties of single-channel openings from cell-attached and inside-out patches from the cell bodies of DRG neurons. We found seven types of K+ channels, with single-channel conductance ranging from 14 to 120 pS in 150 mM KCl bath solution. Four of these K+ channels showed biophysical and pharmacological properties similar to TRESK (14 pS), TREK-1 (112 pS), TREK-2 (50 pS), and TRAAK (73 pS), which are members of the K2P channel family. The molecular identity of the three other K+ channels could not be determined, as they showed low channel activity and were observed infrequently. Of the four K2P channels, the TRESK-like (14 pS) K+ channel was most active at 24°C. At 37°C, the 50-pS (TREK-2 like) channel was the most active and contributed the most (69%) to the resting K+ current, followed by the TRESK-like 14-pS (16%), TREK-1-like 112-pS (12%), and TRAAK-like 73-pS (3%) channels. In DRG neurons, mRNAs of all four K2P channels, as well as those of TASK-1 and TASK-3, were expressed, as judged by RT-PCR analysis. Our results show that TREKs and TRESK together contribute >95% of the background K+ conductance of DRG neurons at 37°C. As TREKs and TRESK are targets of modulation by receptor agonists, they are likely to play an active role in the regulation of excitability in DRG neurons.
Reciprocal activation of HSF1 and HSF3 in brain and blood tissues: is redundancy developmentally related?
Authors: Shabtay Ariel , Arad Zeev
Published: February 2006

Transcriptional induction of heat-shock genes in response to temperature elevation and other stresses is mediated by heat-shock transcription factors (HSFs). Avian cells express two redundant heat-shock responsive factors, HSF1 and HSF3, which differ in their activation kinetics and threshold induction temperature. Unlike the ubiquitous activation of HSF1, the DNA-binding activity of HSF3 is restricted to undifferentiated avian cells and embryonic tissues. Herein, we report a reciprocal activation of HSF1 and HSF3 in vivo. Whereas HSF1 mediates transcriptional activity only in the brain upon severe heat shock, HSF3 is exclusively activated in blood cells upon light, moderate, and severe heat shock, promoting induction of heat-shock genes. Although not activated, HSF1 is expressed in blood cell nuclei in a granular appearance, suggesting regulation of genes other than heat-shock genes. Intraspecific comparison of heat-sensitive and heat-resistant fowl strains indicates that the unique activation pattern of HSF3 in blood tissue is a general phenomenon, not related to thermal history. Taken together, HSF1 and HSF3 mediate transcriptional activity of adult tissues and differentiated cells in a nonredundant manner. Instead, an exclusive, tissue-specific activation is observed, implying that redundancy may be developmentally related. The physiological and developmental implications are discussed.
Intravenous 6-hydroxydopamine attenuates vasopressin and oxytocin secretion stimulated by hemorrhage and hypotension but not hyperosmolality in rats
Authors: Stocker Sean D. , Wilson Melinda E. , Madden Christopher J. , Lone Usman , Sved Alan F.
Published: February 2006

The present study sought to determine whether chemical destruction of peripheral catecholaminergic fibers with 6-hydroxydopamine (6OHDA) attenuates vasopressin (VP) and oxytocin (OT) secretion stimulated by hemorrhage, hypotension, and hyperosmolality. Rats received 6OHDA (100 mg/kg iv) or vehicle (1 ml/kg iv) on days 1 and 7, and experiments were performed on day 8. Serial hemorrhage (4 samples of 2 ml per 300 g body wt at 10-min intervals) increased plasma VP and OT levels in both groups; however, the increase in plasma VP and OT levels was significantly attenuated in 6OHDA-treated vs. control rats despite a significantly lower mean arterial blood pressure. Similarly, the increase in plasma VP and OT levels in response to hypotension produced by the selective arteriolar vasodilator diazoxide was significantly attenuated in 6OHDA-treated rats. In marked contrast to hemorrhage and hypotension, hyperosmolality produced by an infusion of 1 M NaCl (2 ml/h iv) stimulated increases in plasma VP and OT levels that were not different between 6OHDA-treated and control rats. In a parallel set of experiments, intravenous 6OHDA treatment reduced dopamine-β-hydroxylase immunoreactivity in the posterior pituitary but had no substantial effect in the hypothalamic paraventricular and supraoptic nuclei. In each experiment, the pressor response to tyramine (250 μg/kg iv) was significantly attenuated in 6OHDA-treated rats, thereby confirming that 6OHDA treatment destroyed sympathetic catecholaminergic fibers. Collectively, these findings suggest that catecholaminergic fibers located outside the blood-brain barrier contribute to VP and OT secretion during hemorrhage and arterial hypotension.
Distribution of myonuclei and microtubules in live muscle fibers of young, middle-aged, and old mice
Authors: Bruusgaard J. C. , Liestøl K. , Gundersen K.
Published: February 2006

We have recently published a new technique for visualizing nuclei in living muscle fibers of intact animals, based on microinjection of labeled DNA into single myofibers, excluding satellite cells (Bruusgaard JC, Liestol K, Ekmark M, Kollstad K, and Gundersen K. J Physiol 551: 467–478, 2003). In the present study, we use this technique to study fiber segments of soleus and extensor digitorum longus (EDL) muscles from mice aged 2, 14, and 23 mo. As the animals maturing from 2 to 14 mo, they displayed an increase in size and number of nuclei. Soleus showed little change in nuclear domain size, whereas this increased by 88% in the EDL. For 14-mo-old animals, no significant correlation between fiber size and nuclear number was observed ( R2 = 0.18, P = 0.51) despite a fourfold variation in cytoplasmic volume. This suggests that size and nuclear number is uncoupled in middle-aged mice. When animals aged from 14 to 23 mo, EDL IIb, but not soleus, fibers atrophied by 41%. Both EDL and soleus displayed a reduction in number of nuclei: 20 and 16%, respectively. A positive correlation between number of nuclei and size was observed at 2 mo, and this reappeared in old mice. The atrophy in IIb fibers at old age was accompanied by a disturbance in the orderly positioning of nuclei that is so prominent in glycolytic fibers at younger age. In old animals, changes in nuclear shape and in the peri- and internuclear microtubule network were also observed. Thus changes in myonuclear number and distribution, perhaps related to alterations in the microtubular network, may underlie some of the adverse consequences of aging on skeletal muscle size and function.
CO2/H+ chemoreceptors in the cerebellar fastigial nucleus do not uniformly affect breathing of awake goats
Authors: Martino P. F. , Hodges M. R. , Davis S. , Opansky C. , Pan L. G. , Krause K. , Qian B. , Forster H. V.
Published: February 2006

Our objective in this study was to test the hypothesis that focal acidosis (FA) in the cerebellar fastigial nucleus (CFN) of awake goats arising from global brain acidosis induced by increasing inspired CO2 will increase breathing. FA was created by reverse microdialysis of mock cerebral spinal fluid, equilibrated with 6.4, 25, 50, or 80% CO2 through chronically implanted microtubules (cannula). Dialysis with 6.4% CO2 had no significant effects on any physiological parameters. However, microdialysis at higher levels of CO2 increased pulmonary ventilation (V̇i) in one group of studies and decreased V̇i in a second group and the difference between the groups was significant ( t = 9.16, P < 0.001). In one group of studies ( n = 8), FA with 50 and 80% CO2 significantly increased ( P < 0.05) V̇i by 16 and 12%, respectively, and significantly increased ( P < 0.05) heart rate by 13 and 9%, respectively. In contrast, in another group of studies ( n = 6), FA with 25 and 50% CO2 significantly decreased ( P < 0.05) V̇i by 7 and 10%, respectively. In this group oxygen consumption was decreased during dialysis with 80% CO2. On the basis of histology, we estimate that the increased and decreased responses were associated with FA primarily in the rCFN and cCFN, respectively. We conclude that there are CO2/H+-sensitive neurons in the CFN that do not uniformly affect breathing. In addition, the significant changes in heart rate and oxygen consumption during FA indicate that the CFN can also influence non-respiratory-related control systems.
Resonance in the human medial gastrocnemius muscle during cyclic ankle bending exercise
Authors: Takeshita Daisuke , Shibayama Akira , Muraoka Tetsuro , Muramatsu Tadashi , Nagano Akinori , Fukunaga Tetsuo , Fukashiro Senshi
Published: February 2006

We investigated the behavior of the muscle tendon unit (MTU) of the medial gastrocnemius muscle during cyclic ankle bending exercise at eight different frequencies (ranging from 1.33 to 3.67 Hz). The changes in the length of fascicle in the muscle during the exercises were determined by real-time ultrasound imaging. The coordinates of anatomical references and the ground reaction force were determined from video recording and a force plate, respectively. The length change of the MTU (the distance from the origin to insertion of the muscle) was calculated from changes in the knee and ankle joint angles. It was found that the amplitude ratio and phase difference between the fascicle and MTU lengths were both dependent on the movement frequency. At lower frequencies, the fascicle lengths varied almost in phase with the MTU length, whereas they varied out of phase at the higher frequencies. At intermediate frequency, the amplitude of the fascicle became very small compared with that of the MTU, which is considered resonance. We constructed a mechanical model of the MTU based on a notion of forced oscillation in a mass-spring system. The obtained data were well explained by the model. It was concluded that the behavior of the MTU highly depends on the movement frequency due to the viscoelasticity of the MTU.
Does fitness level modulate the cardiovascular hemodynamic response to exercise?
Authors: Stickland Michael K. , Welsh Robert C. , Petersen Stewart R. , Tyberg John V. , Anderson William D. , Jones Richard L. , Taylor Dylan A. , Bouffard Marcel , Haykowsky Mark J.
Published: February 2006

Subjects with greater aerobic fitness demonstrate better diastolic compliance at rest, but whether fitness modulates exercise cardiac compliance and cardiac filling pressures remains to be determined. On the basis of maximal oxygen consumption (V̇o2max), healthy male subjects were categorized into either low (LO: V̇o2max = 43 ± 6 ml·kg−1·min−1; n = 3) or high (HI: V̇o2max = 60 ± 3 ml·kg−1·min−1; n = 5) aerobic power. Subjects performed incremental cycle exercise to 90% V̇o2max. Right atrial (RAP) and pulmonary artery wedge (PAWP) pressures were measured, and left ventricular (LV) transmural filling pressure (TMFP = PAWP − RAP) was calculated. Cardiac output (CO) and stroke volume (SV) were determined by direct Fick, and LV end-diastolic volume (EDV) was estimated from echocardiographic fractional area change and Fick SV. There were no between-group differences for any measure at rest. At a submaximal workload of 150 W, PAWP and TMFP were higher ( P < 0.05) in LO compared with HI (12 vs. 8 mmHg, and 9 vs. 4 mmHg, respectively). At peak exercise, CO, SV, and EDV were lower in LO ( P < 0.05). RAP was not different at peak exercise, but PAWP (23 vs. 15 mmHg) and TMFP (12 vs. 6 mmHg) were higher in LO ( P < 0.05). Compared with less fit subjects, subjects with greater aerobic fitness demonstrated lower LV filling pressures during exercise, whereas SV and EDV were either similar (submaximal exercise) or higher (peak exercise), suggesting superior diastolic function and compliance.
Estrogen status and skeletal muscle recovery from disuse atrophy
Authors: McClung J. M. , Davis J. M. , Wilson M. A. , Goldsmith E. C. , Carson J. A.
Published: February 2006

Although estrogen loss can alter skeletal muscle recovery from disuse, the specific components of muscle regrowth that are estrogen sensitive have not been described. The primary purpose of this study was to determine the components of skeletal muscle mass recovery that are biological targets of estrogen. Intact, ovariectomized (OVX), and ovariectomized with 17β-estradiol replacement (OVX+E2) female rats were subjected to hindlimb suspension for 10 days and then returned to normal cage ambulation for the duration of recovery. Soleus muscle mass returned to control levels by day 7 of recovery in the intact animals, whereas OVX soleus mass did not recover until day 14. Intact rats recovered soleus mean myofiber cross-sectional area (CSA) by day 14 of recovery, whereas the OVX soleus remained decreased (42%) at day 14. OVX mean fiber CSA did return to control levels by day 28 of recovery. The OVX+E2 treatment group recovered mean CSA at day 14, as in the intact animals. Myofibers demonstrating central nuclei were increased at day 14 in the OVX group, but not in intact or OVX+E2 animals. The percent noncontractile tissue was also increased 29% in OVX muscle at day 14, but not in either intact or OVX+E2 groups. In addition, collagen 1a mRNA was increased 45% in OVX muscle at day 14 of recovery. These results suggest that myofiber growth, myofiber regeneration, and extracellular matrix remodeling are estrogen-sensitive components of soleus muscle mass recovery from disuse atrophy.
Central Pattern Generating Neurons Simultaneously Express Fast and Slow Rhythmic Activities in the Stomatogastric Ganglion
Authors: Bucher Dirk , Taylor Adam L. , Marder Eve
Published: February 2006

Neuronal firing patterns can contain different temporal information. It has long been known that the fast pyloric and the slower gastric motor patterns in the stomatogastric ganglion of decapod crustaceans interact. However, the bidirectional influences between the pyloric rhythm and the gastric mill rhythm have not been quantified in detail from preparations that spontaneously express both patterns in vitro. We found regular and stable spontaneous gastric and pyloric activity in 71% of preparations of the isolated stomatogastric nervous system of the lobster, Homarus americanus. The gastric [cycle period: 10.96 ± 2.67 (SD) s] and pyloric (cycle period: 1.35 ± 0.18 s) patterns showed bidirectional interactions and coordination. Gastric neuron firing showed preferred phases within the reference frame of the pyloric cycle. The relative timing and burst parameters of the pyloric neurons systematically changed within the reference frame of the gastric cycle. The gastric rhythm showed a tendency to run at cycle periods that were integer multiples of the pyloric periods, but coupling and coordination between the two rhythms were variable. We used power spectra to quantify the gastric and pyloric contributions to the firing pattern of each individual neuron. This provided us with a way to analyze the firing pattern of each gastric and pyloric neuron type individually without reference to either gastric or pyloric phase. Possible functional consequences of these network interactions for motor output are discussed.
Endogenous Activation of Supraoptic Nucleus κ-Opioid Receptors Terminates Spontaneous Phasic Bursts in Rat Magnocellular Neurosecretory Cells
Authors: Brown Colin H. , Leng Gareth , Ludwig Mike , Bourque Charles W.
Published: February 2006

Phasic activity in magnocellular neurosecretory vasopressin cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials (spikes) are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials (DAPs). Burst termination is believed to result from autocrine feedback inhibition of plateau potentials by the κ-opioid peptide, dynorphin, which is copackaged in vasopressin neurosecretory vesicles and exocytosed from vasopressin cell dendrites during phasic bursts. Here we tested this hypothesis, using intracellular recording in vitro to show that κ-opioid receptor antagonist administration enhanced plateau potential amplitude to increase postspike excitability during spontaneous phasic activity. The antagonist also increased postburst DAP amplitude in vitro, indicating that endogenous dynorphin probably reduces plateau potential amplitude by inhibiting the DAP mechanism. However, the κ-opioid receptor antagonist did not affect the slow depolarization that follows burst termination, suggesting that recovery from endogenous κ-opioid inhibition does not contribute to the slow depolarization. We also show, by extracellular single-unit recording, that that there is a strong random element in the timing of burst initiation and termination in vivo. Administration of a κ-opioid receptor antagonist eliminated the random element of burst termination but did not alter the timing of burst initiation. We conclude that dendritic dynorphin release terminates phasic bursts by reducing the amplitude of plateau potentials to reduce the probability of spike firing as bursts progress. By contrast, dendritic dynorphin release does not greatly influence the membrane potential between bursts and evidently does not influence the timing of burst initiation.
Sleep-Related Neural Activity in a Premotor and a Basal-Ganglia Pathway of the Songbird
Authors: Hahnloser Richard H. R. , Kozhevnikov Alexay A. , Fee Michale S.
Published: February 2006

During singing, neurons in premotor nucleus RA (robust nucleus of the arcopallium) of the zebra finch produce complex temporal sequences of bursts that are recapitulated during sleep. RA receives input from nucleus HVC via the premotor pathway, and also from the lateral magnocellular nucleus of the anterior nidopallium (LMAN), part of a basal ganglia-related circuit essential for vocal learning. We explore the propagation of sleep-related spike patterns in these two pathways and their influences on RA activity. We promote sleep in head-fixed birds by injections of melatonin and make single-neuron recordings from the three major classes of neurons in HVC: RA-projecting neurons, Area X-projecting neurons, and interneurons. We also record LMAN neurons that project to RA. In paired recordings, spike trains from identified HVC neuron types are strongly coherent with spike trains in RA neurons, whereas LMAN projection neurons on average exhibit only a weak coherency with neurons in HVC and RA. We further examine the relative roles of HVC and LMAN in generating RA burst sequences with reversible inactivation. Lidocaine inactivation of HVC completely abolishes bursting in RA, whereas inactivation of LMAN has no effect on burst rates in RA. In combination, our data suggest that in adult birds, RA burst sequences in sleep are driven via the premotor pathway from HVC. We present a simple generative model of spike trains in HVC, RA, and LMAN neurons that is able to qualitatively reproduce observed coherency functions. We propose that commonly observed coherency peaks at positive and negative time lags are caused by sequentially correlated HVC activity.