bluuebunny/crossref_metadata_2025 huggingface dataset:
α2- to β3-Adrenoceptor switch in 3T3-L1 preadipocytes and adipocytes: modulation by testosterone, 17β-estradiol, and progesterone
Authors: Monjo Marta , Pujol Esperanza , Roca Pilar
Published: February 2005

Sex steroid hormones are important factors in the determination of fat distribution and accumulation. The aim of this study was to investigate the effect of testosterone (T), 17β-estradiol (17βE), and progesterone (P) on adrenergic receptor (AR) gene expression in 3T3-L1 preadipocytes and adipocytes and their relation to the proliferation and differentiation processes. Our data clearly show that α2A-AR was the highest AR subtype expressed in preadipocytes, whereas in mature adipocytes was by far β3-AR. In the differentiation process to adipocytes, α2A-AR expression was decreased to 0.3-fold ( P < 0.01), whereas β3-AR was upregulated 578-fold ( P < 0.001) compared with preadipocytes. In addition, the expression of α2A-AR in preadipocytes was increased upon incubation with T, 17βE, and P, and a stimulation of proliferation was also observed in 17βE- and P-treated cells. In mature adipocytes, 17βE and P enhanced both α2A- and β3-AR gene expression (although the effects on β3-AR mRNA levels could be more relevant, since β3-AR was the most highly expressed), whereas T only increased α2A-AR mRNA levels. Leptin and adipocyte fatty acid-binding protein mRNA levels were higher after 17βE and P treatment, possibly indicating a proadipogenic effect of these hormones. In conclusion, this study indicates that AR gene expression is affected by these hormones in both preadipocytes and adipocytes, which could have potential importance when considering the role of ARs in the mechanisms underlying the sex-related differences in adipose tissue regional distribution.
Simulated first-phase insulin release using Humulin or insulin analog HIM2 is associated with prolonged improvement in postprandial glycemia
Authors: DiCostanzo Catherine A. , Moore Mary Courtney , Lautz Margaret , Scott Melanie , Farmer Ben , Everett Carrie A. , Still J. Gordon , Higgins Alan , Cherrington Alan D.
Published: February 2005

We examined the extent to which priming the liver with a pulse of Humulin or the insulin analog hexyl-insulin monoconjugate 2 (HIM2) reduces postprandial hyperglycemia. Somatostatin (0.5 μg·kg−1·min−1) was given with basal intraportal insulin and glucagon for 4.5 h into three groups of 42-h-fasted conscious dogs. From 0–5 min, group 1 (BI, n = 6) received saline, group 2 (HI, n = 6) received a Humulin pulse (10 mU·kg−1·min−1), and group 3 (HIM2, n = 6) received a HIM2 pulse (10 mU·kg−1·min−1). Duodenal glucose was infused (5.0 mg·kg−1·min−1) from 15 to 270 min. Arterial insulin in BI remained basal (6 ± 1 μU/ml) and peaked at 52 ± 15 (HI) and 164 ± 44 μU/ml (HIM2) and returned to baseline by 30 and 60 min, respectively. Arterial plasma glucose plateaued at 265 ± 20, 214 ± 15, and 193 ± 14 mg/dl in BI, HI, and HIM2. Glucose absorption was similar in all groups. Significant net hepatic glucose uptake occurred at 85, 55, and 25 min in BI, HI, and HIM2, respectively. Nonhepatic glucose clearance at 270 min differed among groups (BI, HI, HIM2): 0.62 ± 0.11, 0.76 ± 0.26, and 1.61 ± 0.29 ml·kg−1·min−1( P < 0.05). A brief (5-min) insulin pulse improved postprandial glycemia, stimulating hepatic glucose uptake and prolonging enhancement of nonhepatic glucose clearance. HIM2 was more effective than Humulin, perhaps because its lowered clearance caused higher levels at the liver and periphery and its biological activity was not reduced proportionally to its decreased clearance.
Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells
Authors: Zsiros Veronika , Hestrin Shaul
Published: February 2005

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.
Stationary solutions for integer‐valued autoregressive processes
Authors: Aly Emad-Eldin A. A. , Bouzar Nadjib
Published: February 2005

The purpose of this paper is to introduce and develop a family of
ℤ+‐valued autoregressive processes of order p (INAR(p)) by
using the generalized multiplication ⊙F of van Harn and
Steutel (1982). We obtain various distributional and regression
properties for these models. A number of stationary INAR(p) processes with specific marginals are presented and are shown to
generalize several existing models.
Mixed‐type duality for multiobjective fractional variational control problems
Authors: Patel Raman
Published: February 2005

The concept of mixed‐type duality has been extended to the class of
multiobjective fractional variational control problems. A number
of duality relations are proved to relate the efficient solutions
of the primal and its mixed‐type dual problems. The results are
obtained for ρ‐convex (generalized ρ‐convex) functions.
The results generalize a number of duality results previously
obtained for finite‐dimensional nonlinear programming problems
under various convexity assumptions.
Integral properties of certain classes of analytic functions withnegative coefficients
Authors: SăLăgean G. S.
Published: February 2005

We study integral properties of two classes of functions with
negative coefficients defined using differential operators. The
obtained results are sharp and they improve known results.
On the concepts of balls in a D‐metric space
Authors: Naidu S. V. R. , Rao K. P. R. , Rao N. Srinivasa
Published: February 2005

The various concepts of open balls in D‐metric spaces are studied in the case of certain D‐metric spaces and many results in the literature on such balls
are shown to be false.
Some multiple Gaussian hypergeometric generalizations ofBuschman‐Srivastava theorem
Authors: Qureshi M. I. , Khan M. Sadiq , Pathan M. A.
Published: February 2005

Some generalizations of Bailey′s theorem involving the product of
two Kummer functions 1F1 are obtained by using Watson′s
theorem and Srivastava′s identities. Its special cases yield
various new transformations and reduction formulae involving
Pathan′s quadruple hypergeometric functions
, Srivastava′s triple and quadruple hypergeometric
functions F(3), F(4), Lauricella′s quadruple
hypergeometric function , Exton′s multiple
hypergeometric functions ,
K10,
K13,
X8,
,
, Erdélyi′s multiple hypergeometric function
Hn,k, Khan and Pathan′s
triple hypergeometric function , Kampé de Fériet′s double hypergeometric function
, Appell′s double hypergeometric function of the second kind
F2, and the Srivastava‐Daoust function
.
Some known results of Buschman, Srivastava, and
Bailey are obtained.
Further remarks on systems of interlocking exact sequences
Authors: Hilton Peter , Joanna Su C.
Published: February 2005

In a system of interlocking sequences, the assumption that three
out of the four sequences are exact does not guarantee the
exactness of the fourth. In 1967, Hilton proved that,
with the additional condition that it is differential at the
crossing points, the fourth sequence is also exact. In this paper,
we trace such a diagram and analyze the relation between the
kernels and the images, in the case that the fourth sequence is
not necessarily exact. Regarding the exactness of the fourth
sequence, we remark that the exactness of the other three
sequences does guarantee the exactness of the fourth at
noncrossing points. As to a crossing point p, we need
the extra criterion that the fourth sequence is differential. One notices that the condition, for the
fourth sequence, that kernel ⊇ image at
p turns out to be equivalent to the “opposite” condition kernel
⊆ image. Next, for the kernel and the image at p of the fourth sequence,
even though they may not coincide, they are not far
different—they always have the same cardinality as sets, and
become isomorphic after taking quotients by a subgroup which is
common to both. We demonstrate these phenomena with an example.
Fully fuzzy prime semigroups
Authors: Shabir M.
Published: February 2005

We characterize those semigroups for which each
fuzzy ideal is prime. We also characterize those semigroups for
which each fuzzy right ideal is prime.
Compactness in intuitionistic fuzzy topological spaces
Authors: Ramadan A. A. , Abbas S. E. , Abd El-Latif A. A.
Published: February 2005

We introduce fuzzy almost continuous mapping, fuzzy weakly
continuous mapping, fuzzy compactness, fuzzy almost compactness,
and fuzzy near compactness in intuitionistic fuzzy topological
space in view of the definition of Šostak, and study some of
their properties. Also, we investigate the behavior of fuzzy
compactness under several types of fuzzy continuous mappings.
Corrected Fourier series and its application to function approximation
Authors: Zhang Qing-Hua , Chen Shuiming , Qu Yuanyuan
Published: February 2005

Any quasismooth function f(x) in a finite interval [0, x0], which has only a finite number of finite discontinuities and has only a finite number of extremes, can be approximated by a uniformly convergent Fourier series and a correction function. The correction function consists of algebraic polynomials and Heaviside step functions and is required by the aperiodicity at the endpoints (i.e., f(0) ≠ f(x0)) and the finite discontinuities in between. The uniformly convergent Fourier series and the correction function are collectively referred to as the corrected Fourier series. We prove that in order for the mth derivative of the Fourier series to be uniformly convergent, the order of the polynomial need not exceed (m + 1). In other words, including the no‐more‐than‐(m + 1) polynomial has eliminated the Gibbs phenomenon of the Fourier series until its mth derivative. The corrected Fourier series is then applied to function approximation; the procedures to determine the coefficients of the corrected Fourier series are illustrated in detail using examples.
Stabilization of nonlinear discrete‐time systems via a digital communication channel
Authors: Phat V. N. , Jiang J.
Published: February 2005

We deal with the stabilization problem for a class
of nonlinear discrete‐time systems via a digital
communication channel. We consider the case when the control
input is to be transmitted via communication channels with a
bit‐rate constraint. Under an appropriate growth condition
on the nonlinear perturbation, we establish sufficient
conditions for the global and local stabilizability of
semilinear and nonlinear discrete‐time systems,
respectively. A constructive method to design a feedback
stabilizing controller is proposed.
Optimality criteria for deterministic discrete‐time infinite horizon optimization
Authors: Schochetman Irwin E. , Smith Robert L.
Published: February 2005

We consider the problem of selecting an optimality criterion, when total costs diverge, in deterministic infinite horizon optimization over discrete time. Our formulation allows for both discrete and continuous state and action spaces, as well as time‐varying, that is, nonstationary, data. The task is to choose a criterion that is neither too overselective, so that no policy is optimal, nor too underselective, so that most policies are optimal. We contrast and compare the following optimality criteria: strong, overtaking, weakly overtaking, efficient, and average. However, our focus is on the optimality criterion of efficiency. (A solution is efficient if it is optimal to each of the states through which it passes.) Under mild regularity conditions, we show that efficient solutions always exist and thus are not overselective. As to underselectivity, we provide weak state reachability conditions which assure that every efficient solution is also average optimal, thus providing a sufficient condition for average optima to exist. Our main result concerns the case where the discounted per‐period costs converge to zero, while the discounted total costs diverge to infinity. Under the assumption that we can reach from any feasible state any feasible sequence of states in bounded time, we show that every efficient solution is also overtaking, thus providing a sufficient condition for overtaking optima to exist.
Elliptic GW invariants of blowups along curves and surfaces
Authors: Hu Jianxun , Zhang Hou-Yang
Published: February 2005

We established a relation between elliptic Gromov‐Witten invariants of a symplectic manifold M and its blowups along smooth curves and surfaces.
Image sets of folding surfaces
Authors: Breda Ana M. d′Azevedo
Published: February 2005

Isometric foldings are a special class of length‐preserving maps
of Riemannian manifolds and were initially studied by S.
Robertson. For an explanation of their topological and
combinatorial properties, see the related works of Ana Breda,
Altino Santos, M. El‐Ghoul, and E. M. Elkholy. Here, we explore
some properties of the singular set and describe the image set of
planar, spherical, and hyperbolic foldings.
Thermoelastic wave propagation in a rotating elastic mediumwithout energy dissipation
Authors: Roychoudhuri S. K. , Bandyopadhyay Nupur
Published: February 2005

A study is made of the propagation of time‐harmonic plane
thermoelastic waves of assigned frequency in an infinite
rotating medium using Green‐Naghdi model (1993) of linear
thermoelasticity without energy dissipation. A more general
dispersion equation is derived to examine the effect of
rotation on the phase velocity of the modified coupled
thermal dilatational shear waves. It is observed that in
thermoelasticity theory of type II (Green‐Naghdi model), the
modified coupled dilatational thermal waves propagate
unattenuated in contrast to the classical thermoelasticity
theory, where the thermoelastic waves undergo attenuation
(Parkus, Chadwick, and Sneddon). The solutions of the more
general dispersion equation are obtained for small
thermoelastic coupling by perturbation technique. Cases of
high and low frequencies are also analyzed. The rotation of
the medium affects both quasielastic dilatational and shear
wave speeds to the first order in ω
for low frequency, while the quasithermal wave speed is affected by rotation up
to the second power in ω. However, for large frequency,
rotation influences both the quasidilatational and shear wave
speeds to first order in ω and the quasithermal wave
speed to the second order in 1/ω.
Locating real eigenvalues of a spectral problem in fluid‐solid type structures
Authors: Voss Heinrich
Published: February 2005

Exploiting minmax characterizations for nonlinear and nonoverdamped eigenvalue problems, we prove the existence of a countable set of eigenvalues converging to ∞ and inclusion theorems for a rational spectral problem governing mechanical vibrations of a tube bundle immersed in an incompressible viscous fluid. The paper demonstrates that the variational characterization of eigenvalues is a powerful tool for studying nonoverdamped eigenproblems, and that the appropriate enumeration of the eigenvalues is of predominant importance, whereas the natural ordering of the eigenvalues may yield false conclusions.
Alexander of Aphrodisias on Universals: Two Problematic Texts
Authors:   Sharples
Published: February 2005

Two texts that raise problems for Alexander of Aphrodisias' theory of universals are examined. De anima 90.2-8 appears to suggest that universals are dependent on thought for their existence; this raises questions about the status both of universals and of forms. It is suggested that the passage is best interpreted as indicating that universals are dependent on thought only for their being recognised as universals. The last sentence of Quaestio 1.11 seems to assert that if the universal did not exist no individual would exist, thereby contradicting Alexander's position elsewhere. This seems to be a slip resulting from the fact that species with only one member are the exception rather than the rule.
Cartilage Restoration, Part 2: Techniques, Outcomes, and Future Directions
Authors: Alford J. Winslow , Cole Brian J.
Published: February 2005

In part 1 of this 2-part Current Concepts article, the authors reviewed the basic science of normal articular and meniscal cartilage and its response to injury. They reviewed the historical perspectives and basic science behind these various methods and presented a rationale for patient evaluation, treatment selection, and timing. In part 2, the authors review the specific indications for the treatment of chondral injuries and describe the techniques and outcomes of the various treatment options, including palliative, reparative, and restorative procedures. In addition, they will examine specific complex clinical scenarios emphasizing treatment options of comorbid conditions including ligament instability, meniscal deficiency, and malalignment. A limited review of the application of these techniques in joints other than the knee will also be presented. A conceptual algorithm is developed to assist in clinical decision making.
On Being Jewish
Authors: Sinclair Jennifer , Milner David
Published: February 2005

This article presents a qualitative study of Jewish identity in emerging adults between ages 18 and 27, drawn from across the mainstream British Jewish community. Eighteen in-depth interviews were conducted using interpretative phenomenological analysis. The interviews covered three main areas, focusing on the participants’ developmental history and current experience of being Jewish in Britain today: (a) early influences on Jewish identity, (b) the impact of attending university on Jewish identity, and (c) friendships, relationships and marriage. Interpretative phenomenological analysis yielded two superordinate themes of social identity and religious identity. These contained further important subthemes, of which three are highlighted here: kinship and connection, awareness of difference, and faith and observance. The pattern and importance of these shared dimensions of identity were unique to each individual. The findings may enhance our understanding of how it feels to be different as an emerging adult member of an ethnic or religious minority group.
Psychosocial and Cultural Factors Influencing Expectations of Menarche
Authors: Yeung Dannii Y. L. , Tang Catherine So-kum , Lee Antoinette
Published: February 2005

This study explored how psychosocial and cultural factors influenced expectations of menarche among 476 Chinese premenarcheal teenage girls. Results showed that participants’ expectations of menarche were largely negative and heavily influenced by cultural beliefs about menstruation. Findings of hierarchical regression analyses revealed that positive emotional expectations of menarche were best predicted by perceptions of menstruation as a natural event, possession of positive self-concept, and rejection of indigenous negative menstrual attitudes. Negative emotional expectations of menarche were best predicted by perceptions of menstruation as a negative event, by inadequate preparation for menarche, by endorsement of indigenous negative menstrual attitudes, and by older age.
Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate
Authors: Howard O. M. Zack , Dong Hui Fang , Su Shao Bo , Caspi Rachel R. , Chen Xin , Plotz Paul , Oppenheim Joost J.
Published: February 2005

We tested the hypothesis that interaction between autoantigens and chemoattractant receptors may be an important step in the development of autoimmunity. The retinal autoantigens S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP) can induce autoimmune uveitis in rodent models. We evaluated the chemotactic activity of S-Ag and IRBP and found that both induced migration of human and mouse immature dendritic cells (iDCs) and lymphocytes, but not neutrophils, monocytes, or mature DCs. Cross-desensitization studies and single-receptor transfected cells revealed that subfamily of alpha chemokine receptors CXCR5 and CXCR3 mediated the chemotactic effect of IRBP, while only CXCR3 was required for the chemotactic response to S-Ag. Examination of the relationships between chemoattraction and the ability to elicit pathology at the protein or peptide levels in the mouse uveitis model revealed dissociation of the capacity to induce uveitis, lymphocyte proliferation, and chemoattraction. These studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5.
Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244)
Authors: Eissmann Philipp , Beauchamp Lisa , Wooters Joe , Tilton John C. , Long Eric O. , Watzl Carsten
Published: February 2005

Triggering of 2B4 (CD244) can induce natural killer (NK)-cell activation, costimulation, or even inhibition of NK-cell activity. Here, we investigate the molecular basis for the different signals generated by 2B4. We show that the first immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of 2B4 is sufficient for 2B4-mediated NK-cell activation, whereas the third ITSM can negatively influence 2B4 signaling. We further identify signaling molecules that associate with 2B4. Signaling lymphocyte activation molecule-associated protein (SAP) can bind to all 4 ITSMs of 2B4 in a phosphorylation-dependent manner. The phosphorylated third ITSM can additionally recruit the phosphatases SHP-1, SHP-2, SHIP, and the inhibitory kinase Csk. SAP acts as an inhibitor of interactions between 2B4 and these negative regulatory molecules, explaining how 2B4 inhibits NK-cell activation in the absence of functional SAP, as occurs in cells from patients with X-linked lymphoproliferative syndrome (XLP). Recently, another function for SAP was proposed: SAP can recruit the kinase Fyn to the SLAM (CD150) immune receptor. We now show that Fyn can also associate with phosphorylated 2B4. Finally, we demonstrate that Fyn and Csk can both phosphorylate 2B4, suggesting a possible mechanism of 2B4 phosphorylation. (Blood. 2005;105:4722-4729)
Automated generation of heuristics for biological sequence comparison
Authors: Slater Guy St C , Birney Ewan
Published: February 2005

Background

Exhaustive methods of sequence alignment are accurate but slow, whereas heuristic approaches run quickly, but their complexity makes them more difficult to implement. We introduce bounded sparse dynamic programming (BSDP) to allow rapid approximation to exhaustive alignment. This is used within a framework whereby the alignment algorithms are described in terms of their underlying model, to allow automated development of efficient heuristic implementations which may be applied to a general set of sequence comparison problems.

Results

The speed and accuracy of this approach compares favourably with existing methods. Examples of its use in the context of genome annotation are given.

Conclusions

This system allows rapid implementation of heuristics approximating to many complex alignment models, and has been incorporated into the freely available sequence alignment program, exonerate.
Leisure-time versus full-day energy expenditure: a cross-sectional study of sedentarism in a Portuguese urban population
Authors: Gal Diane L , Santos Ana-Cristina , Barros Henrique
Published: February 2005

Background

Low physical activity is known to be a potential risk factor for cardiovascular disease. With high prevalence of cardiovascular diseases in the Portuguese urban population, little is known about how sedentary this population is and what factors are associated to sedentary lifestyles. This study's objective was to examine sedentary lifestyles and their determinants through a cross-sectional study.

Methods

2134 adults (18 years and older) were interviewed using a standard questionnaire, comprising of social, behavioural and clinical information. Time spent in a variety of activities per day, including: work, household chores, sports, sedentary leisure time and sleep, were self-reported. Energy expenditure was estimated based on the related metabolic equivalent (MET) and time spent in each activity (min/day). Those with less than 10% of energy expenditure at a moderate intensity of 4 METs or higher were categorised as sedentary. The proportion of sedentary people and 95% Confidence Intervals (CI) were calculated, and the magnitude of associations, between sedentary lifestyles and the population characteristics, were computed as age-adjusted odds ratios using logistic regression.

Results

Sedentarism in both genders during leisure time is high at 84%, however in full day energy expenditure, which includes physical activity at work, sleeping hours and household chores, 79% of males and 86% of females are found to be sedentary. In leisure-time only, increased age is associated with higher odds of being sedentary in both genders, as well as in women with increased BMI. In comparison, in full-day energy expenditure, sedentarism is more likely to occur in those with higher levels of education and in white-collar workers.

Conclusions

A high prevalence of sedentarism is found in the study participants when measuring leisure-time and full-day energy expenditure. The Portuguese population may therefore benefit from additional promotion of physical activity.
Low density DNA microarray for detection of most frequent TP53 missense point mutations
Authors: Rangel-López Angélica , Maldonado-Rodríguez Rogelio , Salcedo-Vargas Mauricio , Espinosa-Lara Juana Mercedes , Méndez-Tenorio Alfonso , Beattie Kenneth L
Published: February 2005

Background

We have developed an oligonucleotide microarray (genosensor) utilizing a double tandem hybridization technique to search for 9 point mutations located in the most frequently altered codons of the TP53 gene. Isolated and multiplexed PCR products, 108 and 92 bp long, from exons 7 and 8, respectively, were obtained from 24 different samples. Single-stranded target DNA was then prepared from isolated or multiplexed PCR products, through cyclic DNA synthesis. Independent ssDNA's were annealed with the corresponding pairs of labeled stacking oligonucleotides to create partially duplex DNA having a 7-nt gap, which contains the sequence that will be interrogated by the capture probes forming double tandem hybridization. In the case of multiplexed ssPCR products, only two stacking oligonucleotides were added per target, therefore the gap for the PCR products having two consecutive codons to be interrogated in exon 7 was 12 nt long, so only single tandem hybridization was produced with these respective probes.

Results

18 codon substitutions were found by DNA sequencing. In 13 of them a perfect correlation with the pattern of hybridization was seen (In 5 no signal was seen with the wt probe while a new signal was seen with the appropriate mutant probe, and in 8 more, as expected, no signal was seen with any probe due to the absence of the corresponding probe in the array). In 3 other cases a mutation was falsely suggested by the combination of the absence of the wild type signal along with a false signal in the other probe. In the other 2 cases the presence of the mutation was not detected due to the production of a false hybridization signal with the wild type probe. In both cases (false mutation or no mutation detected) relatively stable mismatched target/probe duplexes should be formed. These problems could be avoided by the addition of probes to improve the performance of the array.

Conclusion

Our results demonstrate that a simple TP53 microarray employing short (7-mer) probes, used in combination with single or double tandem hybridization approach and a simple or multiplex target preparation method, can identify common TP53 missense mutations from a variety of DNA sources with good specificity.
Initiation to heroin injecting among heroin users in Sydney, Australia: cross sectional survey
Authors: Day Carolyn A , Ross Joanne , Dietze Paul , Dolan Kate
Published: February 2005

Background

Heroin injection is associated with health and social problems including hepatitis C virus (HCV) transmission. Few studies have examined the circumstances surrounding initiation to heroin injecting, especially current users initiating others. The current study aimed to examine the age of first heroin use and injection; administration route of first heroin use; relationship to initiator; the initiation of others among a group of heroin users; and to examine these factors in relation to HCV status and risk.

Method

Heroin users in Sydney were recruited through needle and syringe programs, a methadone clinic and snowballing. Participants were interviewed about their own initiation to heroin use, blood-borne virus risk and knowledge, and whether they had initiated others to heroin injecting. Information on HCV status was collected via self-report. Data was analysed using univariate and multivariate statistical techniques for Normally distributed continuous and categorical data.

Results

The study recruited 399 heroin users, with a mean age of 31 years, 63% were male, 77% reported heroin as their primary drug and 59% were HCV positive (self-report). Mean age at first heroin use and injection was 19 and 21 years, respectively. The majority of heroin users commenced heroin use via injecting (65%), younger users (<25 years, 25–30 years) were less likely than older users (>30 years) to commence heroin use parenterally. Participants were initiated to injection mainly by friends (63%). Thirty-seven percent reported initiating others to heroin injection, but few factors were related to this behaviour. Those with longer heroin using careers were more likely to report initiating others to heroin injection, but were no more likely to have done so in the preceding 12 months. Participants who had initiated others were more likely to have shared injecting equipment (12 vs 23%), but were no more likely to be HCV positive (self-report) than those who did not.

Conclusion

Interventions to prevent heroin users initiating others to injecting are necessary. Peer groups may be well positioned to implement such interventions.
Spontaneous rupture of giant gastric stromal tumor into gastric lumen
Authors: Mehta Rajiv M , Sudheer Vayoth O , John Anil K , Nandakumar Raghavan R , Dhar Puneet S , Sudhindran Surendran , Balakrishnan Vallath
Published: February 2005

Background

Gastrointestinal stromal tumors (GIST) constitute a large majority of mesenchymal tumors of the gastrointestinal (GI) tract, which express the c-kit proto-oncogene protein, a cell membrane receptor with tyrosine kinase activity. GI stromal tumors of the stomach are usually associated with bleeding, abdominal pain or a palpable mass.

Case presentation

A 75-year-old male presented with upper abdominal pain and palpable mass. Computed tomographic (CT) scan of the abdomen showed a large mass arising in the posterior aspect of fundus, body, and greater curvature of the stomach. Second day after the admission, there was significant reduction in the size of the tumor, clinically as well as radiologically. Endoscopic biopsy showed large bulge in fundus and corpus of the stomach posteriorly with an opening in the posterior part of the corpus, and biopsy from the edge of the opening reveled GIST. Patient underwent curative resection.

Conclusion

Spontaneous ruptured of giant gastric stromal tumor is very rare presentation of stomach GIST. Thorough clinical examination and timely investigation can diagnose rare complication.
Kaposi's sarcoma associated herpes virus-encoded viral FLICE inhibitory protein activates transcription from HIV-1 Long Terminal Repeat via the classical NF-κB pathway and functionally cooperates with Tat
Authors: Sun Qinmiao , Matta Hittu , Chaudhary Preet M
Published: February 2005

Background

The nuclear transcription factor NF-κB binds to the HIV-1 long terminal repeat (LTR) and is a key regulator of HIV-1 gene expression in cells latently infected with this virus. In this report, we have analyzed the ability of Kaposi's sarcoma associate herpes virus (KSHV, also known as Human Herpes virus 8)-encoded viral FLIP (Fas-associated death domain-like IL-1 beta-converting enzyme inhibitory protein) K13 to activate the HIV-1 LTR.

Results

We present evidence that vFLIP K13 activates HIV-1 LTR via the activation of the classical NF-κB pathway involving c-Rel, p65 and p50 subunits. K13-induced HIV-1 LTR transcriptional activation requires the cooperative interaction of all three components of the IKK complex and can be effectively blocked by inhibitors of the classical NF-κB pathway. K13 mutants that lacked the ability to activate the NF-κB pathway also failed to activate the HIV-1 LTR. K13 could effectively activate a HIV-1 LTR reporter construct lacking the Tat binding site but failed to activate a construct lacking the NF-κB binding sites. However, coexpression of HIV-1 Tat with K13 led to synergistic activation of HIV-1 LTR. Finally, K13 differentially activated HIV-1 LTRs derived from different strains of HIV-1, which correlated with their responsiveness to NF-κB pathway.

Conclusions

Our results suggest that concomitant infection with KSHV/HHV8 may stimulate HIV-1 LTR via vFLIP K13-induced classical NF-κB pathway which cooperates with HIV-1 Tat protein.
Comparative context analysis of codon pairs on an ORFeome scale
Authors: Moura Gabriela , Pinheiro Miguel , Silva Raquel , Miranda Isabel , Afreixo Vera , Dias Gaspar , Freitas Adelaide , Oliveira José L , Santos Manuel AS
Published: February 2005

Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context.
Nuclear localization is required for Dishevelled function in Wnt/β-catenin signaling
Authors: Itoh Keiji , Brott Barbara K , Bae Gyu-Un , Ratcliffe Marianne J , Sokol Sergei Y
Published: February 2005

Background

Dishevelled (Dsh) is a key component of multiple signaling pathways that are initiated by Wnt secreted ligands and Frizzled receptors during embryonic development. Although Dsh has been detected in a number of cellular compartments, the importance of its subcellular distribution for signaling remains to be determined.

Results

We report that Dsh protein accumulates in cell nuclei when Xenopus embryonic explants or mammalian cells are incubated with inhibitors of nuclear export or when a specific nuclear-export signal (NES) in Dsh is disrupted by mutagenesis. Dsh protein with a mutated NES, while predominantly nuclear, remains fully active in its ability to stimulate canonical Wnt signaling. Conversely, point mutations in conserved amino-acid residues that are essential for the nuclear localization of Dsh impair the ability of Dsh to activate downstream targets of Wnt signaling. When these conserved residues of Dsh are replaced with an unrelated SV40 nuclear localization signal, full Dsh activity is restored. Consistent with a signaling function for Dsh in the nucleus, treatment of cultured mammalian cells with medium containing Wnt3a results in nuclear accumulation of endogenous Dsh protein.

Conclusions

These findings suggest that nuclear localization of Dsh is required for its function in the canonical Wnt/β-catenin signaling pathway. We discuss the relevance of these findings to existing models of Wnt signal transduction to the nucleus.
Infant‐Directed Speech Facilitates Word Segmentation
Authors: Thiessen Erik D. , Hill Emily A. , Saffran Jenny R.
Published: February 2005

There are reasons to believe that infant‐directed (ID) speech may make language acquisition easier for infants. However, the effects of ID speech on infants' learning remain poorly understood. The experiments reported here assess whether ID speech facilitates word segmentation from fluent speech. One group of infants heard a set of nonsense sentences spoken with intonation contours characteristic of adult‐directed (AD) speech, and the other group heard the same sentences spoken with intonation contours characteristic of ID speech. In both cases, the only cue to word boundaries was the statistical structure of the speech. Infants were able to distinguish words from syllable sequences spanning word boundaries after exposure to ID speech but not after hearing AD speech. These results suggest that ID speech facilitates word segmentation and may be useful for other aspects of language acquisition as well. Issues of direction of preference in preferential listening paradigms are also considered.
Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition
Authors: Maeda Masato , Johnson Keith R. , Wheelock Margaret J.
Published: February 2005

Epithelium-to-mesenchyme transitions (EMTs) are characterized by morphological and behavioral changes in cells. During an EMT, E-cadherin is downregulated while N-cadherin is upregulated. The goal of this study was to understand the role cadherin switching plays in EMT using a classical model system: transforming growth factor β1 (TGF-β1)-mediated EMT in mammary epithelial cells. We showed that stress fibers and focal adhesions are increased, and cell-cell junctions are decreased in response to TGF-β1. Moreover, these changes were reversible upon removal of TGF-β1. Downregulation of E-cadherin and upregulation of N-cadherin were both transcriptional. Neither experimental knockdown nor experimental overexpression of N-cadherin interfered with the morphological changes. In addition, the morphological changes associated with EMT preceded the downregulation of E-cadherin. Interestingly, TGF-β1-induced motility in N-cadherin-knockdown cells was significantly reduced. Together, these data suggest that cadherin switching is necessary for increased motility but is not required for the morphological changes that accompany EMT.
CD98 modulates integrin β1 function in polarized epithelial cells
Authors: Cai Songmin , Bulus Nada , Fonseca-Siesser Priscila M. , Chen Dong , Hanks Steven K. , Pozzi Ambra , Zent Roy
Published: February 2005

The type II transmembrane protein CD98, best known as the heavy chain of the heterodimeric amino acid transporters (HAT), is required for the surface expression and basolateral localization of this transporter complex in polarized epithelial cells. CD98 also interacts with β1 integrins resulting in an increase in their affinity for ligand. In this study we explored the role of the transmembrane and cytoplasmic domains of CD98 on integrin-dependent cell adhesion and migration in polarized renal epithelial cells. We demonstrate that the transmembrane domain of CD98 was sufficient, whereas the five N-terminal amino acids of this domain were required for CD98 interactions with β1 integrins. Overexpression of either full-length CD98 or CD98 lacking its cytoplasmic tail increased cell adhesion and migration, whereas deletion of the five N-terminal amino acids of the transmembrane domain of CD98 abrogated this effect. CD98 and mutants that interacted with β1 integrins increased both focal adhesion formation and FAK and AKT phosphorylation. CD98-induced cell adhesion and migration was inhibited by addition of phosphoinositol 3-OH kinase (PI3-K) inhibitors suggesting these cell functions are PI3-K-dependent. Finally, CD98 and mutants that interacted with β1, induced marked changes in polarized renal epithelial cell branching morphogenesis in collagen gels. Thus, in polarized renal epithelial cells, CD98 might be viewed as a scaffolding protein that interacts with basolaterally expressed amino acid transporters and β1 integrins and can alter diverse cellular functions such as amino acid transport as well as cell adhesion, migration and branching morphogenesis.
Chagasin, the endogenous cysteine-protease inhibitor ofTrypanosoma cruzi, modulates parasite differentiation and invasion of mammalian cells
Authors: Santos Camila C. , Sant'Anna Celso , Terres Amanda , Cunha-e-Silva Narcisa L. , Scharfstein Julio , de A. Lima Ana Paula C.
Published: February 2005

Chagasin is a Trypanosoma cruzi protein that was recently characterized as a tight-binding inhibitor of papain-like cysteine proteases (CPs). Considering that parasite virulence and morphogenesis depend on the endogenous activity of lysosomal CPs of the cruzipain family, we sought to determine whether chagasin and cruzipain interact in the living cell. Ultrastructural studies showed that chagasin and cruzipain both localize to the Golgi complex and reservosomes (lysosome-like organelles), whereas free chagasin was found in small intracellular vesicles, suggesting that chagasin trafficking pathways might intersect with those of cruzipain. Taking advantage of the fact that sodium dodecyl sulphate and β-mercaptoethanol prevent binding between the isolated proteins but do not dismantle preformed cruzipain-chagasin complexes, we obtained direct evidence that chagasin-cruzipain complexes are indeed formed in epimastigotes. Chagasin transfectants (fourfold increase in CP inhibitory activity) displayed low rates of differentiation (metacyclogenesis) and exhibited increased resistance to a synthetic CP inhibitor. These phenotypic changes were accompanied by a drastic reduction of soluble cruzipain activity and by upregulated secretion of cruzipain-chagasin molecular complexes. Analysis of six T. cruzi strains revealed that expression levels of cruzipain and chagasin are variable, but the molar ratios are fairly stable (∼50:1) in most strains, with the exception of the G strain (5:1), which is poorly infective. On the same vein, we found that trypomastigotes overexpressing chagasin are less infective than wild-type parasites in vitro. The deficiency of chagasin overexpressers is caused by lower activity of membrane-associated CPs, because membranes recovered from wild-type trypomastigotes restored infectivity and this effect was nullified by the CP inhibitor E-64. In summary, our studies suggest that chagasin regulates the endogenous activity of CP, thus indirectly modulating proteolytic functions that are essential for parasite differentiation and invasion of mammalian cells.
Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo
Authors: Kim-Kaneyama Joo-ri , Suzuki Wataru , Ichikawa Kiyoko , Ohki Takahiro , Kohno Yoko , Sata Masataka , Nose Kiyoshi , Shibanuma Motoko
Published: February 2005

Hic-5 is a focal adhesion protein belonging to the paxillin LIM family that shuttles in and out of the nucleus. In the present study, we examined the expression of Hic-5 among mouse tissues by immunohistochemistry and found its expression only in smooth-muscle cells in several tissues. This result is consistent with a previous report on adult human tissues and contradicts the relatively ubiquitous expression of paxillin, the protein most homologous to Hic-5. One factor characterizing smooth-muscle cells in vivo is a continuous exposure to mechanical stretching in the organs. To study the involvement of Hic-5 in cellular responses to mechanical stress, we exposed mouse embryo fibroblasts to a uni-axial cyclic stretching and found that Hic-5 was relocalized from focal adhesions to stress fibers through its C-terminal LIM domains during the stress. In sharp contrast to this, paxillin did not change its focal-adhesion-based localization. Of the factors tested, which included interacting partners of Hic-5, only CRP2 (an only-LIM protein expressed in vascular smooth-muscle cells) and GIT1 were, like Hic-5, localized to stress fibers during the cyclic stretching. Interestingly, Hic-5 showed a suppressive effect on the contractile capability of cells embedded in three-dimensional collagen gels, and the effect was further augmented when CRP2 co-localized with Hic-5 to fiber structures of those cells. These results suggested that Hic-5 was a mediator of tensional force, translocating directly from focal adhesions to actin stress fibers upon mechanical stress and regulating the contractile capability of cells in the stress fibers.
Inositol (1,4,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells
Authors: Turvey Matthew R. , Fogarty Kevin E. , Thorn Peter
Published: February 2005

We explored a potential structural and functional link between filamentous actin (F-actin) and inositol (1,4,5)-trisphosphate receptors (IP3Rs) in mouse pancreatic acinar cells. Using immunocytochemistry, F-actin and type 2 and 3 IP3Rs (IP3R2 and IP3R3) were identified in a cellular compartment immediately beneath the apical plasma membrane. In an effort to demonstrate that IP3R distribution is dependent on an intact F-actin network in the apical subplasmalemmal region, cells were treated with the actin-depolymerising agent latrunculin B. Immunocytochemistry indicated that latrunculin B treatment reduced F-actin in the basolateral subplasmalemmal compartment, and reduced and fractured F-actin in the apical subplasmalemmal compartment. This latrunculin-B-induced loss of F-actin in the apical region coincided with a reduction in IP3R2 and IP3R3, with the remaining IP3Rs localized with the remaining F-actin. Experiments using western blot analysis showed that IP3R3s are resistant to extraction by detergents, which indicates a potential interaction with the cytoskeleton. Latrunculin B treatment in whole-cell patch-clamped cells inhibited Ca2+-dependent Cl– current spikes evoked by inositol (2,4,5)-trisphosphate; this is due to an inhibition of the underlying local Ca2+ signal. Based on these findings, we suggest that IP3Rs form links with F-actin in the apical domain and that these links are essential for the generation of local Ca2+ spikes.
Improved Thermal Stability of Europium Complex Nanoclusters Embedded in Silica Colloidal Spheres
Authors: Zhao Dan , Qin Weiping , Zhang Jisen , De Gejihu , Zhang Jishuang
Published: February 2005

Europium complex nanoclusters are introduced into monodisperse colloidal silica spheres by a modified Stöber method. Transmission electron microscopy measurements confirm that the hybrid spheres possess smooth surface and core-shell structure. The hybrid spheres display strong characteristic luminescence of the Eu3+ ions. Furthermore they exhibit an improved thermal stability compared with the pure rare earth (RE) complex.
Vanadium-catalyzed Isomerization of Cyclopropanemethanols to Homoallylic Alcohols Involving C–C Bond Cleavage
Authors: Maeda Yasunari , Nishimura Takahiro , Uemura Sakae
Published: February 2005

Some vanadium compounds work as effective catalysts for isomerization of cyclopropanemethanols to the corresponding homoallylic alcohols. This reaction may proceed via [3,3]sigmatropic rearrangement involving an oxovanadium cyclopropane-methanolate accompanied by the C–C bond cleavage.
Fabrication of MgO Hierarchical Nanostructures by a Thermal Evaporation Method
Authors: Yan Peng , Ye Changhui , Fang Xiaosheng , Zhao Jianwei , Wang Zhenyang , Zhang Lide
Published: February 2005

MgO hierarchical nanostructures were prepared through a simple thermal evaporation method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images reveal the 4-fold symmetric MgO hierarchical morphologies. These structures may be helpful in studies of nanostructure growth mechanisms and find applications in numerous fields.