bluuebunny/crossref_metadata_2025 huggingface dataset:
Species Specificity in Ribosome Biogenesis: a Nonconserved Phosphoprotein Is Required for Formation of the Large Ribosomal Subunit in
Trypanosoma brucei
Authors: Jensen Bryan C. , Brekken Deirdre L. , Randall Amber C. , Kifer Charles T. , Parsons Marilyn
Published: January 2005

In the protozoan parasite
Trypanosoma brucei
, the large rRNA, which is a single 3.4- to 5-kb species in most organisms, is further processed to form six distinct RNAs, two larger than 1 kb (LSU1 and LSU2) and four smaller than 220 bp. The small rRNA SR1 separates the two large RNAs, while the remaining small RNAs are clustered at the 3′ end of the precursor rRNA. One would predict that
T. brucei
possesses specific components to carry out these added processing events. We show here that the trypanosomatid-specific nucleolar phosphoprotein NOPP44/46 is involved in this further processing. Cells depleted of NOPP44/46 by RNA interference had a severe growth defect and demonstrated a defect in large-ribosomal-subunit biogenesis. Concurrent with this defect, a significant decrease in processing intermediates, particularly for SR1, was seen. In addition, we saw an accumulation of aberrant processing intermediates caused by cleavage within either LSU1 or LSU2. Though it is required for large-subunit biogenesis, we show that NOPP44/46 is not incorporated into the nascent particle. Thus, NOPP44/46 is an unusual protein in that it is both nonconserved and required for ribosome biogenesis.
Cryptococcus neoformansMitochondrial Superoxide Dismutase: an Essential Link between Antioxidant Function and High-Temperature Growth
Authors: Giles Steven S. , Batinić-Haberle Ines , Perfect John R. , Cox Gary M.
Published: January 2005

Manganese superoxide dismutase is an essential component of the mitochondrial antioxidant defense system of most eukaryotes. In the present study, we used a reverse-genetics approach to assess the contribution of theCryptococcus neoformansmanganese superoxide dismutase (Sod2) for antioxidant defense. Strains with mutations in theSOD2gene exhibited increased susceptibility to oxidative stress as well as poor growth at elevated temperatures compared to isogenic wild-type strains. Thesod2Δ mutants were also avirulent in a murine model of inhaled cryptococcosis. Reconstitution of asod2Δ mutant restored Sod2 activity, eliminated the oxidative stress and temperature-sensitive (ts) phenotypes, and complemented the virulence phenotype. Characterization of the ts phenotype revealed a dependency between Sod2 antioxidant activity and the ability ofC. neoformanscells to adapt to growth at elevated temperatures. The ts phenotype could be suppressed by the addition of either ascorbic acid (10 mM) or Mn salen (200 μM) at 30°C, but not at 37°C. Furthermore,sod2Δ mutant cells that were incubated for 24 h at 37°C under anaerobic, but not aerobic, conditions were viable when shifted to the permissive conditions of 25°C in the presence of air. These data suggest that theC. neoformansSod2 is a major component of the antioxidant defense system in this human fungal pathogen and that adaptation to growth at elevated temperatures is also dependent on Sod2 activity.
Loss of Meiotic Rereplication Block in
Saccharomyces cerevisiae
Cells Defective in Cdc28p Regulation
Authors: Rice Lyndi M. , Plakas Constantine , Nickels Joseph T.
Published: January 2005

Cdc28p is the major cyclin-dependent kinase in
Saccharomyces cerevisiae
. Its activity is required for blocking the reinitiation of DNA replication during mitosis. Here, we show that under conditions where Cdc28p activity is improperly regulated—either through the loss of function of the
Schizosaccharomyces pombe wee1
ortholog Swe1p or through the expression of a dominant
CDC28
allele,
CDC28AF
—diploid yeast cells are able to complete several rounds of premeiotic DNA replication within a single meiotic cell cycle. Moreover, a percentage of mutant cells exhibit a “multispore” phenotype, possessing the ability to package more than four spores within a single ascus. These multispored asci contain both even and odd numbers of viable spores. In order for meiotic rereplication and multispore formation to occur, cells must initiate homologous recombination and maintain proper chromosome cohesion during meiosis I. Rad9p- or Rad17p-dependent checkpoint mechanisms are not required for multispore formation and neither are the B-type cyclin Clb6p and the cyclin-dependent kinase inhibitor Sic1p. Finally, we present evidence of a possible role for a Cdc55p-dependent protein phosphatase 2A in initiating meiotic replication.
Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth
Authors: Zurita-Martinez Sara A. , Cardenas Maria E.
Published: January 2005

In the budding yeast
Saccharomyces cerevisiae
, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.
Exposure of Cells to a Cell Number-Counting Factor Decreases the Activity of Glucose-6-Phosphatase To Decrease Intracellular Glucose Levels in
Dictyostelium discoideum
Authors: Jang Wonhee , Gomer Richard H.
Published: January 2005

The development of
Dictyostelium discoideum
is a model for tissue size regulation, as these cells form groups of ≈2 × 10
4
cells. The group size is regulated in part by a negative feedback pathway mediated by a secreted multipolypeptide complex called counting factor (CF). CF signal transduction involves decreasing intracellular CF glucose levels. A component of CF, countin, has the bioactivity of the entire CF complex, and an 8-min exposure of cells to recombinant countin decreases intracellular glucose levels. To understand how CF regulates intracellular glucose, we examined the effect of CF on enzymes involved in glucose metabolism. Exposure of cells to CF has little effect on amylase or glycogen phosphorylase, enzymes involved in glucose production from glycogen. Glucokinase activity (the first specific step of glycolysis) is inhibited by high levels of CF but is not affected by an 8-min exposure to countin. The second enzyme specific for glycolysis, phosphofructokinase, is not regulated by CF. There are two corresponding enzymes in the gluconeogenesis pathway, fructose-1,6-bisphosphatase and glucose-6-phosphatase. The first is not regulated by CF or countin, whereas glucose-6-phosphatase is regulated by both CF and an 8-min exposure to countin. The countin-induced changes in the

K
m

and
V
max
of glucose-6-phosphatase cause a decrease in glucose production that can account for the countin-induced decrease in intracellular glucose levels. It thus appears that part of the CF signal transduction pathway involves inhibiting the activity of glucose-6-phosphatase, decreasing intracellular glucose levels and affecting the levels of other metabolites, to regulate group size.
Broad Sensitivity of
Saccharomyces cerevisiae
Lacking Ribosome-Associated Chaperone Ssb or Zuo1 to Cations, Including Aminoglycosides
Authors: Kim So-Young , Craig Elizabeth A.
Published: January 2005

The Hsp70 Ssb and J protein Zuo1 of
Saccharomyces cerevisiae
are ribosome-associated molecular chaperones, proposed to be involved in the folding of newly synthesized polypeptide chains. Cells lacking Ssb and/or Zuo1 have been reported to be hypersensitive to cationic aminoglycoside protein synthesis inhibitors that affect translational fidelity and to NaCl. Since we found that Δ
ssb1
Δ
ssb2
(Δ
ssb1
,
2
), Δ
zuo1
, and wild-type cells have very similar levels of translational misreading in the absence of aminoglycosides, we asked whether the sensitivities to aminoglycosides and NaCl represent a general increase in sensitivity to cations. We found that Δ
ssb1
,
2
and Δ
zuo1
cells are hypersensitive to a wide range of cations. This broad sensitivity is similar to that of cells having lowered activity of major plasma membrane transporters, such as the major K
+
transporters Trk1 and Trk2 or their regulators Hal4 and Hal5. Like Δ
hal4
,
5
cells, Δ
ssb1
,
2
and Δ
zuo1
cells have increased intracellular levels of Na
+
and Li
+
upon challenge with higher-than-normal levels of these cations, due to an increased rate of influx. In the presence of aminoglycosides, Δ
ssb1
,
2
, Δ
zuo1
, and Δ
hal 4
,
5
cells have similarly increased levels of translational misreading. We conclude that, in vivo, the major cause of the aminoglycoside sensitivity of cells lacking ribosome-associated molecular chaperones is a general increase in cation influx, perhaps due to altered maturation of membrane proteins.
The G
1
Cyclin Cln3 Regulates Morphogenesis in
Candida albicans
Authors: Chapa y Lazo Bernardo , Bates Steven , Sudbery Peter
Published: January 2005

In
Saccharomyces cerevisiae
, the G
1
cyclin Cln3 initiates the Start of a mitotic cell cycle in response to size and nutrient inputs. Loss of Cln3 delays but does not prevent Start, due to the eventual Cln3-independent transcription of
CLN1
and
CLN2.
When unbudded cells of the human pathogen
Candida albicans
were depleted of the G
1
cyclin Cln3 they increased in size but did not bud. Thus, unlike
S. cerevisiae
, Cln3 is essential for budding in
C. albicans.
However, eventually the large unbudded cells spontaneously produced filamentous forms. The morphology was growth medium dependent; on nutritionally poor medium the polarized outgrowths fulfilled the formal criteria for true hyphae. This state is stable, and continued growth leads to a hyphal mycelium, which invades the agar substratum. Interestingly, it is also required for normal hyphal development, as Cln3-depleted cells develop morphological abnormalities if challenged with hyphal inducing signals such as serum or neutral pH. Taken together, these results show that, in
C. albicans
, Cln3 has assumed a critical role in coordinating mitotic cell division with differentiation.
Cyclin Cln3p Links G
1
Progression to Hyphal and Pseudohyphal Development in
Candida albicans
Authors: Bachewich Catherine , Whiteway Malcolm
Published: January 2005

G
1
cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen
Candida albicans
, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G
1
cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G
1
, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of
CLN3
. In contrast, repressing
CLN3
in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G
1
cyclin can activate developmental pathways in
C. albicans
and uncouple differentiation from the normal environmental controls. The data suggest that the G
1
phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in
C. albicans
.
THEORETICAL STUDY OF NEUTRAL DIPOLAR ATOM IN WATER: STRUCTURE, SPECTROSCOPY AND FORMATION OF AN EXCITONIC STATE
Authors: SPEZIA RICCARDO , COUDERT FRANÇOIS-XAVIER , BOUTIN ANNE
Published: January 2005

We review theoretical studies on the properties of solvated neutral dipolar atoms. The combination use of mixed quantum classical molecular simulations and analytical mean-field dipolar excitonic state theory allows the rationalization of the experimental observations in terms of physical macroscopic properties. A very good agreement is observed between experiments, theory and simulations on the spectroscopic behavior of silver in water. Molecular simulations also give thermodynamic and kinetic information on the reduction reaction of the cation that leads to the neutral atom in an excitonic state.
WINNERLESS COMPETITION IN NETWORKS OF COUPLED MAP NEURONS
Authors: CASADO J. M. , IBARZ B. , SANJUÁN M. A. F.
Published: January 2005

The brain can be described as a very complex dynamical system whose autonomous, intrinsic activity is modulated by a great variety of external inputs. In the last decade, the simulation of this activity by using networks of neurons has led to the development of new approaches to describe the processing of information by the nervous system. In this review paper we focus on winnerless competition, a new concept allowing the analysis of the emergent behavior associated with collective synchronization, multi-stability and adaptation — properties which seem to be at the basis of brain performance. The relationship between winnerless competition and the concept of chaotic itinerancy is stressed by pointing out their common association with the formation of complex heteroclinic orbits in the high-dimensional phase space associated with the dynamics of complex neuronal systems. The potentialities of networks of coupled map neurons to the study of activation and synchronization regimes in neural systems are suggested by means of different simulations showing a great variety of dynamical phenomena.
GENERALIZATION OF CLASSICAL STATISTICAL MECHANICS TO QUANTUM MECHANICS AND STABLE PROPERTY OF CONDENSED MATTER
Authors: HUANG Y. C. , MA F. C. , ZHANG N.
Published: January 2005

Classical statistical average values are generally generalized to average values of quantum mechanics. It is discovered that quantum mechanics is a direct generalization of classical statistical mechanics, and we generally deduce both a new general continuous eigenvalue equation and a general discrete eigenvalue equation in quantum mechanics, and discover that a eigenvalue of quantum mechanics is just an extreme value of an operator in possibility distribution, the eigenvalue f is just classical observable quantity. A general classical statistical uncertain relation is further given, and the general classical statistical uncertain relation is generally generalized to the quantum uncertainty principle; the two lost conditions in classical uncertain relation and quantum uncertainty principle, respectively, are found. We generally expound the relations among the uncertainty principle, singularity and condensed matter stability, discover that the quantum uncertainty principle prevents the appearance of singularity of the electromagnetic potential between nucleus and electrons, and give the failure conditions of the quantum uncertainty principle. Finally, we discover that the classical limit of quantum mechanics is classical statistical mechanics, the classical statistical mechanics may further be degenerated to classical mechanics and we discover that merely stating that the classical limit of quantum mechanics is classical mechanics is a mistake. As application examples, we deduce both the Schrödinger equation and the state superposition principle, and deduce that there exists a decoherent factor from a general mathematical representation of the state superposition principle; the consistent difficulty between statistical interpretation of quantum mechanics and determinant property of classical mechanics is overcome.
OVERCOMING THE BARRIERS TO EAST WEST TRADE: EXPORT SUCCESS FACTORS OF ENTREPRENEURIAL AUSTRALIAN RECORD COMPANIES
Authors: ALEXOPOULOS ALEXANDER , COULTHARD MAX , TERZIOVSKI MILÉ
Published: January 2005

This exploratory research utilised the Lumpkin and Dess (1996) Entrepreneurial Orientation (EO) construct, as a means of characterising the extent to which Australian music recording companies were entrepreneurial. Utilising the five EO dimensions, the study found those record companies that had a moderate to high entrepreneurial rating tended to be high export performers. Best practice companies were identified and a profile of some key export success factors developed. Overall, this study provides a sound starting point for business practitioners wanting to review the impact of their entrepreneurial orientation in an international setting.
COMPARISON OF BUSINESS START-UPS IN A TRANSITION ECONOMY AND IN A TRADITIONAL MARKET ECONOMY: THE CASE OF THE CZECH REPUBLIC AND AUSTRIA
Authors: MUGLER JOSEF , KESSLER ALEXANDER
Published: January 2005

This research compares business start-ups in two neighboring countries in Central Europe: Austria, with its traditional market economy, and the Czech Republic, with its recently developed market economy. A joint questionnaire (derived from the Vienna Entrepreneurship Studies) which was only marginally modified for the specifics of the two countries allowed a number of comparisons between 627 newly established businesses in Austria and 778 such businesses in the Czech Republic. The concept for these comparisons was based on a comprehensive view of configurations consisting of the entrepreneur's personality, resources, environment, and the start-up process. For both countries, a typically successful configuration of these dimensions was pre-defined and used as a reference for the measurement of deviations (effect sizes). On the basis of these effect sizes, it was then possible to detect clusters of configurations in both countries. The cluster solutions show remarkable similarities on an aggregated level, bringing to light at least two easily comparable clusters for each country. However, they do indicate many significant differences at the individual aspect level. In addition, an overall comparison of the Austrian and Czech clusters revealed clear differences in the characteristics of start-ups in a traditional market economy and a young market economy.
A CASE STUDY OF CULTURE INNOVATION FOR VIRTUAL ENTERPRISE IN CHINA
Authors: SONG FAN , YUAN LI
Published: January 2005

Abstract Virtual enterprise exists in a higher organizational form when economy develops to some stages. This paper analyzes the operational characters of organization and behavior between traditional enterprise and virtual one. Based on the special features, a close-loop system model of culture innovation for virtual enterprise is established from point of view in System Science. It is recognized that culture force is the most powerful and significant core competence in virtual enterprise. The key five steps of culture innovation are presented and three situations on flexible culture management of virtual enterprise are stated in the paper. In addition to the survey research, we conducted an in-depth case study of China. The successful reasons for the enterprise culture innovation in virtual enterprise and their alliance are finally discussed with the actual case "New Era" in China. Our case study validates some of these findings in small- and medium-sized virtual enterprise. Implications for practice as well as study are provided.
PERCEPTUALLY ADAPTIVE VIDEO WATERMARKING USING MOTION ESTIMATION
Authors: ECHIZEN ISAO , FUJII YASUHIRO , YAMADA TAKAAKI , TEZUKA SATORU , YOSHIURA HIROSHI
Published: January 2005

Video watermarks must maintain picture quality and withstand image processing, and resolving the tradeoff between these conflicting requirements has been one of the central problems in research on video watermarking. This paper shows that watermarks are less perceptible where picture contents are moving and proposes a new criterion for measuring watermark imperceptibility from motion vectors and deformation quantities. It also proposes a watermarking method that uses this criterion to allocate watermarks to picture areas adaptively. Experimental evaluation showed that the proposed method reduces degradation in picture quality and that, for the same picture quality after MPEG encoding and decoding, between 30% and 40% more watermarks can be embedded, improving detection reliability after MPEG processing by an average of 9.5%. The proposed method would be most effective when used with MPEG encoders because they already have the necessary motion estimation functions.
COVER NOISE INTERFERENCE SUPPRESSION IN MULTIMEDIA DATA HIDING
Authors: GANG LITAO , AKANSU ALI N.
Published: January 2005

In this paper, we investigate the general problem of data hiding and propose an approach for effective cover noise interference rejection in oblivious applications. We first evaluate the performance in the commonly used direct sequence modulation approach where a low-power signal is embedded into the original cover signal. The optimal detection is derived and its performance is analyzed. Second, we study a novel approach in oblivious data hiding and evaluate its performance and compare it with existing algorithms. Both simulation studies and empirical data hiding results validate its efficiency in the multimedia oblivious applications.
LEONARD PAIRS AND THE ASKEY–WILSON RELATIONS
Authors: TERWILLIGER PAUL , VIDUNAS RAIMUNDAS
Published: January 2005

Let K denote a field and let V denote a vector space over K with finite positive dimension. We consider an ordered pair of linear transformations A:V→V and A*:V→V which satisfy the following two properties:

(i) There exists a basis for V with respect to which the matrix representing A is irreducible tridiagonal and the matrix representing A* is diagonal.

(ii) There exists a basis for V with respect to which the matrix representing A* is irreducible tridiagonal and the matrix representing A is diagonal.

We call such a pair a Leonard pair on V. Referring to the above Leonard pair, we show there exists a sequence of scalars β,γ,γ*,ϱ,ϱ*,ω,η,η* taken from K such that both [Formula: see text] The sequence is uniquely determined by the Leonard pair provided the dimension of V is at least 4. The equations above are called the Askey–Wilson relations.
MULTIPLE TRANSITIVITY AND MIN-WISE INDEPENDENCE IN PERMUTATION GROUPS
Authors: FRANCHI C.
Published: January 2005

Let Ω be a finite linearly ordered set and let k be a positive integer. A permutation group G on Ω is called co-k-restricted min-wise independent on Ω if [Formula: see text] for any X⊆Ω such that |X|≥|Ω|-k+1 and for any x∈X. We show that co-k-restricted min-wise independent groups are exactly the groups with the property that for each subset X⊆Ω with |X|≤k-1, the stabilizer G{X} of X in G is transitive on Ω\X. Using this fact, we determine all co-k-restricted min-wise independent groups.
A CHARACTERIZATION OF ALTERNATING GROUPS BY ORDERS OF SOLVABLE SUBGROUPS
Authors: BI JIANXING , LI XIANHUA
Published: January 2005

In this paper, we prove that a finite group G is isomorphic to the alternating group An with n≥5 if and only if they have the same set of the orders of solvable subgroups.
LAKES BENEATH THE ICE SHEET: The Occurrence, Analysis, and Future Exploration of Lake Vostok and Other Antarctic Subglacial Lakes
Authors: Siegert Martin J.
Published: January 2005

▪ Abstract  Airborne geophysics has been used to identify more than 100 lakes beneath the ice sheets of Antarctica. The largest, Lake Vostok, is more than 250 km in length and 1 km deep. Subglacial lakes occur because the ice base is kept warm by geothermal heating, and generated meltwater collects in topographic hollows. For lake water to be in equilibrium with the ice sheet, its roof must slope ten times more than the ice sheet surface. This slope causes differential temperatures and melting/freezing rates across the lake ceiling, which excites water circulation. The exploration of subglacial lakes has two goals: to find and understand the life that may inhabit these unique environments and to measure the climate records that occur in sediments on lake floors. The technological developments required for in situ measurements mean, however, that direct studies of subglacial lakes may take several years to happen.
Calcium-independent phospholipase A2 is regulated by a novel protein kinase C in human coronary artery endothelial cells
Authors: Meyer Maureen C. , Kell Pamela J. , Creer Michael H. , McHowat Jane
Published: January 2005

We demonstrated previously that thrombin stimulation of endothelial cells activates a membrane-associated, Ca2+-independent phospholipase A2 (iPLA2) that selectively hydrolyzes arachidonylated plasmalogen phospholipids. We report that incubation of human coronary artery endothelial cells (HCAEC) with phorbol 12-myristate 13-acetate (PMA) to activate protein kinase C (PKC) resulted in hydrolysis of cellular phospholipids similar to that observed with thrombin stimulation (0.05 IU/ml; 10 min). Thrombin stimulation resulted in a decrease in arachidonylated plasmenylcholine (2.7 ± 0.1 vs. 5.3 ± 0.4 nmol PO4/mg of protein) and plasmenylethanolamine (7.5 ± 1.0 vs. 12.0 ± 0.9 nmol PO4/mg of protein). Incubation with PMA resulted in decreases in arachidonylated plasmenylcholine (3.2 ± 0.3 nmol PO4/mg of protein) and plasmenylethanolamine (6.0 ± 1.0 nmol PO4/mg of protein). Incubation of HCAEC with the selective iPLA2 inhibitor bromoenol lactone (5 mM; 10 min) inhibited accelerated plasmalogen phospholipid hydrolysis in response to both PMA and thrombin stimulation. Incubation of HCAEC with PMA (100 nM; 5 min) resulted in increased arachidonic acid release (7.1 ± 0.3 vs. 1.1 ± 0.1%) and increased production of lysoplasmenylcholine (1.4 ± 0.2 vs. 0.6 ± 0.1 nmol PO4/mg of protein), similar to the responses observed with thrombin stimulation. Downregulation of PKC by prolonged exposure to PMA (100 nM; 24 h) completely inhibited thrombin-stimulated increases in arachidonic acid release (7.1 ± 0.6 to 0.5 ± 0.1%) and lysoplasmenylcholine production (2.0 ± 0.1 to 0.2 ± 0.1 nmol PO4/mg of protein). These data suggest that PKC activates iPLA2 in HCAEC, leading to accelerated plasmalogen phospholipid hydrolysis and increased phospholipid metabolite production.
Force transmission, compliance, and viscoelasticity are altered in the α7-integrin-null mouse diaphragm
Authors: Lopez M. A. , Mayer U. , Hwang W. , Taylor T. , Hashmi M. A. , Jannapureddy S. R. , Boriek Aladin M.
Published: January 2005

α7β1 integrin is a transmembrane structural and receptor protein of skeletal muscles, and the absence of α7-integrin causes muscular dystrophy. We hypothesized that the absence of α7-integrin alters compliance and viscoelasticity and disrupts the mechanical coupling between passive transverse and axial contractile elements in the diaphragm. In vivo the diaphragm is loaded with pressure, and therefore axial and transverse length-tension relationships are important in assessing its function. We determined diaphragm passive length-tension relationships and the viscoelastic properties of its muscle in 1-month-old α7-integrin-null mice and age-matched controls. Furthermore, we measured the isometric contractile properties of the diaphragm from mutant and normal mice in the absence and presence of passive force applied in the transverse direction to fibers in 1-month-old and 5-month-old mutant mice. We found that compared with controls, the diaphragm direction of α7-integrin-null mutants showed 1) a significant decrease in muscle extensibility in 1-year-old mice, whereas muscle extensibility increased in the 1-month-old mice; 2) altered muscle viscoelasticity in the transverse direction of the muscle fibers of 1-month-old mice; 3) a significant increase in force-generating capacity in the diaphragms of 1-month-old mice, whereas in 5-month-old mice muscle contractility was depressed; and 4) significant reductions in mechanical coupling between longitudinal and transverse properties of the muscle fibers of 1-month-old mice. These findings suggest that α7-integrin serves an important mechanical function in the diaphragm by contributing to passive compliance, viscoelasticity, and modulation of its muscle contractile properties.
Insulin in methionine and homocysteine kinetics in healthy humans: plasma vs. intracellular models
Authors: Tessari Paolo , Kiwanuka Edward , Coracina Anna , Zaramella Michela , Vettore Monica , Valerio Anna , Garibotto Giacomo
Published: January 2005

Methionine is a sulfur-containing amino acid that is reversibly converted into homocysteine. Homocysteine is an independent cardiovascular risk factor frequently associated with the insulin resistance syndrome. The effects of insulin on methionine and homocysteine kinetics in vivo are not known. Six middle-aged male volunteers were infused with l-[ methyl-2H3,1-13C]methionine before (for 3 h) and after (for 3 additional hours) an euglycemic hyperinsulinemic (150 mU/l) clamp. Steady-state methionine and homocysteine kinetics were determined using either plasma (i.e., those of methionine) or intracellular (i.e., those of plasma homocysteine) enrichments. By use of plasma enrichments, insulin decreased methionine rate of appearance (Ra; both methyl- and carbon Ra) by 25% ( P < 0.003 vs. basal) and methionine disposal into proteins by 50% ( P < 0.0005), whereas it increased homocysteine clearance by ∼70% ( P < 0.025). With intracellular enrichments, insulin increased all kinetic rates, mainly because homocysteine enrichment decreased by ∼40% ( P < 0.001). In particular, transmethylation increased sixfold ( P < 0.02), transsulfuration fourfold ( P = 0.01), remethylation eightfold ( P < 0.025), and clearance eightfold ( P < 0.004). In summary, 1) physiological hyperinsulinemia stimulated homocysteine metabolic clearance irrespective of the model used; and 2) divergent changes in plasma methionine and homocysteine enrichments were observed after hyperinsulinemia, resulting in different changes in methionine and homocysteine kinetics. In conclusion, insulin increases homocysteine clearance in vivo and may thus prevent homocysteine accumulation in body fluids. Use of plasma homocysteine as a surrogate of intracellular methionine enrichment, after acute perturbations such as insulin infusion, needs to be critically reassessed.
NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice
Authors: Luiking Yvette C. , Hallemeesch Marcella M. , Lamers Wouter H. , Deutz Nicolaas E. P.
Published: January 2005

Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino acid and protein kinetics are regulated by NO synthesized by nitric oxide synthase-2 or -3 (NOS2 or NOS3), we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2−/−), and NOS3-deficient (NOS3−/−) mice under control (unstimulated) and lipopolysaccharide (LPS)-treated conditions. Muscle amino acid metabolism was studied across the hindquarter by infusing the stable isotopes l-[ ring-2H5]phenylalanine, l-[ ring-2H2]tyrosine, l-[ guanidino-15N2]arginine, and l-[ ureido-13C,2H2]citrulline. Muscle blood flow was measured using radioactive p-aminohippuric acid dilution. Under baseline conditions, muscle blood flow was halved in NOS2−/− mice ( P < 0.1), with simultaneous reductions in muscle glutamine, glycine, alanine, arginine release and glutamic acid, citrulline, valine, and leucine uptake ( P < 0.1). After LPS treatment, (net) muscle protein synthesis increased in WT and NOS2−/− mice [LPS vs. control: 13 ± 3 vs. 8 ± 1 (SE) nmol·10 g−1·min−1 (WT), 18 ± 5 vs. 7 ± 2 nmol·10 g−1·min−1 (NOS2−/−); P < 0.05 for LPS vs. control]. This response was absent in NOS3−/− mice (LPS vs. control: 11 ± 4 vs. 10 ± 2 nmol·10 g−1·min−1). In agreement, the increase in muscle arginine turnover after LPS was also absent in NOS3−/− mice. In conclusion, disruption of the NOS2 gene compromises muscle glutamine release and muscle blood flow in control mice, but had only minor effects after LPS. NOS3 activity is crucial for the increase in muscle arginine and protein turnover during early endotoxemia.
Depletion of Endothelial Progenitor Cells in the Peripheral Blood of Patients With Rheumatoid Arthritis
Authors: Grisar Johannes , Aletaha Daniel , Steiner Carl W. , Kapral Theresa , Steiner Sabine , Seidinger Daniela , Weigel Günter , Schwarzinger Ilse , Wolozcszuk Wolfgang , Steiner Günter , Smolen Josef S.
Published: January 2005

Background—

Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA.

Methods and Results—

EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (n=36) and low disease activity (n=16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay. EPCs were significantly decreased in RA patients suffering from active disease compared with those from HRs, as measured by FACS analysis (0.026±0.002% versus 0.045±0.008%, respectively,
P
<0.05), CFU assay (mean of 5±2 versus 18±5 CFU/well in HRs,
P
<0.05), and CAC assay (mean of 7±2 versus 52±16 positive cells/high-power field,
P
<0.005). In contrast, the frequency of circulating EPCs from patients with low disease activity was comparable to that of healthy individuals (0.052±0.006% by FACS analysis), CFU assay (10±5 CFU/well), and CAC assay (mean of 25±5 positive cells). Moreover, EPC quantities in peripheral blood were correlated inversely with disease activity as assessed by the disease activity score (
r
=−0.38,
P
<0.01).

Conclusions—

Our observations indicate that active RA is associated with a depletion of circulating EPCs. This might be one of several factors contributing to the increased cardiovascular risk in RA.
Targeted Modification of Atrial Electrophysiology by Homogeneous Transmural Atrial Gene Transfer
Authors: Kikuchi Kan , McDonald Amy D. , Sasano Tetsuo , Donahue J. Kevin
Published: January 2005

Background—

Safe and effective myocardial gene transfer remains elusive. Heterogeneous ventricular gene delivery has been achieved in small mammals but generally with methods not readily transferable to the clinic. Atrium-specific gene transfer has not yet been reported. We hypothesized that homogeneous atrial gene transfer could be achieved by direct application of adenoviral vectors to the epicardial surface, use of poloxamer gel to increase virus contact time, and mild trypsinization to increase virus penetration.

Methods and Results—

We “painted” recombinant adenovirus encoding the reporter gene
Escherichia coli
β-galactosidase directly onto porcine atria. Investigational variables included poloxamer use, trypsin concentration, and safety. Using the painting method, we modified the atrial phenotype with an adenovirus expressing HERG-G628S, a long-QT-syndrome mutant. Our results showed that application of virus with poloxamer alone resulted in diffuse epicardial gene transfer with negligible penetration into the myocardium. Dilute trypsin concentrations allowed complete transmural gene transfer. After trypsin exposure, echocardiographic left atrial diameter did not change. Left atrial function decreased on postoperative day 3 but returned to baseline by day 7. Tissue tensile strength was affected only in the 1% trypsin group. HERG-G628S gene transfer prolonged atrial action potential duration and refractory period without affecting ventricular electrophysiology.

Conclusions—

We show complete transmural atrial gene transfer by this novel painting method. Adaptation of the method could allow application to other tissue targets. Use with functional proteins in the atria could cure or even prevent diseases such as atrial fibrillation or sinus node dysfunction.
Denis Fonvizin and the Concept of Nobility: An Eighteenth-century Russian Echo of a Western Debate
Authors: Offord Derek
Published: January 2005

The article examines the contribution made by Denis Fonvizin, one of the major men of letters of the age of Catherine the Great, to debate about the status and function of the eighteenth-century Russian nobility. This contribution is set in the context of changes in the balance between the nobility’s obligations to the state and the privileges it enjoyed and in the context of contemporary court politics. Aware of western debates on the subject, Fonvizin approves of engagement by the nobility in commerce and prefers personal merit to heredity as a criterion for ennoblement and retention of noble status. He uses his conception of nobility (which is bolstered by the notions of virtue and honour that he draws from foreign sources) to perpetuate a sense of obligation among the Russian educated éite even though that élite had in 1762 ceased to be formally required to serve. At the same time he begins in effect to redirect the allegiance of the élite away from the state and towards the nation.
Agrarian Individualism, Collective Practices and the French Revolution: The Law of 10 June 1793 and the Partition of Common Land in the Department of the Gard
Authors: Plack Noelle L.
Published: January 2005

This article examines a key piece of social legislation during the French Revolution: the Jacobin decree of 10 June 1793, which authorized the partition of village common land throughout France. After a thorough review of the historiography to date, a case study of the department of the Gard in southern France is presented. Only a small number of villages in the Gard successfully partitioned their commons under this legislation, but the spirit of the Jacobin measure seems to have had a more profound effect. By extending the investigation into the Empire and examining the Napoleonic law of 9 Ventôse XII, the general effects of common land privatization become clear. At least a quarter of all communes in the Gard experienced a change to the tenure of the commons during the period 1793-1804. This shift in land use strengthened both traditional subsistence-based grain cultivation and more commercialized viticulture in the region.
Update on the Treatment of Infections in the Pediatric and Neonatal Intensive Care Unit
Authors: Marlowe Karen F.
Published: January 2005

Although many similarities exist between pediatric and adult critical care, several important distinctions should be made with regard to the treatment of infections. Any discussion of age-related consideration must take into account variations in the pharmacokinetics of antibiotics for infants and children. Important variations are seen in absorption, distribution, and excretion and must be considered in the determination of appropriate age-related dosing. Some variations also exist in patterns of expected flora, suspected pathogens, and patterns of resistance. This is true for both communityacquired illnesses and hospital-acquired infections. Finally, certain infections occur predominately or uniquely in neonates and children. This review addresses these 3main areas for both the pediatric and neonatal intensive care patient.
Short-Course Antimicrobial Therapy for the Treatment of Pneumonia
Authors: Pass Steven E. , Gearhart Michelle M. , Young Emily J.
Published: January 2005

Duration of antimicrobial therapy for the treatment of pneumonia has been inconsistent and is typically at the discretion of the prescriber. Themost common durations of therapy are 7, 10, or 14 days, but courses of 14 days or longer have also been used. Newer data support the use of clinical data to identify resolution of infection, such as defervescence, normalizing white blood cell count, and absence of infiltrate on chest radiograph. Discontinuation of antimicrobials 48 to 72 hours after such clinical resolution may allow for shorter courses of therapy with equivalent efficacy as the more arbitrary end points of 7 to 14 days. The intent of this article is to review the rationale, potential benefit, and relevant studies pertaining to the use of short-course antimicrobial regimens for the treatment of community-acquired and ventilatorassociated pneumonia.
Catheter-Related Bloodstream Infections in the Intensive Care Unit Population
Authors: Haase Krystal K. , McCracken Kari A. , Akins Ronda L.
Published: January 2005

Catheter-related bloodstream infections (CRBIs) are a cause of significant morbidity and mortality in intensive care unit patients. Development of CRBIs may occur by several mechanisms. The role of fibrin and biofilm development and their impact on therapy are described. Multiple preventative strategies related to the insertion and maintenance of the catheter site have been identified. Topical antisepsis and use of antibiotic-impregnated catheters are also beneficial for reducing the incidence of CRBI. Antibiotic lock solutionsmay be effective in preventing CRBI for select patients with longterm catheter use. Treatment of CRBIs should be based on suspected organisms, whichmost commonly include staphylococci, gram-negatives, including Pseudomonas aeruginosa andCandida species. Duration of treatment and decisions regarding catheter removal are controversial. Evaluation and treatment of potential complications of CRBIs, including endocarditis, infected thrombophlebitis, osteomyelitis, and endophthalmitis, are essential.
Conrad in the computer: examples of quantitative stylistic methods
Authors: Stubbs Michael
Published: January 2005

A stylistic analysis of Joseph Conrad’s Heart of Darkness is used to illustrate the literary value of simple quantitative text and corpus data. Cultural and literary aspects of the book are briefly discussed. It is then shown that data on the frequencies and distributions of individual words and recurrent phraseology can not only provide a more detailed descriptive basis for widely accepted literary interpretations of the book, but also identify significant linguistic features which literary critics seem not to have noticed. The argument provides a response to scepticism of quantitative stylistics from both linguists and literary critics.
The poem as complex blend: conceptual mappings of metaphor in Sylvia Plath’s ‘The Applicant’
Authors: Freeman Margaret H.
Published: January 2005

This article aims to show that Fauconnier and Turner’s conceptual integration network or ‘blending’ theory can provide an integrated and coherent account of the cognitive mechanisms by which poetry is constructed and construed. Taking as its example Sylvia Plath’s poem ‘The Applicant’, a poem already analyzed by Elena Semino from the perspectives of discourse, possible worlds, and schema theories, this article shows how Fauconnier and Turner’s optimality constraints interact to provide a complex blending of conceptual metaphors in the poem that reveal the poet’s own conflicted attitudes about marriage and the empty promises of a consumer society just four months before her suicide. Far from providing a new critical reading of the poem, the article makes explicit the implicit mappings that readers adopt in drawing conclusions about the poem that are shared by many literary critics.
From ‘bad’ to ‘worse’: pragmatic scales and the (de)construction of cultural models
Authors: Weber Jean Jacques
Published: January 2005

This article uses a cognitive-pragmatic approach to discourse which is informed by two basic concepts: cultural models and pragmatic scales. The data consist of an essay by a literary writer, Jamaica Kincaid’s A Small Place, as well as editorials and letters to the editor published in a Luxembourgish newspaper. The analysis reveals how the authors of the editorials and letters to the editor both rely upon and construct a particular cultural model about education in Luxembourg, and how the literary writer deconstructs her readers’ (at least potentially stereotypical) model of tourism. Rather than attempt to distinguish between different text genres on such a basis, the article focuses on cognitive aspects that are common to all discourse processing; in particular, it highlights the key role played by pragmatic scales in linking and structuring cultural models. The scales are invoked primarily by evaluative adjective forms such as bad, worse, etc., and they make possible a high degree of linguistic implicitness in the writers’ rhetorical and argumentative strategies. The article concludes that the consequent processes of moving information across evaluative scales and filling in missing values are characteristic of the way human beings think, and that they work together with other processes of reasoning (such as conceptual blending) to produce the full complexity, but also the potentially stereotyped nature, of human thinking.
An experimental examination of the computer’s time displacement effects
Authors: Cai Xiaomei
Published: January 2005

Past research has presented mixed results in regards to the time displacement effects of the computer. In this field experiment, subjects were asked to give up using the computer (except for school work) for one day. The amount of time shift within each traditional medium between the normal day and the non-computer day was examined. The results showed that giving up computer use did not increase time allotted to other media. In addition, no differences in time shifts existed between light and heavy users. Overall, this study provides no support for the claim that using computers takes away time from using traditional media.
A visual convergence of print, television, and the internet: charting 40 years of design change in news presentation
Authors: Cooke Lynne
Published: January 2005

Changes in the visual presentation of news media provide insight into the complex, dynamic relationships that exist between print, television, and the internet. This study explores the longitudinal visual development of five major newspapers, seven network and cable news programs, and twelve news websites by examining the progression of structural and graphic design elements that contribute to the trend of ‘scannable’ information presentation. The analysis is broken down by decade, beginning in 1960 and ending in 2002, and the findings indicate that a visual convergence of media has become more pronounced over the decades as the acceleration of information has increased over time. Implications of this study regarding interdisciplinary research are explored and future research avenues are discussed in the conclusion.
Ekstasis and the internet: liminality and computer-mediated communication
Authors: Waskul Dennis D.
Published: January 2005

Anthropologist Victor Turner suggested that all social worlds are composed of two parallel, yet seemingly contrasting models: society as social structure and society as communitas. The relationships between these two basic elements of human social and cultural life are mediated by ephemeral experiences of liminality. Other major theoretical traditions also recognize these relationships, representing a distinct conceptual framework of direct significance to advancing understandings of the internet. The internet is a natural environment for liminality and ekstasis, a place where self and society must be made to exist in a process where both are translated into the conventions of the medium. Some people actively toy with these representations while others do not. However, in the final analysis these communicative dynamics are rooted in the liminal characteristics of the medium - not the motivations and intents of internet users themselves. Approaching the internet in this way stands in stark contrast to other latent conceptual orientations that are largely concerned with moral dynamics.