bluuebunny/crossref_metadata_2025 huggingface dataset:
The Linear Stability Analysis of the Lamb–Oseen Vortex in a Finite-Length Pipe
Authors: Wang S. , Taylor S. , Akil K. Ku
Published: March 2010

This article extends the perturbation method introduced by Wang (2008, “A Novel Method for Analyzing the Global Stability of Inviscid Columnar Swirling Flow in a Finite Pipe,” Phys. Fluids, 20(7), p. 074101) to determine the global stability of a swirling flow in a straight circular pipe with specified inlet and outlet boundary conditions. To accurately compute the flow stability characteristics, a general procedure to treat the complexity arising from high-order terms is developed. It extends the previous fourth-order method to an eighth-order method. The technique is first applied to the benchmark case of a solid-body rotation flow with a uniform axial speed. It is demonstrated that the eighth-order method is sufficient to construct the growth rate curve between the first and second critical swirls of this flow. Note that this range of swirl is crucial for the study of the vortex breakdown phenomenon since the base flow is unstable and starts the initial stage of transition to a breakdown state. The method is then applied to the Lamb–Oseen vortex to construct the growth rate curve between the first and second critical swirls of this flow. Calculated results are compared with the growth rate curve computed from direct numerical simulations and an overall agreement between the two computations is found. This demonstrates that the Wang and Rusak (1996, “On the Stability of an Axisymmetric Rotating Flow in a Pipe,” Phys. Fluids, 8(4), pp. 1007–1076) instability mechanism captures quantitatively the initial growth of disturbance, which eventually evolves into a breakdown state.
A Critical Role for α4βδ GABA
A
Receptors in Shaping Learning Deficits at Puberty in Mice
Authors: Shen Hui , Sabaliauskas Nicole , Sherpa Ang , Fenton André A. , Stelzer Armin , Aoki Chiye , Smith Sheryl S.
Published: March 2010

Puberty Impairs Plasticity

While the existence of a period of reduced learning coinciding with the onset of puberty in mice is well characterized, the underlying cellular and molecular mechanisms remain unclear.

Shen
et al.

(p.
1515
) assessed the role of specific γ-aminobutyric acid type A (GABA
A
) receptors for restricting hippocampal plasticity during puberty. At puberty, but not in adults or the very young, GABA receptors containing the α4 and δ subunits were targeted perisynaptically to excitatory synapses, shunting the depolarizing current necessary for
N
-methyl-
d
-aspartate (NMDA) receptor activation. As a consequence, signal transmission was affected and spatial learning reduced.
Seminal Fluid Mediates Ejaculate Competition in Social Insects
Authors: den Boer Susanne P. A. , Baer Boris , Boomsma Jacobus J.
Published: March 2010

Sperm Wars

Some female insects mate on only one day of their life, but then they may mate with multiple males and store the sperm, sometimes for years. But as the mates compete for mates, so their sperm compete for ova, and competition between ejaculates can result in the destruction of sperm inside multiply mated females. But females need to select the sperm they want and to maintain stores of viable sperm to ensure a lifetime's fertility.

Den Boer
et al.

(p.
1506
) compared species of bees and ants with queens that either mate once or mate multiple times, and found that sperm competition has driven the evolution of compounds in the male accessory gland that protect a male's own sperm while damaging another male's sperm. To counteract the male effect, queens produce compounds that mitigate sperm destruction and maximize the number of her offspring.
Sailing on an Ocean of 0s and 1s
The Fourth Paradigm
Data-Intensive Scientific Discovery

Tony Hey, Stewart Tansley, and Kristin Tolle, Eds.

Microsoft Research, Redmond, WA, 2009. 286 pp. Paper, $46. ISBN 9780982544204. PDF at http://research.microsoft.com/en-us/collaboration/fourthparadigm/
Authors: Collins James P.
Published: March 2010

This set of essays from researchers and computer scientists describes the prospects and possibilities of data-intensive science.
Phenology Under Global Warming
Authors: Körner Christian , Basler David
Published: March 2010

In most temperate tree species, phenological events such as flowering and autumnal cessation of growth are not primarily controlled by temperature.
AMPA Receptors—Another Twist?
Authors: Farrant Mark , Cull-Candy Stuart G.
Published: March 2010

A protein expressed in brain controls the plasticity of synaptic transmission by regulating the properties of a neurotransmitter receptor.
Toward Organic All-Optical Switching
Authors: Haque Saif A. , Nelson Jenny
Published: March 2010

A sophisticated molecular design method yields an organic material for possible application in high-speed, all-optical communication.
Fairness in Modern Society
Authors: Hoff Karla
Published: March 2010

What features of a society motivate individuals to behave fairly?
Silicon Mystery Endures in Solved Anthrax Case
Authors: Bhattacharjee Yudhijit
Published: March 2010

Scientists say there is clear evidence that the high levels of silicon found in the anthrax used in the 2001 letter attacks came not from anything added to "weaponize" the anthrax spores but from the culture in which the spores were grown. So why did the mailed anthrax have such a high proportion of spores with a silicon signature in comparison to most other anthrax samples?
MIT Engineering Dean Tapped to Head NSF
Authors: Mervis Jeffrey
Published: March 2010

The dean of engineering at the Massachusetts Institute of Technology, Subra Suresh, is in line to become the next director of the U.S. National Science Foundation (NSF),
Science
has learned.
Hardy Cotton-Munching Pests Are Latest Blow to GM Crops
Authors: Bagla Pallava
Published: March 2010

Monsanto has revealed that a common insect pest has developed resistance to its flagship genetically modified (GM) product in India. Monsanto claims that the finding "is the first case of field-relevant resistance to
Cry1Ac
products, anywhere in the world."
Polish Science Reforms Bring Fear and Hope
Authors: Pain Elisabeth
Published: March 2010

The Polish Parliament this month began voting on legislation creating a new national agency charged with distributing competitive grants for frontier research.
Male Rivalry Extends to Sperm in Female Reproductive Tract
Authors: Pennisi Elizabeth
Published: March 2010

Two papers published by
Science
this week, one on work in ants and bees and the other on work in fruit flies, demonstrate that sperm competition between males continues even after the sperm enters the female.
Spirit Is Willing, Though Weak
Authors: Kerr Richard A.
Published: March 2010

At the Lunar and Planetary Science Conference, there was talk of resurrecting the Spirit rover, which has been stuck since January, or at least a realistic prospect of a return to limited mobility. NASA missions are indeed hard to kill.
The 74-Kilodalton Immunodominant Antigen of the Pathogenic OomycetePythium insidiosumIs a Putative Exo-1,3-ß-Glucanase
Authors: Krajaejun Theerapong , Keeratijarut Angsana , Sriwanichrak Kanchana , Lowhnoo Tassanee , Rujirawat Thidarat , Petchthong Thanom , Yingyong Wanta , Kalambaheti Thareerat , Smittipat Nat , Juthayothin Tada , Sullivan Thomas D.
Published: March 2010

The oomycetous, fungus-like, aquatic organismPythium insidiosumis the causative agent of pythiosis, a life-threatening infectious disease of humans and animals living in tropical and subtropical areas of the world. Common sites of infection are the arteries, eyes, cutaneous/subcutaneous tissues, and gastrointestinal tract. Diagnosis of pythiosis is time-consuming and difficult. Radical excision of the infected organs is the main treatment for pythiosis because conventional antifungal drugs are ineffective. An immunotherapeutic vaccine prepared fromP. insidiosumcrude extract showed limited efficacy in the treatment of pythiosis patients. Many pythiosis patients suffer lifelong disabilities or die from an advanced infection. Recently, we identified a 74-kDa major immunodominant antigen ofP. insidiosumwhich could be a target for development of a more effective serodiagnostic test and vaccines. Mass spectrometric analysis identified two peptides of the 74-kDa antigen (s74-1 and s74-2) which perfectly matched a putative exo-1,3-ß-glucanase (EXO1) ofPhytophthora infestans. Using degenerate primers derived from these peptides, a 1.1-kb product was produced by PCR, and its sequence was found to be homologous to that of theP. infestansexo-1,3-ß-glucanase gene,EXO1. Enzyme-linked immunosorbent assays targeting the s74-1 and s74-2 synthetic peptides demonstrated that the 74-kDa antigen was highly immunoreactive with pythiosis sera but not with control sera. Phylogenetic analysis using part of the 74-kDa protein-coding sequence divided 22 Thai isolates ofP. insidiosuminto two clades. Further characterization of the putativeP. insidiosumglucanase could lead to new diagnostic tests and to antimicrobial agents and vaccines for the prevention and management of the serious and life-threatening disease of pythiosis.
Identification of Cytokines in Whole Blood for Differential Diagnosis of Tuberculosis versus Pneumonia
Authors: Su Wen-Lin , Perng Wann-Cherng , Huang Ching-Hui , Yang Cheng-Yu , Wu Chin-Pyng , Chang Feng-Yee , Chen Jenn-Han
Published: March 2010

Differentiating tuberculosis (TB) from pneumonia remains a challenge. We evaluated the cytokine profiles of whole blood cells from patients with TB (n= 38) or pneumonia (n= 30) and from healthy individuals (n= 30) before and after stimulating cells with ESAT-6 or lipopolysaccharide (LPS). When the percent change in the levels of gamma interferon (IFN-γ) after stimulation with ESAT-6 was used in receiver operating characteristics (ROC) analysis (a graphic method to determine the diagnostic accuracy of a test) to identify a patient with TB, the area under the curve (AUC) was 90.4%, and a cutoff point of a 3.59% change produced a corresponding sensitivity, specificity, and accuracy of over 80%. When the change in IFN-γ after stimulation of blood cells with LPS was used to identify a patient with pneumonia, the AUC reached 89.1%, and a cutoff point of 3.59% produced a sensitivity, specificity, and accuracy of approximately 80% each. When the change in interleukin-12 (IL-12) after stimulation of blood cells with LPS was selected to define a patient with pneumonia, the AUC was 85.2%, and a cutoff point of 2.08% gave a sensitivity, specificity, and accuracy of 80.0%, 78.9%, and 79.4%, respectively. We conclude that the percent change in IFN-γ after stimulation of whole blood cells with ESAT-6 may differentiate patients with TB from patients with pneumonia. The percent change in IFN-γ and IL-12 after LPS stimulation of whole blood cells could differentiate patients with pneumonia from patients with TB.
Phylogenetic and Biological Characterization of Newcastle Disease Virus Isolates from Pakistan
Authors: Khan Taseer Ahmed , Rue Cary A. , Rehmani Shafqat Fatima , Ahmed Ayaz , Wasilenko Jamie L. , Miller Patti J. , Afonso Claudio L.
Published: March 2010

Eight Newcastle disease virus isolates from Pakistan were sequenced and characterized. A PCR matrix gene assay, designed to detect all avian paramyxovirus 1, did not detect four of the isolates. A new matrix gene test that detected all isolates was developed. Phylogenetic analysis and pathotyping confirmed that virulent viruses of different genotypes are circulating in Pakistan.
Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of
Mycobacterium tuberculosis
Infections
Authors: Juréen P. , Ängeby K. , Sturegård E. , Chryssanthou E. , Giske C. G. , Werngren J. , Nordvall M. , Johansson A. , Kahlmeter G. , Hoffner S. , Schön T.
Published: March 2010

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against
Mycobacterium tuberculosis
. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed ±1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [
C
max
]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against
Mycobacterium tuberculosis
.
Identification of Pathogenic Rare Yeast Species in Clinical Samples: Comparison between Phenotypical and Molecular Methods
Authors: Cendejas-Bueno Emilio , Gomez-Lopez Alicia , Mellado Emilia , Rodriguez-Tudela Juan L. , Cuenca-Estrella Manuel
Published: March 2010

Species identification using both phenotypic and molecular methods and antifungal susceptibility tests was carried out with 60 uncommon clinical yeasts. Our data show that phenotypic methods were insufficient for correct identification (only 25%) and that most of the wrongly identified strains showed a resistant antifungal profile.
Development and Evaluation of Oligonucleotide Chip Based on the 16S-23S rRNA Gene Spacer Region for Detection of Pathogenic Microorganisms Associated with Sepsis
Authors: Kim Cheol Min , Song Eun Sil , Jang Hyun Jung , Kim Hyun-Ju , Lee Sangyeop , Shin Jeong Hwan , Kim Sun Joo , Jeong Seok Hoon , Jeong Joseph , Koh Kwangnak , Choi Go Eun , Lee Eun Yup , Chang Chulhun L.
Published: March 2010

Oligonucleotide chips targeting the bacterial internal transcribed spacer region (ITS) of the 16S-23S rRNA gene, which contains genus- and species-specific regions, were developed and evaluated. Forty-three sequences were designed consisting of 1 universal, 3 Gram stain-specific, 9 genus-specific, and 30 species-specific probes. The specificity of the probes was confirmed using bacterial type strains including 54 of 52 species belonging to 18 genera. The performance of the probes was evaluated using 825 consecutive samples that were positive by blood culture in broth medium. Among the 825 clinical specimens, 708 (85.8%) were identified correctly by the oligonucleotide chip. Most (536 isolates, or 75.7%) were identified as staphylococci,
Escherichia coli
, or
Klebsiella pneumoniae
. Thirty-seven isolates (4.5%) did not bind to the corresponding specific probes. Most of these also were staphylococci,
E. coli
, or
K. pneumoniae
and accounted for 6.3% of total number of the species. Sixty-two specimens (7.5%) did not bind the genus- or species-specific probes because of lack of corresponding specific probes. Among them,
Acinetobacter baumannii
was the single most frequent isolate (26/62). The oligonucleotide chip was highly specific and sensitive in detecting the causative agents of bacteremia directly from positive blood cultures.
Real-Time Identification of Bacteria and
Candida
Species in Positive Blood Culture Broths by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry
Authors: Ferroni Agnès , Suarez Stéphanie , Beretti Jean-Luc , Dauphin Brunhilde , Bille Emmanuelle , Meyer Julie , Bougnoux Marie-Elisabeth , Alanio Alexandre , Berche Patrick , Nassif Xavier
Published: March 2010

Delays in the identification of microorganisms are a barrier to the establishment of adequate empirical antibiotic therapy of bacteremia. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) allows the identification of microorganisms directly from colonies within minutes. In this study, we have adapted and tested this technology for use with blood culture broths, thus allowing identification in less than 30 min once the blood culture is detected as positive. Our method is based on the selective recovery of bacteria by adding a detergent that solubilizes blood cells but not microbial membranes. Microorganisms are then extracted by centrifugation and analyzed by MALDI-TOF-MS. This strategy was first tested by inoculating various bacterial and fungal species into negative blood culture bottles. We then tested positive patient blood or fluid samples grown in blood culture bottles, and the results obtained by MALDI-TOF-MS were compared with those obtained using conventional strategies. Three hundred twelve spiked bottles and 434 positive cultures from patients were analyzed. Among monomicrobial fluids, MALDI-TOF-MS allowed a reliable identification at the species, group, and genus/family level in 91%, 5%, and 2% of cases, respectively, in 20 min. In only 2% of these samples, MALDI-TOF MS did not yield any result. When blood cultures were multibacterial, identification was improved by using specific databases based on the Gram staining results. MALDI-TOF-MS is currently the fastest technique to accurately identify microorganisms grown in positive blood culture broths.
Tuberculosis in Alpacas (
Lama pacos
) Caused by
Mycobacterium bovis
Authors: García-Bocanegra I. , Barranco I. , Rodríguez-Gómez I. M. , Pérez B. , Gómez-Laguna J. , Rodríguez S. , Ruiz-Villamayor E. , Perea A.
Published: March 2010

We report three cases of tuberculosis in alpacas from Spain caused by
Mycobacterium bovis
. The animals revealed two different lesional patterns. Mycobacterial culture and PCR assay yielded positive results for
M. bovis
. Molecular typing of the isolates identified spoligotype SB0295 and identical variable-number tandem repeat (VNTR) allele sizes.
HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7
Authors: Breckpot Karine , Escors David , Arce Frederick , Lopes Lucienne , Karwacz Katarzyna , Van Lint Sandra , Keyaerts Marleen , Collins Mary
Published: March 2010

Lentiviral vectors are promising vaccine vector candidates that have been tested extensively in preclinical models of infectious disease and cancer immunotherapy. They are also used in gene therapy clinical trials both for the
ex vivo
modification of cells and for direct
in vivo
injection. It is therefore critical to understand the mechanism(s) by which such vectors might stimulate the immune system. We evaluated the effect of lentiviral vectors on myeloid dendritic cells (DC), the main target of lentiviral transduction following subcutaneous immunization. The activation of DC cultures was independent of the lentiviral pseudotype but dependent on cell entry and reverse transcription.
In vivo
-transduced DC also displayed a mature phenotype, produced tumor necrosis factor alpha (TNF-α), and stimulated naive CD8
+
T cells. The lentiviral activation of DC was Toll-like receptor (TLR) dependent, as it was inhibited in TRIF/MyD88 knockout (TRIF/MyD88
−/−
) DC. TLR3
−/−
or TLR7
−/−
DC were less activated, and reverse transcription was important for the activation of TLR7
−/−
DC. Moreover, lentivirally transduced DC lacking TLR3 or TLR7 had an impaired capacity to induce antigen-specific CD8
+
T-cell responses. In conclusion, we demonstrated TLR-dependent DC activation by lentiviral vectors, explaining their immunogenicity. These data allow the rational development of strategies to manipulate the host's immune response to the transgene.
Ultrastructural Analysis of Virion Formation and Anterograde Intraaxonal Transport of the Alphaherpesvirus Pseudorabies Virus in Primary Neurons
Authors: Maresch Christina , Granzow Harald , Negatsch Alexandra , Klupp Barbara G. , Fuchs Walter , Teifke Jens P. , Mettenleiter Thomas C.
Published: March 2010

A hallmark of alphaherpesviruses is their capacity to be neuroinvasive and establish latent infections in neurons. After primary replication in epithelial cells at the periphery, entry into nerve endings occurs, followed by retrograde transport of nucleocapsids to the nucleus where viral transcription, genome replication, and nucleocapsid formation take place. Translocation of nucleocapsids to the cytoplasm is followed by axonal transport to infect synaptically linked neurons. Two modes of intraaxonal anterograde herpesvirus transport have been proposed: transport of complete, enveloped virions within vesicles (“married model”), and separate transport of capsids and envelopes (“subassembly model”). To assess this in detail for the alphaherpesvirus pseudorabies virus (PrV), we used high-resolution transmission electron microscopy of primary neuronal cultures from embryonic rat superior cervical ganglia after infection with wild-type and gB-deficient PrV. Our data show that intranuclear capsid maturation, nuclear egress and cytoplasmic secondary envelopment occur as in cultured nonpolarized cells (H. Granzow, F. Weiland, A. Jöns, B. G. Klupp, A. Karger, and T. C. Mettenleiter, J. Virol. 71:2072-2082, 1997). PrV virions were present in axons as enveloped particles within vesicles associated with microtubules and apparently leave the neuron by exocytosis primarily at the growth cone. Only a few nonenveloped nucleocapsids were found in the axon. The same picture was observed after infection by phenotypically complemented gB-deficient PrV, which is able to complete only a single round of replication. Our data thus support intraaxonal anterograde transport of enveloped PrV virions within vesicles following the “married model.”
Cleavage of Influenza Virus Hemagglutinin by Airway Proteases TMPRSS2 and HAT Differs in Subcellular Localization and Susceptibility to Protease Inhibitors
Authors: Böttcher-Friebertshäuser Eva , Freuer Catharina , Sielaff Frank , Schmidt Sarah , Eickmann Markus , Uhlendorff Jennifer , Steinmetzer Torsten , Klenk Hans-Dieter , Garten Wolfgang
Published: March 2010

Proteolytic cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is crucial for infectivity and virus spread. The proteases HAT (human airway trypsin-like protease) and TMPRSS2 (transmembrane protease serine S1 member 2) known to be present in the human airways were previously identified as proteases that cleave HA. We studied subcellular localization of HA cleavage and cleavage inhibition of seasonal influenza virus A/Memphis/14/96 (H1N1) and pandemic virus A/Hamburg/5/2009 (H1N1) in MDCK cells that express HAT and TMPRSS2 under doxycycline-induced transcriptional activation. We made the following observations: (i) HA is cleaved by membrane-bound TMPRSS2 and HAT and not by soluble forms released into the supernatant; (ii) HAT cleaves newly synthesized HA before or during the release of progeny virions and HA of incoming viruses prior to endocytosis at the cell surface, whereas TMPRSS2 cleaves newly synthesized HA within the cell and is not able to support the proteolytic activation of HA of incoming virions; and (iii) cleavage activation of HA and virus spread in TMPRSS2- and HAT-expressing cells can be suppressed by peptide mimetic protease inhibitors. The further development of these inhibitors could lead to new drugs for influenza treatment.
Coinfecting Prion Strains Compete for a Limiting Cellular Resource
Authors: Shikiya Ronald A. , Ayers Jacob I. , Schutt Charles R. , Kincaid Anthony E. , Bartz Jason C.
Published: March 2010

Prion strain interference can influence the emergence of a dominant strain from a mixture; however, the mechanisms underlying prion strain interference are poorly understood. In our model of strain interference, inoculation of the sciatic nerve with the drowsy (DY) strain of the transmissible mink encephalopathy (TME) agent prior to superinfection with the hyper (HY) strain of TME can completely block HY TME from causing disease. We show here that the deposition of PrP
Sc
, in the absence of neuronal loss or spongiform change, in the central nervous system corresponds with the ability of DY TME to block HY TME infection. This suggests that DY TME agent-induced damage is not responsible for strain interference but rather prions compete for a cellular resource. We show that protein misfolding cyclic amplification (PMCA) of DY and HY TME maintains the strain-specific properties of PrP
Sc
and replicates infectious agent and that DY TME can interfere, or completely block, the emergence of HY TME. DY PrP
Sc
does not convert all of the available PrP
C
to PrP
Sc
in PMCA, suggesting the mechanism of prion strain interference is due to the sequestering of PrP
C
and/or other cellular components required for prion conversion. The emergence of HY TME in PMCA was controlled by the initial ratio of the TME agents. A higher ratio of DY to HY TME agent is required for complete blockage of HY TME in PMCA compared to several previous
in vivo
studies, suggesting that HY TME persists in animals coinfected with the two strains. This was confirmed by PMCA detection of HY PrP
Sc
in animals where DY TME had completely blocked HY TME from causing disease.
Human Papillomavirus Type 16 E6/E7 Upregulation of Nucleophosmin Is Important for Proliferation and Inhibition of Differentiation
Authors: McCloskey Rachel , Menges Craig , Friedman Alan , Patel Daksha , McCance Dennis J.
Published: March 2010

The E6 and E7 oncoproteins of high-risk human papillomaviruses (HPVs) are together sufficient to cause cellular transformation. Nucleophosmin (NPM) was identified as a protein with increased levels in two-dimensional (2-D) gel analysis of human foreskin keratinocytes (HFKs) expressing E7 following methylcellulose-induced differentiation. Analysis of NPM expression in E7-expressing cells and E6- and E7-expressing cells in culture and in organotypic rafts confirmed the increased levels observed in 2-D gel analysis. The elevated expression of NPM was determined to be posttranscriptional and was attributed to increased v-akt murine thymoma viral oncogene (AKT) activity in the E6- and E7-expressing cells. Depletion of NPM caused a reduction in the replicative capacity of E7- and E6/E7-expressing HFKs and an increase in markers of differentiation. Also, the p53 and pRb tumor suppressor levels are increased with the knockdown of NPM in E6/E7-expressing cells, and, interestingly, p14
ARF
is relocalized from the nucleolus to the nucleoplasm and cytoplasm in these cells. The results show for the first time that NPM is required for the proliferation and inhibition of differentiation observed in HPV E6- and E7-expressing primary cells.
Tax 1-Independent Induction of Vascular Endothelial Growth Factor in Adult T-Cell Leukemia Caused by Human T-Cell Leukemia Virus Type 1
Authors: Watters Karen M. , Dean Jonathan , Gautier Virginie , Hall William W. , Sheehy Noreen
Published: March 2010

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). Elevated expression of vascular endothelial growth factor (VEGF) in ATL patients is associated with leukemic cell invasion and infiltration in different organs. The regulatory protein Tax 1 encoded by HTLV-1 plays a pivotal role in T-cell transformation by deregulating the function and expression of several cellular factors. In the present study, we examined the effect of Tax 1 on VEGF expression at transcriptional and posttranscriptional levels in order to elucidate the regulatory mechanisms involved. Using functional assays, we demonstrate that Tax 1 downregulates the VEGF promoter through a cluster of Sp1 sites located close to the transcriptional start site. Using gel mobility shift assays, we show that Tax 1 reduced Sp1:DNA complex formation. We demonstrate that the level of secreted VEGF was significantly lower in Tax 1-transfected 293T cells compared to nontransfected cells, which is consistent with the observed downregulatory effect of Tax 1 at the transcription level. We showed that VEGF was secreted by HTLV-1-transformed and nontransformed cells, irrespective of Tax 1 expression. Overall our data indicate that, contrary to a previous report, Tax 1 downregulates VEGF expression and suggest there are Tax 1-independent mechanisms of VEGF activation in ATL.
Widespread Antisense Transcription in Escherichia coli
Authors: Dornenburg James E. , DeVita Anne M. , Palumbo Michael J. , Wade Joseph T.
Published: March 2010

The vast majority of annotated transcripts in bacteria are mRNAs. Here we identify ~1,000 antisense transcripts in the model bacterium
Escherichia coli
. We propose that these transcripts are generated by promiscuous transcription initiation within genes and that many of them regulate expression of the overlapping gene.

IMPORTANCE
The vast majority of known genes in bacteria are protein coding, and there are very few known antisense transcripts within these genes, i.e., RNAs that are encoded opposite the gene. Here we demonstrate the existence of ~1,000 antisense RNAs in the model bacterium
Escherichia coli
. Given the high potential for these RNAs to base pair with mRNA of the overlapping gene and the likelihood of clashes between transcription complexes of antisense and sense transcripts, we propose that antisense RNAs represent an important but overlooked class of regulatory molecule.
Optimising use of thiopurines in inflammatory bowel disease
Authors: Raj Lawrence Sunder , Hawthorne A Barney
Published: March 2010

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the most widely used immunosuppressive therapies in inflammatory bowel disease. Pretreatment measurement of thiopurine methyltransferase (TPMT) activity is recommended and although conventional practice is to use a dose of 2 mg/kg AZA (1 mg/kg 6-MP), higher doses of 2.5 mg/kg AZA or more may be required in some patients, particularly if TPMT activity is high. Dose raising is limited by toxicity, and a robust monitoring system is mandatory. Patients with side effects to AZA may tolerate 6-MP but pancreatitis is a contraindication to switching. Metabolite monitoring is not widely available but may be useful, particularly if non-compliance is possible or where metabolite shunting to 6-methylmercaptopurine is suspected, on the basis of non-response or toxicity. It may allow dose optimisation before switching to alternative immunosuppressants. The drug appears safe in pregnancy and breast feeding. Long term duration of therapy is a balance between benefits in relation to the underlying disease extent, activity and aggressiveness, and the risk of neoplasia, particularly lymphoma.
EFFECTS OF MOTION ON EPIDEMIC SPREADING
Authors: BUSCARINO ARTURO , DI STEFANO AGNESE , FORTUNA LUIGI , FRASCA MATTIA , LATORA VITO
Published: March 2010

The study of social networks, and in particular those aspects related to disease spreading, has recently attracted considerable attention in the scientific community. In this paper, we investigate the effect of motion on the spread of diseases in dynamical networks of mobile agents. In order to simulate the long distance displacements empirically observed in real human movements, we consider different motion rules, such as random walks with the addition of jumps or Lévy flights. We compare the epidemic thresholds found in dynamical networks of mobile agents with the analogous expressions for static networks. We discuss the existing relations between dynamical networks of random walkers with jumps and static small-world networks, and those between systems of Lévy walkers and scale-free networks.
EXCITABLE NETWORKS: NONEQUILIBRIUM CRITICALITY AND OPTIMUM TOPOLOGY
Authors: TORRES J. J. , DE FRANCISCIS S. , JOHNSON S. , MARRO J.
Published: March 2010

Excitable media may be modeled as simple extensions of the Amari–Hopfield network with dynamic attractors. Some nodes chosen at random remain temporarily quiet, and some of the edges are switched off to adjust the network connectivity, while the weights of the other edges vary with activity. We conclude on the optimum wiring topology and describe nonequilibrium phases and criticality at the edge of irregular behavior.
ALTERNATIVE METHODS TO EXTRACT THE HARDNESS AND ELASTIC MODULUS OF THIN FILMS FROM NANOINDENTATION LOAD-DISPLACEMENT DATA
Authors: KUMAR AMIT , ZENG KAIYANG
Published: March 2010

This paper presents alternative analysis methodologies to extract the elastic modulus and hardness of the ultra-thin films from nanoindentation load-displacement data, especially when the film thickness is only few hundred nanometers or less. At such film thickness, the conventional analysis methods for nanoindentation usually do not give accurate film properties due to the substrate effect. The new methods are capable to show how to determine the film-only properties and how the substrates affect the nanoindentation measurement, especially for ultra thin films. These methods give accurate results for nanoindentation of various metallic, ceramic and polymeric films. It also reveals the differences between the use of high-resolution nanoindentation set-up and normal nanoindentation set-up on the same films. The relationships between the mechanical properties and film thickness are also discussed.
SINGULAR STRESS ANALYSIS IN FLAT PUNCH PROBLEM OF ELASTIC HALF-PLANE
Authors: CHEN Y. Z. , LIN X. Y. , WANG Z. X.
Published: March 2010

Singular stress analysis in the flat punch problem of half-plane is carried out. The angle distribution for the stress components is also achieved in an explicit form. Followed a similar study in the punch analysis, the punch singular stress factor (abbreviated as PSSF) is defined from the singular stress distribution. For the problems of two punches or three punches, solutions in a closed form are obtained. The obtained solutions may depend on some complete elliptical integrals. Meantime, the exerting location of the resultant force for punches is also determined. Interactions between punches are also addressed. Several numerical examples with the calculated results are presented.
DISSIPATIVE PARTICLE DYNAMICS IN SOFT MATTER AND POLYMERIC APPLICATIONS — A REVIEW
Authors: MOEENDARBARY E. , NG T. Y. , ZANGENEH M.
Published: March 2010

Computer simulations and in particular mesoscopic simulation techniques such as the dissipative particle dynamics (DPD) technique, enable researchers to study the complexities of soft material and polymeric systems by performing in silico experimentations alongside in vivo experiments. In addition, these mesoscopic simulations allow scientists and engineers to characterize and optimize the actual experiments in a more efficient manner. The DPD is one the most reliable mesoscopic simulation techniques for phenomenological investigation of soft matter and polymeric systems. In this review, which is complimentary to an earlier review also by the present authors on DPD methodology and complex fluid application (Moeendarbary et al., 2009), we categorize and review the notable published works, and document efforts that applied the DPD simulation technique to various important soft matter and polymeric applications, over the last decade.
EFFECT OF TRANSVERSE NORMAL AND SHEAR DEFORMATION ON A FIBER-REINFORCED VISCOELASTIC BEAM RESTING ON TWO-PARAMETER ELASTIC FOUNDATIONS
Authors: ZENKOUR A. M. , ALLAM M. N. M. , SOBHY MOHAMMED
Published: March 2010

This article investigates the effect of transverse normal and shear deformations on a fiber-reinforced viscoelastic beams resting on two-parameter (Pasternak's) elastic foundations. The results are obtained by the refined sinusoidal shear deformation beam theory and compared with those obtained by the simple sinusoidal shear deformation beam theory, Timoshenko first-order shear deformation beam theory as well as Euler-Bernoulli classical beam theory. The effects of foundation stiffness on bending of viscoelastic composite beam are presented. The effective moduli methods are used to derive the governing equations of viscoelastic beams. The influences of several parameters, such as length-to-depth ratio, foundation stiffness, time parameter and other parameters on mechanical behavior of composite beams resting on Pasternak's foundations are investigated. Numerical results are presented and conclusions are formulated.
COMMD1 downregulates the epithelial sodium channel through Nedd4–2
Authors: Ke Ying , Butt A. Grant , Swart Marianne , Liu Yong Feng , McDonald Fiona J.
Published: March 2010

The epithelial sodium channel (ENaC) is important for the long-term control of Na+ homeostasis and blood pressure. Our previous studies demonstrated that Copper Metabolism Murr1 Domain-containing protein 1 (COMMD1; previously known as Murr1), a protein involved in copper metabolism, inhibited amiloride-sensitive current in Xenopus laevis oocytes expressing ENaC ( J Biol Chem 279: 5429, 2004). In this study, we report that COMMD1 inhibits amiloride-sensitive current in mammalian epithelial cells expressing ENaC, that the COMM domain of COMMD1 is sufficient for this effect, and that knockdown of COMMD1 increases amiloride-sensitive current. COMMD1 is coexpressed with ENaC in rat kidney medulla cells. COMMD1 increased ubiquitin modification of ENaC and decreased its cell surface expression. COMMD1 abolished insulin-stimulated amiloride-sensitive current and attenuated the stimulation of current by activated serum and glucocorticoid-regulated kinase (SGK1). COMMD1 was found to interact with both SGK1 and Akt1/protein kinase B, and knockdown of COMMD1 enhanced the stimulatory effect of both SGK1 and Akt1 on amiloride-sensitive current. COMMD1's effects were reduced in the presence of ENaC proteins containing PY motif mutations, abolished in the presence of a dominant negative form of Nedd4–2, and knockdown of COMMD1 reduced the inhibitory effect of Nedd4–2 on ENaC, but did not enhance current when Nedd4–2 was knocked down. These data suggest that COMMD1 modulates Na+ transport in epithelial cells through regulation of ENaC cell surface expression and this effect is likely mediated via Nedd4–2.
Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion
Authors: Gerritsen Karin G. , Peters Hilde P. , Nguyen Tri Q. , Koeners Maarten P. , Wetzels Jack F. , Joles Jaap A. , Christensen Erik I. , Verroust Pierre J. , Li Dongxia , Oliver Noelynn , Xu Leon , Kok Robbert J. , Goldschmeding Roel
Published: March 2010

Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal expression. We investigated how tubular dysfunction affects urinary CTGF levels. To study this, we administered recombinant CTGF intravenously to rodents. We used both full-length CTGF and the NH2-terminal fragment, since the NH2-fragment is the predominant form detected in urine. Renal CTGF extraction, determined by simultaneous arterial and renal vein sampling, was 18 ± 3% for full-length CTGF and 21 ± 1% for the NH2-fragment. Fractional excretion was very low for both CTGFs (0.02 ± 0.006% and 0.10 ± 0.02%, respectively), indicating that >99% of the extracted CTGF was metabolized by the kidney. Immunohistochemistry revealed extensive proximal tubular uptake of CTGF in apical endocytic vesicles and colocalization with megalin. Urinary CTGF was elevated in megalin- and cubilin-deficient mice but not in cubilin-deficient mice. Inhibition of tubular reabsorption by Gelofusine reduced renal uptake of CTGF and increased urinary CTGF. In healthy volunteers, Gelofusine also induced an increase of urinary CTGF excretion, comparable to the increase of β2-microglobulin excretion ( r = 0.99). Furthermore, urinary CTGF correlated with β2-microglobulin ( r = 0.85) in renal disease patients ( n = 108), and only β2-microglobulin emerged as an independent determinant of urinary CTGF. Thus filtered CTGF is normally reabsorbed almost completely in proximal tubules via megalin, and elevated urinary CTGF may largely reflect proximal tubular dysfunction.
Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice
Authors: Yoshiyama Mitsuharu , Araki Isao , Kobayashi Hideki , Zakoji Hidenori , Takeda Masayuki
Published: March 2010

Sex-specific differences in activity of the lower urinary tract (LUT) responding to acid irritation in mice have been revealed. This study, using continuous infusion cystometry with acetic acid (AA; pH 3.0), was conducted to examine whether the transient receptor potential vanilloid type 1 (TRPV1) channels expressed in the mouse LUT are involved in the sex difference in functional responses of the bladder and urethra to irritation. No differences were found between effects of capsazepine (a TRPV1 blocker; 100 μM) and those of its vehicle on any of the cystometric changes by intravesical AA in either female or male mice. However, capsazepine eliminated the acid-induced sex differences in parameters associated with bladder contraction phase (i.e., maximal voiding pressure, closing peak pressure, 2nd-phase contraction, bladder contraction duration), whereas capsazepine did not affect those in parameters associated with bladder-filling period (i.e., intercontraction interval, actual collecting time). In males, capsazepine reduced the number of bladder contractions accompanying fluid dribbling at 2nd-phase contraction, which is indicative of the urethral response to irritation, whereas in females it increased the number. Together, these results suggest the possibilities that TRPV1 channels in the bladder and urethra are involved in the sex difference in the LUT response to acid irritation and that these participate, e.g., via “cross talk” between the bladder and urethra, in the fine-tuning of intravesical pressure (or bladder emptying) at the bladder contraction phase under irritated LUT conditions but not in sensing for bladder filling during the storage period, although the contribution of the mechanism may be small.
Myocellular basis for tapering in competitive distance runners
Authors: Luden Nicholas , Hayes Erik , Galpin Andrew , Minchev Kiril , Jemiolo Bozena , Raue Ulrika , Trappe Todd A. , Harber Matthew P. , Bowers Ted , Trappe Scott
Published: March 2010

The purpose of this study was to examine the effects of a 3-wk taper on the physiology of competitive distance runners. We studied seven collegiate distance runners (20 ± 1 yr, 66 ± 1 kg) before and after a 3-wk taper. The primary measures included 8-km cross-country race performance, gastrocnemius single muscle fiber size and function (peak force, shortening velocity, and power), baseline and exercise-induced gene expression 4 h after a standardized 8-km run, citrate synthase activity, and maximal and submaximal cardiovascular physiology (oxygen consumption, ventilation, heart rate, and respiratory exchange ratio). Race performance improved by 3% following taper ( P < 0.05). Myosin heavy chain (MHC) IIa fiber diameter (+7%, P < 0.05), peak force (+11%, P = 0.06), and absolute power (+9%, P < 0.05) increased following taper. In addition to the MHC IIa adaptations, taper elicited a distinct postexercise gene response. Specifically, the induction of MuRF-1 was attenuated following taper, whereas MRF4, HSP 72, and MT-2A displayed an exaggerated response ( P < 0.05). No changes were observed in MHC I size or function, baseline gene expression, citrate synthase activity, or cardiovascular function. Our findings show that tapered training in competitive runners promoted MHC IIa fiber remodeling and an altered transcriptional response following the same exercise perturbation, with no adverse affects on aerobic fitness. Together, these results provide a myocellular basis for distance runners to taper in preparation for peak performance.
Load Rather Than Length Sensitive Feedback Contributes to Soleus Muscle Activity During Human Treadmill Walking
Authors: af Klint Richard , Mazzaro Nazarena , Nielsen Jens Bo , Sinkjaer Thomas , Grey Michael J.
Published: March 2010

Walking requires a constant adaptation of locomotor output from sensory afferent feedback mechanisms to ensure efficient and stable gait. We investigated the nature of the sensory afferent feedback contribution to the soleus motoneuronal drive and to the corrective stretch reflex by manipulating body load and ankle joint angle. The volunteers walked on a treadmill (∼3.6 km/h) connected to a body weight support (BWS) system. To manipulate the load sensitive afferents the level of BWS was switched between 5 and 30% of body weight. The effect of transient changes in BWS on the soleus stretch reflex was measured by presenting dorsiflexion perturbations (∼5°, 360–400°/s) in mid and late stances. Short (SLRs) and medium latency reflexes (MLRs) were quantified in a 15 ms analysis window. The MLR decreased with decreased loading ( P = 0.045), but no significant difference was observed for the SLR ( P = 0.13). Similarly, the effect of the BWS was measured on the unload response, i.e., the depression in soleus activity following a plantar-flexion perturbation (∼5.6°, 203–247°/s), quantified over a 50 ms analysis window. The unload response decreased with decreased load ( P > 0.001), but was not significantly affected ( P = 0.45) by tizanidine induced depression of the MLR ( P = 0.039, n = 6). Since tizanidine is believed to depress the group II afferent pathway, these results are consistent with the idea that force-related afferent feedback contributes both to the background locomotor activity and to the medium latency stretch reflex. In contrast, length-related afferent feedback may contribute to only the medium latency stretch reflex.
Spatial Coincidence of Intentional Actions Modulates an Implicit Visuomotor Control
Authors: Abekawa Naotoshi , Gomi Hiroaki
Published: March 2010

We investigated a visuomotor mechanism contributing to reach correction: the manual following response (MFR), which is a quick response to background visual motion that frequently occurs as a reafference when the body moves. Although several visual specificities of the MFR have been elucidated, the functional and computational mechanisms of its motor coordination remain unclear mainly because it involves complex relationships among gaze, reaching target, and visual stimuli. To directly explore how these factors interact in the MFR, we assessed the impact of spatial coincidences among gaze, arm reaching, and visual motion on the MFR. When gaze location was displaced from the reaching target with an identical visual motion kept on the retina, the amplitude of the MFR significantly decreased as displacement increased. A factorial manipulation of gaze, reaching-target, and visual motion locations showed that the response decrease is due to the spatial separation between gaze and reaching target but is not due to the spatial separation between visual motion and reaching target. Additionally, elimination of visual motion around the fovea attenuated the MFR. The effects of these spatial coincidences on the MFR are completely different from their effects on the perceptual mislocalization of targets caused by visual motion. Furthermore, we found clear differences between the modulation sensitivities of the MFR and the ocular following response to spatial mismatch between gaze and reaching locations. These results suggest that the MFR modulation observed in our experiment is not due to changes in visual interaction between target and visual motion or to modulation of motion sensitivity in early visual processing. Instead the motor command of the MFR appears to be modulated by the spatial relationship between gaze and reaching.