bluuebunny/crossref_metadata_2025 huggingface dataset:
2005 Emil Thomas Kaiser Award
Authors: Raines Ronald T.
Published: April 2006

Collagen is the most abundant protein in animals. The conformational stability of the collagen triple helix is enhanced by the hydroxyl group of its prevalent (2S,4R)‐4‐hydroxyproline residues. For 25 years, the prevailing paradigm had been that this enhanced stability is due to hydrogen bonds mediated by bridging water molecules. We tested this hypothesis with synthetic collagen triple helices containing 4‐fluoroproline residues. The results have unveiled a wealth of stereoelectronic effects that contribute markedly to the stability of collagen, as well as other proteins. This new understanding is leading to synthetic collagens for a variety of applications in biotechnology and biomedicine.
Association of a Glu92Lys substitution in MC1R with extended brown in Japanese quail (Coturnix japonica)
Authors: Nadeau N. J. , Minvielle F. , Mundy N. I.
Published: April 2006

We investigated melanocortin 1 receptor (MC1R) as a candidate locus for the Extended brown phenotype in quail, in which there is a general darkening throughout the plumage. An initial screen of variation in MC1R in Extended brown and in wild‐type quails revealed two polymorphic non‐synonymous sites. One of these sites, a G‐to‐A substitution leading to a Glu92Lys mutation, was perfectly associated with plumage phenotype; all Extended brown birds were homozygous for Lys92. Co‐segregation of the Glu92Lys mutation with the Extended brown phenotype was confirmed in 24 progeny of an E/e+ × E/e+ cross. Glu92Lys is likely to be the causative mutation for the increased melanism in Extended brown, given that the same mutation is associated with melanic plumage in many breeds of domestic chicken, as well as in a wild passerine bird (the bananaquit, Coereba flaveola) and laboratory mice. Interestingly, the increase in melanization with the Glu92Lys mutation is less marked in quails than in most other birds and mammals. Phylogenetic results indicate that the Glu92Lys mutation has independently occurred in quail and chicken lineages.
The effect of aprotinin on activated protein C‐mediated downregulation of endogenous thrombin generation
Authors: Tanaka Kenichi A. , Szlam Fania , Levy Jerrold H.
Published: April 2006

Thrombin plays a central role in coagulation and haemostasis. Binding of thrombin to thrombomodulin generates activated protein C (APC), which exerts a negative feedback on thrombin formation. Aprotinin, a natural proteinase inhibitor is used extensively during cardiac surgery because this procedure is often associated with profound activation of coagulation and inflammatory pathways. Some in vitro evidences suggest that aprotinin inhibits APC, but the clinical relevance is unclear. The recombinant human soluble thrombomodulin (rhsTM)‐modified thrombin generation (TG) assay was used to investigate the effects of aprotinin on APC in plasma samples obtained from healthy volunteers, aprotinin‐treated cardiac surgical patients and in protein C (PC)‐depleted plasma. Based on the results of in vitro TG assay, addition of rhsTM (0·75–3·0 μg/ml) to volunteer or patient platelet‐poor plasma significantly reduced (70·8 ± 21·9 and 95·3% ± 4·6%, respectively) thrombin formation when compared with PC‐depleted plasma (8·3% ± 5·2%). Aprotinin (100–200 KIU) caused a small, statistically insignificant decrease in the peak thrombin formation in normal and PC‐deficient plasma (12·0 ± 6·1%). In cardiac surgical patients, levels of functional PC, factor II, antithrombin and platelet significantly decreased after cardiopulmonary bypass (CPB). Soluble thrombomodulin concentrations were increased after CPB (3·5 ± 2·2 to 5·0 ± 2·2 ng/ml), but they were still within the normal range for human plasma. Our results showed that, even though endogenous PC level is decreased after CPB, it retains its activity in the presence of thrombomodulin, and aprotinin has limited inhibitory effect on APC generation.
Intraspecific variation in survival and mitochondrial oxidative phosphorylation in wild‐caught Drosophila simulans
Authors: Melvin Richard G. , Ballard J. William O.
Published: April 2006

Lifespans of organisms vary greatly even among individuals of the same species. Under the framework of the free oxygen radical theory of aging, it is predicted that variation in individual lifespan within a species will correlate with variation in the accumulation of oxidative damage to cell components from reactive oxygen species. In this study we test the hypothesis that variation in survival of three wild‐caught Drosophila simulans fly lines (HW09, NC48 and MD106) correlates with three key aspects of mitochondrial bioenergetics. The rank order of median survival was HW09 > MD106 > NC48. Young HW09 flies (11–18 days) had (i) highest ADP:O (quantity of oxygen consumed by mitochondria when provided with a quantity of ADP) when metabolizing both electron transport chain complex I and complex III substrates; (ii) lowest rate of mitochondrial hydrogen peroxide production from complex III; and (iii) highest cytochrome c oxidase activity from complex IV. Rate of hydrogen peroxide production increased and cytochrome c oxidase activity decreased in all lines in the age range 11–25 days. This is the first study to correlate natural variation in organism survival with natural variation in mitochondrial bioenergetics.
Clinicopathological and prognostic characteristics of CD33‐positive multiple myeloma
Authors: Sahara Naohi , Ohnishi Kazunori , Ono Takaaki , Sugimoto Yuya , Kobayashi Miki , Takeshita Kaori , Shigeno Kazuyuki , Nakamura Satoki , Naito Kensuke , Tamashima Sadahiro , Nara Kenji , Tobita Tadasu , Takeshita Akihiro , Ohno Ryuzo
Published: April 2006

Abstract:  There have been few reports about the CD33 expression on multiple myeloma (MM) cells so far, showing that only a few patients expressed CD33 homogenously on their MM cells. However, in these reports, neither detailed clinical information nor its prognostic significance was described. Therefore, we analyzed the CD33 expression on MM cells from 63 newly diagnosed patients by flow cytometry and the correlation with other clinical parameters to determine the clinicopathological significance of this molecule. Fourteen (22%) patients were positive for CD33. Of the 14 patients with CD33+ MM, >80% of MM cells were positive in six (9.5%). The CD33+ patients had higher β2 microglobulin and lactate dehydrogenase levels and higher incidence of anemia and thrombocytopenia than did CD33− patients. The estimated 3‐yr overall survival in CD33+ patients was significantly lower than in the CD33− ones (31% and 50%, respectively, P = 0.042). Especially, mortality within a year from diagnosis in the CD33+patients was higher than that in CD33− patients (43% and 10%, respectively, P = 0.005). Serial evaluation of CD33 expression showed that the amount of CD33 significantly increased after a variety of treatment including melphalan and steroid in individual patients. These results suggest that the CD33 expression might be associated with drug resistance to these conventional agents, and CD33 might be a useful target for the development of new therapeutic agents in MM.
Differentiation of hematopoietic progenitor cells towards the myeloid and B‐lymphoid lineage by hepatocyte growth factor (HGF) and thrombopoietin (TPO) together with early acting cytokines
Authors: Grassinger Jochen , Mueller Gunnar , Zaiss Matthias , Kunz‐Schughart Leoni A. , Andreesen Reinhard , Hennemann Burkhard
Published: April 2006

Abstract:  Objectives: The effect of stem cell factor (SCF), flt3‐ligand (FL), and interleukin (IL)‐3 (SF3) in combination with hepatocyte growth factor (HGF), thrombopoietin (TPO), and Hyper‐IL‐6 on maintenance and differentiation of early human peripheral blood‐derived progenitor cells was investigated. Methods: Single sorted CD34+ 38− cells were cultured with various combinations of these growth factors in order to identify the most effective cytokine combination. Then, lineage‐depleted cells were stimulated for 7 d in bulk culture before they were assessed by flow cytometry and in functional assays. Results: The highest number of clones in the single‐cell assay was obtained after culture with SF3 + TPO + HGF. Cell expansion with SF3 + TPO + HGF yielded an increase of the total cell number (11‐fold), the number of CD34+ cells (sevenfold), colony forming cells (CFC; 13‐fold), granulocytes (CD15/66b+; 45‐fold) and B‐cells (CD19/20+; 55‐fold). However, the number of long‐term culture initiating cells (LTC‐IC) decreased from 779 ± 338 per 1 × 105 CD34+ cells on day 0 to 253 ± 115 on day 7. In parallel, the number of pluripotent mouse repopulating cells decreased by the factor 11, and no significant change in the proportion of human myeloid or lymphoid cells found in the mouse bone marrow was noted. Conclusion: The observation that mature cells of different lineages are generated and that transplantable multipotent hematopoietic cells are lost during culture suggests the differentiation of early hematopoietic progenitors toward lineage committed cells by the tested cytokines. The detection of cells expressing B‐lymphoid markers after culture indicates a possible role in the propagation of B‐cells.
Genes and neurons: molecular insights to fear and anxiety
Authors: Stoppel C. , Albrecht A. , Pape H.‐C. , Stork O.
Published: April 2006

Experimental animal models provide an important tool for the identification of inheritable components of fear and anxiety. ‘Pavlovian’ fear conditioning has been tremendously successful to characterize the neuronal circuitry and cellular mechanisms of the formation, consolidation and extinction of fear memories. Here we summarize recent progress that has led to the identification of gene products contributing to such experience‐dependent changes in fear and anxiety and may guide the search for genetic factors involved in the development and treatment of human anxiety disorders.
Mitogen‐activated protein kinase/extracellular regulated kinase signalling and memory stabilization: a review
Authors: Davis Sabrina , Laroche Serge
Published: April 2006

The function of mitogen‐activated protein kinase (MAPK) in neurons has been the subject of considerable scrunity of late, and recent studies have given new insights into how this signalling cascade can regulate gene expression following cell‐surface receptor activation. At the same time, a wealth of experimental data has demonstrated that the MAPK cascade is critically involved in the mechanisms underlying the type of enduring modification of neural networks required for the stability of memories, emphasizing the high level of interest in this signalling molecule. In this review, we briefly outline the main molecular events and mechanisms of the regulation of the MAPK cascade leading to transcriptional activation and summarize recent advances in our understanding of the functional role of this molecular signalling cascade in regulating brain plasticity, memory consolidation and memory reconsolidation.
Interplay of Efflux System,
ampC
, and
oprD
Expression in Carbapenem Resistance of
Pseudomonas aeruginosa
Clinical Isolates
Authors: Quale John , Bratu Simona , Gupta Jyoti , Landman David
Published: April 2006

Carbapenems are important agents for the therapy of infections due to multidrug-resistant
Pseudomonas aeruginosa
; the development of carbapenem resistance hampers effective therapeutic options. To assess the mechanisms leading to resistance, 33 clinical isolates with differing degrees of carbapenem susceptibility were analyzed for the expression of the chromosomal β-lactamase (
ampC
), the porin that is important for the entry of carbapenems (
oprD
), and the proteins involved in four efflux systems (
mexA
,
mexC
,
mexE
, and
mexX
). Real-time reverse transcriptase PCR was performed using primers and fluorescent probes for each of the target genes. The sequencing of regulatory genes (
ampR
,
mexR
,
nalC
,
nalD
,
mexT
, and
mexZ
) was also performed. Diminished expression of
oprD
was present in all imipenem- and meropenem-resistant isolates but was not required for ertapenem resistance. Increased expression of
ampC
was not observed in several isolates that were overtly resistant to carbapenems. Increased expression of several efflux systems was observed in many of the carbapenem-resistant isolates. Increased efflux activity correlated with high-level ertapenem resistance and reduced susceptibility to meropenem and aztreonam. Most isolates with increased expression of
mexA
had mutations affecting
nalC
and/or
nalD
. Two isolates with mutations leading to a premature stop codon in
mexZ
had markedly elevated
mexX
expressions, although mutations in
mexZ
were not a prerequisite for overexpression. β-Lactam resistance in clinical isolates of
P. aeruginosa
is a result of the interplay between diminished production of
oprD
, increased activity of
ampC
, and several efflux systems.
Calcium Signals Are Affected by Ciprofloxacin as a Consequence of Reduction of Mitochondrial DNA Content in Jurkat Cells
Authors: Kozieł Rafał , Zabłocki Krzysztof , Duszyński Jerzy
Published: April 2006

The effects of ciprofloxacin on mitochondrial DNA (mtDNA) content, oxygen consumption, mitochondrial membrane potential, cellular ATP formation, and capacitative Ca
2+
entry into Jurkat cells were investigated. In cells incubated for several days with 25 μg/ml ciprofloxacin, a 60% reduction of mtDNA content, inhibition of the respiratory chain, and a significant decrease in mitochondrial membrane potential were observed. These changes led to a decrease in the calcium buffering capacity of mitochondria which, in turn, resulted in a gradual inhibition of the capacitative Ca
2+
entry. On days 4, 7, and 11 of incubation with ciprofloxacin, the initial rates of Ca
2+
entry were reduced by 33%, 50%, and 50%, respectively. Ciprofloxacin caused a transient decrease in the cellular capability for ATP formation. In cells incubated for 15 min with glucose, pyruvate, and glutamine as exogenous fuel, ciprofloxacin reduced ATP content by 16% and 35% on days 4 and 7, respectively, of incubation with the drug. However, on day 11 of incubation with ciprofloxacin, a recovery of cellular ATP formation was observed. In conclusion, long-term exposure of Jurkat cells to ciprofloxacin at a concentration of 25 μg/ml seriously affects cellular energy metabolism and calcium homeostasis.
Extended-Spectrum β-Lactamases and Plasmid-Mediated AmpC Enzymes among Clinical Isolates of
Escherichia coli
and
Klebsiella pneumoniae
from Seven Medical Centers in Taiwan
Authors: Yan Jing-Jou , Hsueh Po-Ren , Lu Jang-Jih , Chang Feng-Yee , Shyr Jainn-Ming , Wan Jen-Hsien , Liu Yung-Ching , Chuang Yin-Ching , Yang Yi-Chueh , Tsao Shih-Ming , Wu Hsiu-Hung , Wang Li-Shin , Lin Tsuey-Pin , Wu Hsiu-Mei , Chen Hung-Mo , Wu Jiunn-Jong
Published: April 2006

Production of extended-spectrum β-lactamases and plasmid-mediated AmpC enzymes was investigated among 291
Escherichia coli
and 282
Klebsiella pneumoniae
isolates that showed decreased susceptibilities to extended-spectrum cephalosporins from seven Taiwanese medical centers. CTX-M-type and SHV-type enzymes were the most prevalent extended-spectrum β-lactamases. CMY-2-like and DHA-1-like β-lactamases were the most prevalent AmpC-type enzymes.
Neuraminidase Inhibitor-Resistant and -Sensitive Influenza B Viruses Isolated from an Untreated Human Patient
Authors: Hurt Aeron C. , Iannello Pina , Jachno Kim , Komadina Naomi , Hampson Alan W. , Barr Ian G. , McKimm-Breschkin Jennifer L.
Published: April 2006

An influenza B virus from an infant with no history of treatment or contact with neuraminidase inhibitors demonstrated a significant reduction in sensitivity to these drugs. Here, we describe the analysis of a mixed viral population that contained a novel D197E amino acid substitution that was responsible for this reduction.
Effects of Mutations in the Human Immunodeficiency Virus Type 1
gag
Gene on RNA Packaging and Recombination
Authors: Nikolaitchik Olga , Rhodes Terence D. , Ott David , Hu Wei-Shau
Published: April 2006

Human immunodeficiency virus type 1 (HIV-1) recombination occurs during reverse transcription when parts of the two copackaged RNAs are used as templates for DNA synthesis. It was previously hypothesized that HIV-1 Gag polyproteins preferentially encapsidate the RNA from which they were translated (
cis
-packaging hypothesis). This hypothesis implies that mutants encoding Gag that cannot efficiently package viral RNA are selected against at two levels: these mutants do not generate infectious virus, and these mutants are not efficiently rescued by the wild-type virus because the mutant RNAs are packaged at much lower levels than are those of the wild-type genome. Therefore, genetic information encoded by
gag
mutants can be rapidly lost in the viral population. To test this prediction of the
cis
-packaging hypothesis, we examined several
gag
mutants by measuring the efficiencies of the mutant RNAs in being packaged in
trans
in the presence of wild-type virus and determining the rates of recombination between
gag
mutants and wild-type viruses. We observed that the viral RNAs from the nucleocapsid zinc finger or the capsid truncation mutant were packaged efficiently in
trans
, and these mutant viruses also frequently recombined with the wild-type viruses. In contrast, viral RNAs from mutants containing a 6-nucleotide substitution encompassing the
gag
AUG were not efficiently encapsidated, resulting in a low rate of recombination between the mutants and wild-type viruses. Further analyses revealed that other, more subtle mutations changing the
gag
AUG and abolishing Gag translation did not interfere with efficient encapsidation of the mutant RNA. Our results indicated that neither the
gag
AUG sequence nor Gag translation is essential for viral RNA encapsidation, and Gag can package both wild-type and
gag
mutant RNAs with similar efficiencies. Therefore, we propose that HIV-1 RNA encapsidation occurs mainly in
trans
, and most
gag
mutants can be rescued by wild-type virus; therefore, they are unlikely to face the aforementioned double-negative selection.
A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences
Authors: Jensen Mark A. , Coetzer Mia , van 't Wout Angélique B. , Morris Lynn , Mullins James I.
Published: April 2006

In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5
+
and 51 SI CXCR4
+
sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.
African Swine Fever Virus Protein pE296R Is a DNA Repair Apurinic/Apyrimidinic Endonuclease Required for Virus Growth in Swine Macrophages
Authors: Redrejo-Rodríguez Modesto , García-Escudero Ramón , Yáñez-Muñoz Rafael J. , Salas María L. , Salas José
Published: April 2006

We show here that the African swine fever virus (ASFV) protein pE296R, predicted to be a class II apurinic/apyrimidinic (AP) endonuclease, possesses endonucleolytic activity specific for AP sites. Biochemical characterization of the purified recombinant enzyme indicated that the

K
m

and catalytic efficiency values for the endonucleolytic reaction are in the range of those reported for
Escherichia coli
endonuclease IV (endo IV) and human Ape1. In addition to endonuclease activity, the ASFV enzyme has a proofreading 3′→5′ exonuclease activity that is considerably more efficient in the elimination of a mismatch than in that of a correctly paired base. The three-dimensional structure predicted for the pE296R protein underscores the structural similarities between endo IV and the viral protein, supporting a common mechanism for the cleavage reaction. During infection, the protein is expressed at early times and accumulates at later times. The early enzyme is localized in the nucleus and the cytoplasm, while the late protein is found only in the cytoplasm. ASFV carries two other proteins, DNA polymerase X and ligase, that, together with the viral AP endonuclease, could act as a viral base excision repair system to protect the virus genome in the highly oxidative environment of the swine macrophage, the virus host cell. Using an ASFV deletion mutant lacking the E296R gene, we have determined that the viral endonuclease is required for virus growth in macrophages but not in Vero cells. This finding supports the existence of a viral reparative system to maintain virus viability in the infected macrophage.
The High-Frequency Major Histocompatibility Complex Class I Allele
Mamu-B

*

17
Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication
Authors: Yant Levi J. , Friedrich Thomas C. , Johnson Randall C. , May Gemma E. , Maness Nicholas J. , Enz Alissa M. , Lifson Jeffrey D. , O'Connor David H. , Carrington Mary , Watkins David I.
Published: April 2006

Particular HLA alleles are associated with reduced human immunodeficiency virus replication. It has been difficult, however, to characterize the immune correlates of viral control. An analysis of the influence of major histocompatibility complex class I alleles on viral control in 181 simian immunodeficiency virus SIVmac239-infected rhesus macaques revealed that
Mamu-B

*

17
was associated with a 26-fold reduction in plasma virus concentrations (
P
< 0.001).
Mamu-B

*

17
was also enriched 1,000-fold in a group of animals that controlled viral replication. Even after accounting for this group,
Mamu-B

*

17
was associated with an eightfold reduction in plasma virus concentrations (
P
< 0.001).
Mamu-B

*

17-
positive macaques could, therefore, facilitate our understanding of the correlates of viral control.
NEW PREDICTIONS OF GENERALIZED SPIN POLARIZABILITIES IN HEAVY BARYON CHIRAL PERTURBATION THEORY
Authors: KAO CHUNG-WEN
Published: April 2006

We review the recent progress of the theoretical understanding of the spin structure of the nucleon based on Heavy Baryon Chiral Perturbation Theory (HBChPT). At low Q2 the spin structure of the nucleon is encoded into the generalized spin polarizabilities (spin GP's) extracted from the virtual Compton scattering (VCS) amplitudes. The spin GP's of the nucleon have been calculated up to next-to-leading order in HBChPT. Furthermore, the forward spin generalized polarizabilities, which are related to the nucleon polarized structure functions g1 and g2 through the sum rules based on dispersion relations, also have been calculated in HBChPT up to next-to-leading order. As a summary, the physics content of the existing data is discussed and some perspectives for future theoretical and experimental activities in this field are also presented.
A SHORT COMMENT ON THE JUPITER TIME-DELAY CONTROVERSIES
Authors: CARLIP S.
Published: April 2006

The observation of Shapiro time delay of quasar light passing near Jupiter1 generated considerable excitement, but also considerable controversy. The disagreements involve two distinct issues: (i) Is there a vJ/c term in the time delay that is large enough to detect? (ii) If so, is the factor of c in the delay the "speed of gravity" cg or the "speed of light" c? I will comment briefly on each.
Firing Patterns of Accumbal Neurons During a Pavlovian-Conditioned Approach Task
Authors: Wan Xun , Peoples Laura L.
Published: April 2006

The nucleus accumbens (NAc) is necessary for the expression of Pavlovian-conditioned approach behavior but not for the expression of instrumental behavior conditioned in sessions that set a low response requirement. Although numerous studies have characterized firing patterns of NAc neurons in relation to instrumental behavior, very little is known about how NAc neurons encode information in Pavlovian tasks. In the present study, recordings of accumbal firing patterns were made during sessions in which rats performed a Pavlovian-conditioned approach task. Most of the recorded neurons (74/83, 89%) exhibited significant responses during the conditioned stimulus (CS) presentation and/or the reward exposure. The reward responses were prevalent, predominantly inhibitory, and comparable to reward responses observed in various types of behavioral paradigms, including instrumental tasks. The CS responses could be segregated into multiple subtypes on the basis of directionality, onset latency, and duration. Several characteristics of the CS firing patterns were unique relative to cue responses observed previously during alternative types of conditioning sessions. It is possible that the novel firing patterns correspond to the differential contributions of the accumbens to Pavlovian-conditioned approach behavior and instrumentally conditioned behavior. Regardless, the novel patterns of firing add to existing evidence that characterization of accumbal firing patterns in Pavlovian tasks may provide additional information about the neurophysiological mechanisms that mediate accumbal contributions to behavior.
Iron-related transcriptomic variations in CaCo-2 cells, an in vitro model of intestinal absorptive cells
Authors: Chicault Céline , Toutain Bertrand , Monnier Annabelle , Aubry Marc , Fergelot Patricia , Treut Andre Le , Galibert Marie-Dominique , Mosser Jean
Published: April 2006

Regulation of iron absorption by duodenal enterocytes is essential for the maintenance of homeostasis by preventing iron deficiency or overload. Despite the identification of a number of genes implicated in iron absorption and its regulation, it is likely that further factors remain to be identified. For that purpose, we used a global transcriptomic approach, using the CaCo-2 cell line as an in vitro model of intestinal absorptive cells. Pangenomic screening for variations in gene expression correlating with intracellular iron content allowed us to identify 171 genes. One hundred nine of these genes are clustered into five types of expression profile. This is the first time that most of these genes have been associated with iron metabolism. Functional annotation of these five clusters indicates potential links between the immune response, proteolysis processes, and iron depletion. In contrast, iron overload is associated with cellular metabolism, especially that of lipids and glutathione involving redox function and electron transfer.
Rainfall Climate Regimes: The Relationship of Regional TRMM Rainfall Biases to the Environment
Authors: Berg Wesley , L'Ecuyer Tristan , Kummerow Christian
Published: April 2006

Intercomparisons of satellite rainfall products have historically focused on the issue of global mean biases. Regional and temporal variations in these biases, however, are equally important for many climate applications. This has led to a critical examination of rainfall estimates from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and precipitation radar (PR). Because of the time-dependent nature of these biases, it is not possible to apply corrections based on regionally defined characteristics. Instead, this paper seeks to relate PR–TMI differences to physical variables that can lead to a better understanding of the mechanisms responsible for the observed differences. To simplify the analysis, issues related to differences in rainfall detection and intensity are investigated separately. For clouds identified as raining by both sensors, differences in rainfall intensity are found to be highly correlated with column water vapor. Adjusting either TMI or PR rain rates based on this simple relationship, which is relatively invariant over both seasonal and interannual time scales, results in a 65%–75% reduction in the rms difference between seasonally averaged climate rainfall estimates. Differences in rainfall detection are most prominent along the midlatitude storm tracks, where widespread, isolated convection trailing frontal systems is often detected only by the higher-resolution PR. Conversely, over the East China Sea clouds below the ∼18-dBZ PR rainfall detection threshold are frequently identified as raining by the TMI. Calculations based on in situ aerosol data collected south of Japan support a hypothesis that high concentrations of sulfate aerosols may contribute to abnormally high liquid water contents within nonprecipitating clouds in this region.
North Atlantic Subtropical Mode Waters and Ocean Memory in HadCM3
Authors: Old Chris , Haines Keith
Published: April 2006

A study of the formation and propagation of volume anomalies in North Atlantic Mode Waters is presented, based on 100 yr of monthly mean fields taken from the control run of the Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3). Analysis of the temporal and spatial variability in the thickness between pairs of isothermal surfaces bounding the central temperature of the three main North Atlantic subtropical mode waters shows that large-scale variability in formation occurs over time scales ranging from 5 to 20 yr. The largest formation anomalies are associated with a southward shift in the mixed layer isothermal distribution, possibly due to changes in the gyre dynamics and/or changes in the overlying wind field and air–sea heat fluxes. The persistence of these anomalies is shown to result from their subduction beneath the winter mixed layer base where they recirculate around the subtropical gyre in the background geostrophic flow. Anomalies in the warmest mode (18°C) formed on the western side of the basin persist for up to 5 yr. They are removed by mixing transformation to warmer classes and are returned to the seasonal mixed layer near the Gulf Stream where the stored heat may be released to the atmosphere. Anomalies in the cooler modes (16° and 14°C) formed on the eastern side of the basin persist for up to 10 yr. There is no clear evidence of significant transformation of these cooler mode anomalies to adjacent classes. It has been proposed that the eastern anomalies are removed through a tropical–subtropical water mass exchange mechanism beneath the trade wind belt (south of 20°N). The analysis shows that anomalous mode water formation plays a key role in the long-term storage of heat in the model, and that the release of heat associated with these anomalies suggests a predictable climate feedback mechanism.
Redesigning Hospital Gowns to Enhance End Users' Satisfaction
Authors: Cho KyeongSook
Published: April 2006

The design considerations for hospital gowns were investigated through a review of previous research and interviews with licensed practical nurses and patients who had been hospitalized and wore hospital gowns during their hospitalization. Two designs of prototype hospital gowns, Prototypes A and B, were proposed and users' comfort perceptions per prototype were compared to a conventional gown to evaluate their satisfaction through wear trials with 12 female participants. Prototype A featured a front opening and a back‐slit overlap. Prototype B was composed of openings on the upper chest area and on the side and cap sleeves. Back opening with ties and raglan sleeves were the main features of the conventional gowns. Prototype A was more acceptable to the participants than the conventional gown. On the basis of the findings of this study, guidelines are provided for a hospital gown design to enhance the users' satisfaction.
Sustainable Highways
Authors: Bartle John R. , Devan Jijesh
Published: April 2006

Highway travel is forecasted to increase steadily worldwide in the foreseeable future. However, this pattern is unsustainable environmentally, economically, financially, and socially. Federal legislation, in particular the Intermodal Surface Transportation Efficiency Act, has made progress toward the goal of sustainability, and technological improvements offer potential for reduced emissions, but both potentials have not been fully realized. Reduced use and redesigned taxes are unlikely possibilities. Ultimately, institutions will have to change. The European Union offers an example of how the institutional change can be implemented in a durable way. This change is important not just for environmental reasons but also for long-term prosperity.
Correction of a murine model of von Willebrand disease by gene transfer
Authors: Pergolizzi Robert G. , Jin Guangchun , Chan Diane , Pierre Lorraine , Bussel James , Ferris Barbara , Leopold Philip L. , Crystal Ronald G.
Published: April 2006

von Willebrand disease (VWD), the most common inherited bleeding disorder in the U.S. population, is caused by defects in the expression and processing of von Willebrand factor (VWF), a blood glycoprotein required for normal hemostasis that mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet glycoproteins and to constituents of exposed connective tissue. To assess whether VWF deficiency can be corrected by gene transfer, a plasmid expressing the intact 8.4-kb murine VWF coding sequence, directed by the cyto-megalovirus immediate/early promoter/enhancer, was delivered through hydrodynamic tail vein injection into VWF knockout mice (VWF–/–) that exhibit defects in hemostasis, including highly prolonged bleeding time and spontaneous bleeding events, closely mimicking severe human VWD. VWF antigen levels in plasma from animals receiving VWF cDNA, but not control animals, revealed normalized levels of circulating VWF that persisted for at least 1 week after injection. Western blot analysis of plasma from animals receiving VWF cDNA, but not control animals, revealed high molecular–weight multimers with patterns similar to those observed in wild-type mice. Reverse transcription–polymerase chain reaction (RT-PCR) on RNA isolated from the livers of animals receiving VWF cDNA, but not control animals, demonstrated that VWF was expressed in the liver, and immunohistochemical analysis of the livers of treated VWF–/– mice revealed VWF-specific staining throughout the liver parenchyma but not in endothelial cells. Plasma from treated VWF–/– mice, but not control VWF–/– mice, supported the hypothesis that murine platelets aggregate in the presence of botrocetin. Although levels of circulating factor VIII in untreated VWF–/– mice were less than 10% those in wild-type mice, levels of factor VIII in VWF–/– animals treated with VWF cDNA, but not in control animals, were normalized to values in wild-type mice, indicating the restoration of factor VIII carrier function for VWF in treated mice that persisted for at least 1 week at higher doses of VWF cDNA. Most important, bleeding time was normalized by 48 hours after the delivery of VWF cDNA, but not by the control plasmid. These data suggest that with the use of gene transfer of VWF cDNA, VWF protein can be expressed, processed, and secreted in a physiologically active form; thus, it may be possible to correct VWD using gene transfer.
VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment
Authors: Gampel Alexandra , Moss Lara , Jones Matt C. , Brunton Val , Norman Jim C. , Mellor Harry
Published: April 2006

Endothelial cells respond to vascular endothelial growth factor (VEGF) to produce new blood vessels. This process of angiogenesis makes a critical contribution during embryogenesis and also in the response to ischemia in adult tissues. We have studied the intracellular trafficking of the major VEGF receptor KDR (VEGFR2). Unlike other related growth factor receptors, we find that a significant proportion of KDR is held in an endosomal storage pool within endothelial cells. We find that KDR can be delivered to the plasma membrane from this intracellular pool and that VEGF stimulates this recycling to the cell surface. KDR recycling appears to be distinct from the previously characterized Rab4- and Rab11-dependent pathways, but, instead, KDR+ recycling vesicles contain Src tyrosine kinase and VEGF-stimulated recycling requires Src activation. Taken together, these data show that intracellular trafficking of KDR is markedly different from other receptor tyrosine kinases and suggest that the regulation of KDR trafficking by VEGF provides a novel mechanism for controlling the sensitivity of endothelial cells to proangiogenic signals.
Support vector machine for classification of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae based on codon composition
Authors: Zhou Tong , Weng Jianhong , Sun Xiao , Lu Zuhong
Published: April 2006

Background

Meiotic double-strand breaks occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). Hotspots and coldspots are receiving increasing attention in research into the mechanism of meiotic recombination. However, predicting hotspots and coldspots from DNA sequence information is still a challenging task.

Results

We present a novel method for classification of hot and cold ORFs located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using support vector machine (SVM), which relies on codon composition differences. This method has achieved a high classification accuracy of 85.0%. Since codon composition is a fusion of codon usage bias and amino acid composition signals, the ability of these two kinds of sequence attributes to discriminate hot ORFs from cold ORFs was also investigated separately. Our results indicate that neither codon usage bias nor amino acid composition taken separately performed as well as codon composition. Moreover, our SVM based method was applied to the full genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of recombination rate. We found that the performance of our method for predicting cold ORFs is not as good as that for predicting hot ORFs. Besides, we also observed a considerable correlation between meiotic recombination rate and amino acid composition of certain residues, which probably reflects the structural and functional dissimilarity between the hot and cold groups.

Conclusion

We have introduced a SVM-based novel method to discriminate hot ORFs from cold ones. Applying codon composition as sequence attributes, we have achieved a high classification accuracy, which suggests that codon composition has strong potential to be used as sequence attributes in the prediction of hot and cold ORFs.
IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(D)J recombinations
Authors: Baum Thierry-Pascal , Hierle Vivien , Pasqual Nicolas , Bellahcene Fatena , Chaume Denys , Lefranc Marie-Paule , Jouvin-Marche Evelyne , Marche Patrice Noël , Demongeot Jacques
Published: April 2006

Background

Adaptative immune repertoire diversity in vertebrate species is generated by recombination of variable (V), diversity (D) and joining (J) genes in the immunoglobulin (IG) loci of B lymphocytes and in the T cell receptor (TR) loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level involve recombination signal sequences (RSS). Whereas many data exist, they are scattered in non specialized resources with different nomenclatures (eg. flat files) and are difficult to extract.

Description

IMGT/GeneInfo is an online information system that provides, through a user-friendly interface, exhaustive information resulting from the complex mechanisms of T cell receptor V-J and V-D-J recombinations. T cells comprise two populations which express the αβ and γδ TR, respectively. The first version of the system dealt with theHomo sapiensandMus musculusTRA and TRB loci whose gene rearrangements allow the synthesis of the αβ TR chains. In this paper, we present the second version of IMGT/GeneInfo where we complete the database for theHomo sapiensandMus musculusTRG and TRD loci along with the introduction of a quality control procedure for existing and new data. We also include new functionalities to the four loci analysis, giving, to date, a very informative tool which allows to work on V(D)J genes of all TR loci in both human and mouse species. IMGT/GeneInfo provides more than 59,000 rearrangement combinations with a full gene description which is freely available athttp://imgt.cines.fr/GeneInfo.

Conclusion

IMGT/GeneInfo allows all TR information sequences to be in the same spot, and are now available within two computer-mouse clicks. This is useful for biologists and bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and their applications in immune response analysis.
The complete chloroplast genome sequence of the chlorophycean green alga Scenedesmus obliquus reveals a compact gene organization and a biased distribution of genes on the two DNA strands
Authors: de Cambiaire Jean-Charles , Otis Christian , Lemieux Claude , Turmel Monique
Published: April 2006

Background

The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. While the basal position of the Prasinophyceae is well established, the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae (UTC) remains uncertain. The five complete chloroplast DNA (cpDNA) sequences currently available for representatives of these classes display considerable variability in overall structure, gene content, gene density, intron content and gene order. Among these genomes, that of the chlorophycean green alga Chlamydomonas reinhardtii has retained the least ancestral features. The two single-copy regions, which are separated from one another by the large inverted repeat (IR), have similar sizes, rather than unequal sizes, and differ radically in both gene contents and gene organizations relative to the single-copy regions of prasinophyte and ulvophyte cpDNAs. To gain insights into the various changes that underwent the chloroplast genome during the evolution of chlorophycean green algae, we have sequenced the cpDNA of Scenedesmus obliquus, a member of a distinct chlorophycean lineage.

Results

The 161,452 bp IR-containing genome of Scenedesmus features single-copy regions of similar sizes, encodes 96 genes, i.e. only two additional genes (infA and rpl12) relative to its Chlamydomonas homologue and contains seven group I and two group II introns. It is clearly more compact than the four UTC algal cpDNAs that have been examined so far, displays the lowest proportion of short repeats among these algae and shows a stronger bias in clustering of genes on the same DNA strand compared to Chlamydomonas cpDNA. Like the latter genome, Scenedesmus cpDNA displays only a few ancestral gene clusters. The two chlorophycean genomes share 11 gene clusters that are not found in previously sequenced trebouxiophyte and ulvophyte cpDNAs as well as a few genes that have an unusual structure; however, their single-copy regions differ considerably in gene content.

Conclusion

Our results underscore the remarkable plasticity of the chlorophycean chloroplast genome. Owing to this plasticity, only a sketchy portrait could be drawn for the chloroplast genome of the last common ancestor of Scenedesmus and Chlamydomonas.
Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues
Authors: Aouacheria Abdel , Navratil Vincent , Barthelaix Audrey , Mouchiroud Dominique , Gautier Christian
Published: April 2006

Background

Owing to the explosion of information generated by human genomics, analysis of publicly available databases can help identify potential candidate genes relevant to the cancerous phenotype. The aim of this study was to scan for such genes by whole-genome in silico subtraction using Expressed Sequence Tag (EST) data.

Methods

Genes differentially expressed in normal versus tumor tissues were identified using a computer-based differential display strategy. Bcl-xL, an anti-apoptotic member of the Bcl-2 family, was selected for confirmation by western blot analysis.

Results

Our genome-wide expression analysis identified a set of genes whose differential expression may be attributed to the genetic alterations associated with tumor formation and malignant growth. We propose complete lists of genes that may serve as targets for projects seeking novel candidates for cancer diagnosis and therapy. Our validation result showed increased protein levels of Bcl-xL in two different liver cancer specimens compared to normal liver. Notably, our EST-based data mining procedure indicated that most of the changes in gene expression observed in cancer cells corresponded to gene inactivation patterns. Chromosomes and chromosomal regions most frequently associated with aberrant expression changes in cancer libraries were also determined.

Conclusion

Through the description of several candidates (including genes encoding extracellular matrix and ribosomal components, cytoskeletal proteins, apoptotic regulators, and novel tissue-specific biomarkers), our study illustrates the utility of in silico transcriptomics to identify tumor cell signatures, tumor-related genes and chromosomal regions frequently associated with aberrant expression in cancer.
Does population screening for Chlamydia trachomatisraise anxiety among those tested? Findings from a population based chlamydia screening study
Authors: Campbell Rona , Mills Nicola , Sanford Emma , Graham Anna , Low Nicola , Peters Tim J ,   the Chlamydia Screening Studies (ClaSS) Group
Published: April 2006

Background

The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection, which is now the most common in the United Kingdom. The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety, depression and self-esteem.

Methods

19,773 men and women aged 16 to 39 years, selected at random from 27 general practices in two large city areas (Bristol and Birmingham) were invited by post to send home-collected urine samples or vulvo-vaginal swabs for chlamydia testing. Questionnaires enquiring about anxiety, depression and self-esteem were sent to random samples of those offered screening: one month before the dispatch of invitations; when participants returned samples; and after receiving a negative result.

Results

Home screening was associated with an overall reduction in anxiety scores. An invitation to participate did not increase anxiety levels. Anxiety scores in men were lower after receiving the invitation than at baseline. Amongst women anxiety was reduced after receipt of negative test results. Neither depression nor self-esteem scores were affected by screening.

Conclusion

Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents. There is, however, a clear difference between men and women in when this reduction occurs.