bluuebunny/crossref_metadata_2025 huggingface dataset:
Oestradiol decreases colonic permeability through oestrogen receptor β‐mediated up‐regulation of occludin and junctional adhesion molecule‐A in epithelial cells
Authors: Braniste Viorica , Leveque Mathilde , Buisson‐Brenac Claire , Bueno Lionel , Fioramonti Jean , Houdeau Eric
Published: May 2009

Oestradiol modulates paracellular permeability and tight junction (TJ) function in endothelia and reproductive tissues, but whether the ovarian hormones and cycle affect the paracellular pathway in the intestinal epithelium remains unclear. Oestrogen receptors (ERs) are expressed in intestinal epithelial cells, and oestradiol regulates epithelium formation. We examined the effects of oestrous cycle stage, oestradiol benzoate (EB), and progesterone (P) on colonic paracellular permeability (CPP) in the female rat, and whether EB affects expression of the TJ proteins in the rat colon and the human colon cell line Caco‐2. In cyclic rats, CPP was determined through lumen‐to‐blood 51Cr‐labelled EDTA clearance, and in Ussing chambers for dextran permeability. CPP was also examined in ovariectomized (OVX) rats treated with P or EB, with and without the ER antagonist ICI 182,780, or with the selective agonists for ERα (propyl pyrazole triol; PPT) or ERβ (diarylpropionitrile; DPN). In oestrus rats, CPP was reduced (P < 0.01) relative to dioestrus. In OVX rats, EB dose‐dependently decreased CPP, an effect mimicked by DPN and blocked by ICI 182,780, whereas P had no effect. Oestradiol increased occludin mRNA and protein in the colon (P < 0.05), but not zona occludens (ZO)‐1. Further, EB and DPN enhanced occludin and junctional adhesion molecule (JAM)‐A expression in Caco‐2 cells without change in ZO‐1, an effect blocked by ICI 182,780. These data show that oestrogen reinforces intestinal epithelial barrier through ERβ‐mediated up‐regulation of the transmembrane proteins occludin and JAM‐A determining paracellular spaces. These findings highlight the importance of the ERβ pathway in the control of colonic paracellular transport and mucosal homeostasis.
Multiple forms of activity‐dependent intrinsic plasticity in layer V cortical neurones in vivo
Authors: Paz Jeanne T. , Mahon Séverine , Tiret Pascale , Genet Stéphane , Delord Bruno , Charpier Stéphane
Published: May 2009

Synaptic plasticity is classically considered as the neuronal substrate for learning and memory. However, activity‐dependent changes in neuronal intrinsic excitability have been reported in several learning‐related brain regions, suggesting that intrinsic plasticity could also participate to information storage. Compared to synaptic plasticity, there has been little exploration of the properties of induction and expression of intrinsic plasticity in an intact brain. Here, by the means of in vivo intracellular recordings in the rat we have examined how the intrinsic excitability of layer V motor cortex pyramidal neurones is altered following brief periods of repeated firing. Changes in membrane excitability were assessed by modifications in the discharge frequency versus injected current (F–I) curves. Most (∼64%) conditioned neurones exhibited a long‐lasting intrinsic plasticity, which was expressed either by selective changes in the current threshold or in the slope of the F–I curve, or by concomitant changes in both parameters. These modifications in the neuronal input–output relationship led to a global increase or decrease in intrinsic excitability. Passive electrical membrane properties were unaffected by the intracellular conditioning, indicating that intrinsic plasticity resulted from modifications of voltage‐gated ion channels. These results demonstrate that neocortical pyramidal neurones can express in vivo a bidirectional use‐dependent intrinsic plasticity, modifying their sensitivity to weak inputs and/or the gain of their input–output function. These multiple forms of experience‐dependent intrinsic changes, which expand the computational abilities of individual neurones, could shape new network dynamics and thus might participate in the formation of mnemonic motor engrams.
Direct Measurement of Nonuniform Large Deformations in Soft Tissues During Uniaxial Extension
Authors: Doehring Todd C. , Kahelin Michael , Vesely Ivan
Published: May 2009

Understanding the complex relationships between microstructural organization and macromechanical function is fundamental to our knowledge of the differences between normal, diseased/injured, and healing connective tissues. The long-term success of functional tissue-engineered constructs or scaffolds may largely depend on our understanding of the structural organization of the original tissue. Although innovative techniques have been used to characterize and measure the microstructural properties of collagen fibers, a large gap remains in our knowledge of the behavior of intermediate scale (i.e., “mesostructural”) groups of fiber bundles in larger tissue samples. The objective of this study was to develop a system capable of directly measuring deformations of these smaller mesostructures during application of controlled loads. A novel mesostructural testing system (MSTS) has been developed to apply controlled multiaxial loads to medium (meso-) scale tissue specimens, while directly measuring local nonuniform deformations using synchronized digital video capture and “markerless” image correlation. A novel component of the MSTS is the use of elliptically polarized light to enhance collagen fiber contrast, providing the necessary texture for accurate markerless feature tracking of local fiber deformations. In this report we describe the components of the system, its calibration and validation, and the results from two different tissues: the porcine aortic valve cusp and the bovine pericardium. Validation tests on prepared samples showed maximum error of direct strain measurement to be 0.3%. Aortic valve specimens were found to have larger inhomogeneous strains during tensile testing than bovine pericardium. Clamping effects were more pronounced for the valve specimens. A new system for direct internal strain measurement in connective tissues during application of controlled loads has been developed and validated. The results from the two different tissues show that significant inhomogeneous deformations can occur even in simple tensile testing experiments.
Comparison of Near-Wall Hemodynamic Parameters in Stented Artery Models
Authors: Duraiswamy Nandini , Schoephoerster Richard T. , Moore James E.
Published: May 2009

Four commercially available stent designs (two balloon expandable—Bx Velocity and NIR, and two self-expanding—Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of 10±5 dyn/cm2). Mesh independence was determined from convergence (<10%) of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent (2.9 dyn/cm2) compared with the others (5.8 dyn/cm2 for the Bx Velocity stent, 5.0 dyn/cm2 for the Aurora stent, and 5.3 dyn/cm2 for the NIR stent). Regions of low mean WSS (<5 dyn/cm2) and elevated WSS gradients (>20 dyn/cm3) were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.
Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena
Authors: Ateshian Gerard A. , Rajan Vikram , Chahine Nadeen O. , Canal Clare E. , Hung Clark T.
Published: May 2009

Cartilage is a hydrated soft tissue whose solid matrix consists of negatively charged proteoglycans enmeshed within a fibrillar collagen network. Though many aspects of cartilage mechanics are well understood today, most notably in the context of porous media mechanics, there remain a number of responses observed experimentally whose prediction from theory has been challenging. In this study the solid matrix of cartilage is modeled with a continuous fiber angular distribution, where fibers can only sustain tension, swelled by the osmotic pressure of a proteoglycan ground matrix. It is shown that this representation of cartilage can predict a number of observed phenomena in relation to the tissue’s equilibrium response to mechanical and osmotic loading, when flow-dependent and flow-independent viscoelastic effects have subsided. In particular, this model can predict the transition of Poisson’s ratio from very low values in compression (∼0.02) to very high values in tension (∼2.0). Most of these phenomena cannot be explained when using only three orthogonal fiber bundles to describe the tissue matrix, a common modeling assumption used to date. The main picture emerging from this analysis is that the anisotropy of the fibrillar matrix of articular cartilage is intimately dependent on the mechanism of tensed fiber recruitment, in the manner suggested by our recent theoretical study (Ateshian, 2007, ASME J. Biomech. Eng., 129(2), pp. 240–249).
Three-Dimensional Geometrical Characterization of Abdominal Aortic Aneurysms: Image-Based Wall Thickness Distribution
Authors: Martufi Giampaolo , Di Martino Elena S. , Amon Cristina H. , Muluk Satish C. , Finol Ender A.
Published: May 2009

The clinical assessment of abdominal aortic aneurysm (AAA) rupture risk is based on the quantification of AAA size by measuring its maximum diameter from computed tomography (CT) images and estimating the expansion rate of the aneurysm sac over time. Recent findings have shown that geometrical shape and size, as well as local wall thickness may be related to this risk; thus, reliable noninvasive image-based methods to evaluate AAA geometry have a potential to become valuable clinical tools. Utilizing existing CT data, the three-dimensional geometry of nine unruptured human AAAs was reconstructed and characterized quantitatively. We propose and evaluate a series of 1D size, 2D shape, 3D size, 3D shape, and second-order curvature-based indices to quantify AAA geometry, as well as the geometry of a size-matched idealized fusiform aneurysm and a patient-specific normal abdominal aorta used as controls. The wall thickness estimation algorithm, validated in our previous work, is tested against discrete point measurements taken from a cadaver tissue model, yielding an average relative difference in AAA wall thickness of 7.8%. It is unlikely that any one of the proposed geometrical indices alone would be a reliable index of rupture risk or a threshold for elective repair. Rather, the complete geometry and a positive correlation of a set of indices should be considered to assess the potential for rupture. With this quantitative parameter assessment, future research can be directed toward statistical analyses correlating the numerical values of these parameters with the risk of aneurysm rupture or intervention (surgical or endovascular). While this work does not provide direct insight into the possible clinical use of the geometric parameters, we believe it provides the foundation necessary for future efforts in that direction.
Differential Translocation of Nuclear Factor-KappaB in a Cardiac Muscle Cell Line Under Gravitational Changes
Authors: Kwon Ohwon , Tranter Michael , Jones W. Keith , Sankovic John M. , Banerjee Rupak K.
Published: May 2009

Microgravity (micro-g) environments have been shown to elicit dysregulation of specific genes in a wide assay of cell types. It is known that the activation of transcription factors and molecular signaling pathways influence various physiological outcomes associated with stress and adaptive responses. Nuclear factor-kappa B (NF-κB) is one of the most prevailing oxidation-sensitive transcription factors. It is hypothesized that simulated microgravity would activate NF-κB and its downstream transcriptional networks, thus suggesting a role for NF-κB in microgravity induced muscle atrophy. To investigate the activation of NF-κB in a rat cardiac cell line (H9c2) under micro-g, rotating wall vessel bioreactors were used to simulate micro-g conditions. Western blotting revealed that mean nuclear translocation of NF-κB p65 subunit was 69% for micro-g and 46% for unit-g dynamic control as compared with a 30 min TNF-α positive control (p<0.05, n=3). The results from western blots were confirmed by enzyme-linked immunosorbent assay, which showed 66% for micro-g and 45% for dynamic control as compared with positive control (p<0.05, n=3). These results show significant differential translocation of NF-κB p65 under simulated micro-g. These results may be expanded upon to explain physiological changes such as muscle atrophy and further identify the regulatory pathways and effector molecules activated under exposure to micro-g.
Novel
pfdhps
Haplotypes among Imported Cases of
Plasmodium falciparum
Malaria in the United Kingdom
Authors: Sutherland Colin J. , Fifer Helen , Pearce Richard J. , bin Reza Faisal , Nicholas Meredydd , Haustein Thomas , Njimgye-Tekumafor Njah E. , Doherty Justin F. , Gothard Philip , Polley Spencer D. , Chiodini Peter L.
Published: May 2009

Treatment of acute malaria caused by
Plasmodium falciparum
may include long-half-life drugs, such as the antifolate combination sulfadoxine-pyrimethamine (SP), to provide posttreatment chemoprophylaxis against parasite recrudescence or delayed emergence from the liver. An unusual case of
P. falciparum
recrudescence in a returned British traveler who received such a regimen, as well as a series of 44 parasite isolates from the same hospital, was analyzed by PCR and direct DNA sequencing for the presence of markers of parasite resistance to chloroquine and antifolates. The index patient harbored a mixture of wild-type and resistant
pfdhfr
and
pfdhps
alleles upon initial presentation. During his second malaria episode, he harbored only resistant parasites, with the haplotypes IRNI (codons 51, 59, 108, and 164) and SGEAA (codons 436, 437, 540, 581, and 613) at these two loci, respectively. Analysis of isolates from 44 other patients showed that the
pfdhfr
haplotype IRNI was common (found in 81% of cases). The SGEAA haplotype of
pfdhps
was uncommon (found only in eight cases of East African origin [17%]). A previously undescribed mutation, I431V, was observed for seven cases of Nigerian origin, occurring as one of two haplotypes, VAGKGS or VAGKAA. The presence of this mutation was also confirmed in isolates of Nigerian origin from the United Kingdom Malaria Reference Laboratory. The presence of the
pfdhps
haplotype SGEAA in
P. falciparum
parasites of East African origin appears to compromise the efficacy of treatment regimens that include SP as a means to prevent recrudescence. Parasites with novel
pfdhps
haplotypes are circulating in West Africa. The response of these parasites to chemotherapy needs to be evaluated.
Structural Basis of APH(3′)-IIIa-Mediated Resistance to N1-Substituted Aminoglycoside Antibiotics
Authors: Fong Desiree H. , Berghuis Albert M.
Published: May 2009

Butirosin is unique among the naturally occurring aminoglycosides, having a substituted amino group at position 1 (N1) of the 2-deoxystreptamine ring with an (
S
)-4-amino-2-hydroxybutyrate (AHB) group. While bacterial resistance to aminoglycosides can be ascribed chiefly to drug inactivation by plasmid-encoded aminoglycoside-modifying enzymes, the presence of an AHB group protects the aminoglycoside from binding to many resistance enzymes, and hence, the antibiotic retains its bactericidal properties. Consequently, several semisynthetic N1-substituted aminoglycosides, such as amikacin, isepamicin, and netilmicin, were developed. Unfortunately, butirosin, amikacin, and isepamicin are not resistant to inactivation by 3′-aminoglycoside
O
-phosphotransferase type IIIa [APH(3′)-IIIa]. We report here the crystal structure of APH(3′)-IIIa in complex with an ATP analog, AMPPNP [adenosine 5′-(β,γ-imido)triphosphate], and butirosin A to 2.4-Å resolution. The structure shows that butirosin A binds to the enzyme in a manner analogous to other 4,5-disubstituted aminoglycosides, and the flexible antibiotic-binding loop is key to the accommodation of structurally diverse substrates. Based on the crystal structure, we have also constructed a model of APH(3′)-IIIa in complex with amikacin, a commonly used semisynthetic N1-substituted 4,6-disubstituted aminoglycoside. Together, these results suggest a strategy to further derivatize the AHB group in order to generate new aminoglycoside derivatives that can elude inactivation by resistance enzymes while maintaining their ability to bind to the ribosomal A site.
Antiretroviral Drug Resistance Surveillance among Treatment-Naive Human Immunodeficiency Virus Type 1-Infected Individuals in Angola: Evidence for Low Level of Transmitted Drug Resistance
Authors: Bártolo Inês , Rocha Cheila , Bartolomeu José , Gama António , Fonseca Marlene , Mendes Ana , Cristina Filipa , Thamm Sven , Epalanga Marta , Silva Patrícia Cavaco , Taveira Nuno
Published: May 2009

The prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola.
Pyrazolopyrimidinediones Are Selective Agents for
Helicobacter pylori
That Suppress Growth through Inhibition of Glutamate Racemase (MurI)
Authors: de Jonge B. L. M. , Kutschke A. , Uria-Nickelsen M. , Kamp H. D. , Mills S. D.
Published: May 2009

Pyrazolopyrimidinediones are a novel series of compounds that inhibit growth of
Helicobacter pylori
specifically. Using a variety of methods, advanced analogues were shown to suppress the growth of
H. pylori
through the inhibition of glutamate racemase, an essential enzyme in peptidoglycan biosynthesis. The high degree of selectivity of the series for
H. pylori
makes these compounds attractive candidates for novel
H. pylori
-selective therapy.
Effect of Rifampin, a Potent Inducer of Drug-Metabolizing Enzymes, on the Pharmacokinetics of Raltegravir
Authors: Wenning Larissa A. , Hanley William D. , Brainard Diana M. , Petry Amelia S. , Ghosh Kalyan , Jin Bo , Mangin Eric , Marbury Thomas C. , Berg Jolene K. , Chodakewitz Jeffrey A. , Stone Julie A. , Gottesdiener Keith M. , Wagner John A. , Iwamoto Marian
Published: May 2009

Raltegravir is a human immunodeficiency virus type 1 integrase strand transfer inhibitor that is metabolized by glucuronidation via UGT1A1 and may be affected by inducers of UGT1A1, such as rifampin (rifampicin). Two pharmacokinetic studies were performed in healthy subjects: study 1 examined the effect of administration of 600-mg rifampin once daily on the pharmacokinetics of a single dose of 400-mg raltegravir, and study 2 examined the effect of 600-mg rifampin once daily on the pharmacokinetics of 800-mg raltegravir twice daily compared to 400-mg raltegravir twice daily without rifampin. Raltegravir coadministered with rifampin resulted in lower plasma raltegravir concentrations: in study 1, the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) for the plasma raltegravir concentration determined 12 h postdose (
C
12
), area under the concentration-time curve from 0 h to ∞ (AUC
0-∞
), and maximum concentration of drug in plasma (
C
max
) (400-mg raltegravir plus rifampin/400-mg raltegravir) were 0.39 (0.30, 0.51), 0.60 (0.39, 0.91), and 0.62 (0.37, 1.04), respectively. In study 2, the GMRs and 90% CIs for raltegravir
C
12
, AUC
0-12
, and
C
max
(800-mg raltegravir plus rifampin/400-mg raltegravir) were 0.47 (0.36, 0.61), 1.27 (0.94, 1.71), and 1.62 (1.12, 2.33), respectively. Doubling the raltegravir dose to 800 mg when coadministered with rifampin therefore compensates for the effect of rifampin on raltegravir exposure (AUC
0-12
) but does not overcome the effect of rifampin on raltegravir trough concentrations (
C
12
). Coadministration of rifampin and raltegravir is not contraindicated; however, caution should be used, since raltegravir trough concentrations in the presence of rifampin are likely to be at the lower limit of clinical experience.
Influence of the Cytochrome P450 2B6 Genotype on Population Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus Patients
Authors: Cabrera Salvador E. , Santos Dolores , Valverde María P. , Domínguez-Gil Alfonso , González Francisco , Luna Guillermo , García María J.
Published: May 2009

A population pharmacokinetic model for efavirenz has been developed from therapeutic drug monitoring data in human immunodeficiency virus (HIV)-positive patients by using a nonlinear mixed-effect model. The efavirenz plasma concentrations (n= 375) of 131 patients were analyzed using high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were estimated according to a one-compartment model. The effects of sex, age, total body weight, height, body mass index, and HIV treatment were analyzed. In a subgroup of 32 patients, genetic polymorphisms of the cytochrome P450 2B6 gene (CYP2B6),CYP3A4, andMDR1were also investigated. Efavirenz oral clearance and the apparent volume of distribution were 9.50 liters/h and 311 liters, respectively. The model included only the effect ofCYP2B6polymorphisms on efavirenz clearance; this covariate reduced the intersubject variability of clearance by about 27%. Patients showing G/T and T/TCYP2B6polymorphisms exhibited efavirenz clearances that were about 50% and 75% lower than those observed in the patients without these polymorphisms (G/G). Accordingly, to obtain EFV steady-state concentrations within the therapeutic range (1 to 4 mg/liter), it would be advisable to implement a gradual reduction in dose to 400 or 200 mg/day for patients that are intermediate or poor metabolizers, respectively. However, the remaining interindividual variability observed in the pharmacokinetic parameters of the model highlights the need for dose individualization to avoid inadequate exposure to efavirenz and suggests that these recommended doses be used with caution and confirmed by therapeutic drug monitoring and clinical efficacy. The population model can be implemented in pharmacokinetic clinical software for dosage optimization by using the Bayesian approach.
Secretion of GOB Metallo-β-Lactamase in
Escherichia coli
Depends Strictly on the Cooperation between the Cytoplasmic DnaK Chaperone System and the Sec Machinery: Completion of Folding and Zn(II) Ion Acquisition Occur in the Bacterial Periplasm
Authors: Morán-Barrio Jorgelina , Limansky Adriana S. , Viale Alejandro M.
Published: May 2009

Metallo-β-lactamases (MβLs) are zinc-dependent enzymes produced by many clinically relevant gram-negative pathogens that can hydrolyze most β-lactam antibiotics. MβLs are synthesized in the bacterial cytoplasm as precursors and are secreted into the periplasm. Here, we report that the biogenesis process of the recently characterized MβL GOB-18 demands cooperation between a main chaperone system of the bacterial cytoplasm, DnaK, and the Sec secretion machinery. Using the expression of the complete
gob-18
gene from the gram-negative opportunistic pathogen
Elizabethkingia meningoseptica
in
Escherichia coli
as a model system, we found that the precursor of this metalloenzyme is secreted by the Sec pathway and reduces cell susceptibility to different β-lactam antibiotics. Moreover, acting with different J proteins such as cytoplasmic DnaJ and membrane-associated DjlA as cochaperones, DnaK plays an essential role in the cytoplasmic transit of the GOB-18 precursor to the Sec translocon. Our studies also revealed a less relevant role, that of assisting in GOB-18 secretion, for trigger factor, while no significant functions were found for other main cytoplasmic chaperones such as SecB or GroEL/ES. The overall findings indicate that the biogenesis of GOB-18 involves cytoplasmic interaction of the precursor protein mainly with DnaK, secretion by the Sec system, and final folding and incorporation of Zn(II) ions into the bacterial periplasm.
Lipopolysaccharide-Trap-Fc, a Multifunctional Agent To Battle Gram-Negative Bacteria
Authors: Groß Philipp , Brandl Katharina , Dierkes Christine , Schölmerich Jürgen , Salzberger Bernd , Glück Thomas , Falk Werner
Published: May 2009

The family of Toll-like receptors (TLRs) plays a pivotal role in host defense against pathogens. However, overstimulation of these receptors may lead to uncontrolled general inflammation and eventually to systemic organ dysfunction or failure. With the intent to control overwhelming inflammation during gram-negative bacterial sepsis, we constructed soluble fusion proteins of the lipopolysaccharide (LPS)-receptor complex to modulate TLR signaling in multiple ways. The extracellular domain of mouse TLR4 and mouse myeloid differentiation factor 2 (MD-2) fusions (LPS-Trap) were linked to human immunoglobulin G Fc domains (LPS-Trap-Fc). In addition to the ability to bind LPS or gram-negative bacteria and to inhibit interleukin-6 secretion of monocytic cells after LPS treatment, LPS-Trap-Fc was able to opsonize fluorescentEscherichia coliparticles. This led to enhancement of phagocytosis by monocytic cells which was strictly dependent on the presence of the Fc region. Moreover, only LPS-Trap-Fc- and not LPS-Trap-coated bacteria were sensitized to complement killing. Therefore, LPS-Trap-Fc not only neutralizes LPS but also, after binding to bacteria, enhances phagocytosis and complement-mediated killing and could thus act as a multifunctional agent to fight gram-negative bacteria in vivo.
Transcriptional and Translational Analysis of Biofilm Determinants of
Aggregatibacter actinomycetemcomitans
in Response to Environmental Perturbation
Authors: Amarasinghe Jayaleka J. , Scannapieco Frank A. , Haase Elaine M.
Published: May 2009

Fimbriae, lipopolysaccharide (LPS), and extracellular polymeric substance (EPS) all contribute to biofilm formation by the periodontopathogen
Aggregatibacter actinomycetemcomitans
. To understand how individual biofilm determinants respond to changing environmental conditions, the transcription of genes responsible for fimbria, LPS, and EPS production, as well as the translation of these components, was determined in rough (Rv) and isogenic smooth (Sv) variants of
A. actinomycetemcomitans
cultured in half-strength and full-strength culture medium under anaerobic or aerobic conditions, and in iron-supplemented and iron-chelated medium. The transcription of
tadV
(fimbrial assembly),
pgaC
(extracellular polysaccharide synthesis), and
orf8
or
rmlB
(lipopolysaccharide synthesis) was measured by real-time PCR. The amounts of fimbriae, LPS, and EPS were also estimated from stained sodium dodecyl sulfate-polyacrylamide gels and verified by Western blotting and enzyme-linked immunoadsorbent assay using specific antibodies. Each gene was significantly upregulated in the Rv compared to in the Sv. The transcription of fimbrial, LPS, and EPS genes in the Rv was increased approximately twofold in cells cultured in full-strength medium under anaerobic conditions compared to that in cells cultured under aerobic conditions. Under anaerobic conditions, the transcription of fimbrial and EPS enzymes was elevated in both Rv and Sv cells cultured in half-strength medium, compared to that in full-strength medium. Iron chelation also increased the transcription and translation of all biofilm determinants compared to their expression with iron supplementation, yet the quantity of biofilm was not significantly changed by any environmental perturbation except iron limitation. Thus, anaerobic conditions, nutrient stress, and iron limitation each upregulate known biofilm determinants of
A. actinomycetemcomitans
to contribute to biofilm formation.
ace
, Which Encodes an Adhesin in
Enterococcus faecalis
, Is Regulated by Ers and Is Involved in Virulence
Authors: Lebreton Francois , Riboulet-Bisson Eliette , Serror Pascale , Sanguinetti Maurizio , Posteraro Brunella , Torelli Riccardo , Hartke Axel , Auffray Yanick , Giard Jean-Christophe
Published: May 2009

Enterococcus faecalis
is an opportunistic pathogen that causes numerous infectious diseases in humans and is a major agent of nosocomial infections. In this work, we showed that the recently identified transcriptional regulator Ers (PrfA like), known to be involved in the cellular metabolism and the virulence of
E. faecalis
, acts as a repressor of
ace
, which encodes a collagen-binding protein. We characterized the promoter region of
ace
, and transcriptional analysis by reverse transcription-quantitative PCR and mobility shift protein-DNA binding assays revealed that Ers directly regulates the expression of
ace
. Transcription of
ace
appeared to be induced by the presence of bile salts, probably via the deregulation of
ers
. Moreover, with an
ace
deletion mutant and the complemented strain and by using an insect (
Galleria mellonella
) virulence model, as well as in vivo-in vitro murine macrophage models, we demonstrated for the first time that Ace can be considered a virulence factor for
E. faecalis
. Furthermore, animal experiments revealed that Ace is also involved in urinary tract infection by
E. faecalis
.
Compartmental cross-talk in the regulation of light harvesting complex transcription under short-term light and temperature stress in Chlamydomonas reinhardtii
Authors: Humby Penny L. , Cunningham Michelle L. , Saunders Holly L. , Price Julie A. , Durnford Dion G.
Published: May 2009

Short-term light stress in Chlamydomonas leads to transient changes in light harvesting complex (LHC) transcription. This requires cross-talk between the plastid and nucleus to coordinate chloroplast function with nuclear transcription. None of the components of this signalling pathway have been identified although several sensor candidates have been proposed. To examine the regulation of nuclear photosynthetic gene expression, we constructed an LHC::Arylsulphatase (ARS) reporter system in Chlamydomonas reinhardtii allowing us to examine short-term regulatory changes on a fine scale. We modulated plastoquinone (PQ) redox state via photosynthetic inhibitors, changes in light and (or) temperature and found no evidence that either the PQ pool or QA redox state were directly involved in short-term retrograde signalling. Shifts in light level and (or) temperature indicated that LHC transcriptional activity is tightly coordinated to photosynthetic production. Transient switching between photoautotrophic and mixotrophic growth, plus the use of mitochondrial inhibitors indicated that nuclear photosynthetic gene expression is coupled to mitochondrial activity. These short-term effects on LHC transcription demonstrate an interdependence of photosynthetic production and mitochondrial activity, suggesting Chlamydomonas is able to respond to environmental changes by monitoring metabolite pools between the chloroplast and mitochondria and not in the chloroplast directly.
Quantifying the growth of arbuscular mycorrhizal fungi: usefulness of the fractal dimension
Authors: Juge Christine , Champagne Annie , Coughlan Andrew P. , Juge Nicolas , Parrott Lael , Piché Yves
Published: May 2009

The present study is, to the best of our knowledge, the first to investigate the use of the fractal dimension (FD) to quantify the growth and development of undisturbed, fully functional arbuscular mycorrhizal (AM) hyphae developing in vitro. The majority of the work focused on the model AM fungus Glomus intraradices DAOM 181602. The time course study and final measurements of an intact mature extraradical mycelium allowed us to compare the development of the mycelium and the FD value. The final FD value of 1.62 for the mature mycelium is similar to that obtained for highly branched root systems and tree crowns. The FD method was used to characterize the morphology of germinative and presymbiotic hyphae in the presence of stimulatory (strigolactone GR-24, 0.1 µmol·L–1and bisphenol A, 10 µmol·L–1) and inhibitory (NaCl, 80 mmol·L–1) molecules, and the extraradical phase in the presence of an inhibitory molecule (NaCl, 80 mmol·L–1). Where possible, results were compared with those obtained using the traditional grid-line (GL) technique. The FD approach allowed treatment effects to be accurately quantified, both in germinative and extraradical phases. In the second case, this technique provided a single quantitative value of extraradical hyphal growth that included runner hyphae (RH) networks, and fine-branching (FB) ramifications. This is in contrast to the GL technique, which provides a value for the estimation of RH, but which is not suitable for accurately measuring FB hyphae. Given the ease with which the FD values can be calculated, and the fact that this method can provide a single value for the quantification of extraradical hyphal growth and development, we suggest that this method is useful for in vitro studies. Furthermore under certain situations of germinative or presymbiotic growth, it may be used in concert with the GL method to provide a greater degree of information about hyphal morphology. The usefulness and limits of the FD method at different stages of the AM fungal growth cycle are discussed.
LOGARITHMICAL CURVATURE-CORRECTED VOLTAGE REFERENCES WITH IMPROVED TEMPERATURE BEHAVIOR
Authors: POPA COSMIN
Published: May 2009

Two voltage reference circuits will be presented. For the first circuit, the linear compensation of V GS (T) for an MOS transistor in subthreshold region will be realized using an original offset voltage follower block as PTAT voltage generator, with the advantages of reducing the silicon area and of increasing accuracy by replacing matched resistors with matched transistors. A new logarithmic curvature-correction technique will be implemented using an asymmetric differential amplifier for compensating the logarithmic temperature dependent term from V GS (T). Because of the operation in weak inversion of all MOS transistors, the circuit will have a very small current consumption, making it compatible with low-power low-voltage designs. The simulated temperature coefficient of the reference voltage for V DD = 2.5 V and a temperature range 0 < t < 30° C is 36.5 ppm/K, confirming the theoretical estimations. The variation of the reference voltage with respect to the supply voltage is 1.5 mV/V for 2–4 V. The circuit current consumption is about 1 μA and the minimal supply voltage is 2 V. The main goal of the second proposed voltage reference is to improve the temperature behavior of a previous reported bipolar voltage reference, by replacing the bipolar transistors with MOS transistors working in weak inversion, with the advantage of obtaining the compatibility with CMOS technology. The new proposed curvature-correction technique will be based on the compensation of the nonlinear temperature dependence of the gate-source voltage for a subthreshold operated MOS transistor by a correction current obtained by taking the difference between two gate-source voltages for MOS transistors biased at drain currents with different temperature dependencies. The circuit is implemented in 0.35 μm CMOS technology. The SPICE simulation confirms the theoretical estimated results, reporting a temperature coefficient of 4.23 ppm/K for the commercial temperature range, 0 < t < 70° C and a small supply voltage, V DD = 2.5 V . The variation of the reference voltage with respect to the supply voltage is 0.9 mV/V for 2–4 V.
LOW POWER, LOW LATENCY, HIGH THROUGHPUT 16-BIT CSA ADDER USING NONCLOCKED PASS-TRANSISTOR LOGIC
Authors: SENTHILPARI C. , DIWAKAR K. , SINGH AJAY KUMAR
Published: May 2009

As the CMOS technology continues to scale to achieve higher performance, power dissipation and robustness to leakage and, process variations are becoming major obstacles for circuit design in the nanoscale technologies. Due to increased density of transistors in integrated circuits and higher frequencies of operation, power consumption, propagation delay, PDP, and area is reaching the lower limits. We have designed 16-bit adder circuit by Carry-Select Adder (CSA) using different pass-transistor logic. The adder cells are designed by DSCH3 CAD tools and layout are generated by Microwind 3 VLSI CAD tools. Using CSA technique, the power dissipation, PDP, area, transistor count, are calculated from the layout cell of proposed 16-bit adder for Ultra Deep Submicron feature size of 120, 90, 70, and 50 nm. The UDSM signal parameters are calculated such as signal to noise ratio (SNR), energy per instruction (EPI), Latency, and throughput using layout parameter analysis of BSIM 4. The simulated results show that the CPL is dominant in terms of power dissipation, propagation delay, PDP, and area among the other pass gate logics. Our CPL circuit dominates in terms of EPI, SNR, throughput, and latency in signal parameters analysis. The proposed CPL adder circuit is compared with reported results and found that our CPL circuit gives better performance.
LOW VOLTAGE LOW POWER FULLY DIFFERENTIAL BUFFER
Authors: STORNELLI VINCENZO
Published: May 2009

In this paper a useful CMOS fully-differential buffer topology is presented. The proposed solution, performing the common mode feedback operation, shows a rail-to-rail characteristic, so it is particularly suitable for low-voltage (± 0.75 V) low-power (< 400 μW) applications. The simulated results have shown excellent general performance, evaluated in terms of suitable figures of merit.
CRITICAL BEHAVIOR IN AN EVOLUTIONARY ULTIMATUM GAME WITH SOCIAL STRUCTURE
Authors: EGUÍLUZ VÍCTOR M. , TESSONE CLAUDIO J.
Published: May 2009

Experimental studies have shown the ubiquity of altruistic behavior in human societies. The social structure is a fundamental ingredient to understand the degree of altruism displayed by the members of a society, in contrast to individual-based features, like for example age or gender, which have been shown not to be relevant to determine the level of altruistic behavior. We explore an evolutionary model aiming to delve how altruistic behavior is affected by social structure. We investigate the dynamics of interacting individuals playing the Ultimatum Game with their neighbors given by a social network of interaction. We show that a population self-organizes in a critical state where the degree of altruism depends on the topology characterizing the social structure. In general, individuals offering large shares but in turn accepting large shares, are removed from the population. In heterogeneous social networks, individuals offering intermediate shares are strongly selected in contrast to random homogeneous networks where a broad range of offers, below a critical one, is similarly present in the population.
FUZZY ARROW'S THEOREM
Authors: MORDESON JOHN N. , CLARK TERRY D.
Published: May 2009

In this paper, we prove a fuzzy version of Arrow's Theorem that contains the crisp version. We show that under our definitions, Arrow's Theorem remains intact even if levels of intensities of the players and levels of membership in the set of alternatives are considered.
FAIR CONSISTENCY EVALUATION FOR RECIPROCAL RELATIONS AND IN GROUP DECISION MAKING
Authors: FEDRIZZI MICHELE , BRUNELLI MATTEO
Published: May 2009

In decision-making processes, it often occurs that the decision maker is asked to pairwise compare alternatives. His/her judgements over a set of pairs of alternatives can be collected into a matrix and some relevant properties, for instance, consistency, can be estimated. Consistency is a desirable property which implies that all the pairwise comparisons respect a principle of transitivity. So far, many indices have been proposed to estimate consistency. Nevertheless, in this paper we argue that most of these indices do not fairly evaluate this property. Then, we introduce a new consistency evaluation method and we propose to use it in group decision making problems in order to fairly weigh the decision maker's preferences according to their consistency. In our analysis, we consider two families of pairwise comparison matrices: additively reciprocal pairwise comparison matrices and multiplicatively reciprocal pairwise comparison matrices.
DESIGN OF KNOWLEDGE DRIVEN INTERFACES IN CULTURAL CONTEXTS
Authors: VALTOLINA STEFANO
Published: May 2009

A major problem in developing interactive interfaces is how to guide users with respect to which queries they can ask. This is because users need to know what is possible to ask in a particular domain. This paper explores these issues in the context of cultural heritage (CH) environments. The effective presentation of CH information requires the application of sophisticated techniques from different areas, mainly human-computer interaction and knowledge management. In this kind of interactive applications users should adopt different accessing strategies independently of how the information is organized in the repositories. Thus, if the information domain is spread in different sources the user has to be able to operate in a transparent way independently of the data-structures of the archives. Moreover, the user would not be taken aback by a huge amount of data available, but the information has to be tailored according to the real user's interests. The proposed approach is based on the definition of relationships between the information cultural domain fitting the conceptual model of the cultural experts (represented by an appropriate knowledge base) and an information domain which can be understood by the machine (modeled by a domain ontology). The final system's infrastructure filters the richness of the data-sources to comply with the users' needs, tailoring the information according to their context of use. In this way the user can properly navigate through the heritage and create their own personalized thematic tour through a large number of information trails.
The Jurassic and Cretaceous bony fish record (Actinopterygii, Dipnoi) from Thailand
Authors: Cavin Lionel , Deesri Uthumporn , Suteethorn Varavudh
Published: May 2009

This first overview of the bony fish record from the Jurassic and Cretaceous continental deposits of Thailand reveals a significant diversity, with 16 taxa in four formations (the Khlong Min, Phu Kradung, Sao Khua and Khok Kruat Fms). Four of these taxa have already been diagnosed and described, and a couple of others are sufficiently well preserved to be diagnosed in the future. The other taxa are represented at present by fragmentary and isolated remains. The highest diversity is observed among ‘semionotids’, which occur in the four formations. Sinamiids are represented by at least three taxa that occur only in the Sao Khua and the Khok Kruat Formations. Pycnodont fishes are known by rare and isolated dentitions and teeth in the Khlong Min and Sao Khua Formations, and lungfishes referred to
Ferganoceratodus
occur in the Khlong Min and the Phu Kradung Formations. The assemblages provide few palaeogeographical indications at present, except for evidence of relationships with China and Central Asia. However, it is expected than once the phylogenetic relationships of these taxa are resolved, we will be able to reconstruct precise palaeogeographical scenarios.
Turtle assemblages of the Khorat Group (Late Jurassic-Early Cretaceous) of NE Thailand and their palaeobiogeographical significance
Authors: Tong Haiyan , Claude Julien , Suteethorn Varavudh , Naksri Wilailuck , Buffetaut Eric
Published: May 2009

The turtle assemblages from the Khorat Group consist mainly of trionychoids. They include the primitive Trionychoidae
Basilochelys
and basal eucryptodiran turtles from the Phu Kradung Formation (?Late Jurassic); the adocid
Isanemys srisuki
, the carettochelyid
Kizylkumemys
sp. and undetermined Trionychoidea from the Sao Khua Formation (Early Cretaceous); and the carettochelyid
Kizylkumemys khoratensis
and the adocid
Shachemys
sp. from the Khok Kruat Formation (Aptian). Our study shows some faunal links between the turtle faunas from the Khorat Group and those from the peripheral regions of Asia during the time span of the Khorat Group. Thus the coastal regions of Asia, and more particularly SE Asia, may have been important places for the origin and early diversification of the trionychoids.
Khoratosuchus jintasakuli
gen. et sp. nov., an advanced neosuchian crocodyliform from the Early Cretaceous (Aptian-Albian) of NE Thailand
Authors: Lauprasert K. , Cuny G. , Thirakhupt K. , Suteethorn V.
Published: May 2009

A new slender-snouted neosuchian crocodyliform,
Khoratosuchus jintasakuli
gen. et sp. nov., is described from the late Early Cretaceous Khok Kruat Formation of NE Thailand. This discovery represents the youngest and most advanced Mesozoic crocodyliform known in Thailand on the basis of the following cranial features: the secondary choanae are relatively posterior and almost enclosed by the pterygoid; the lateral margin of the maxilla is relatively straight without lateral constrictions; the dorsal surface of the skull lacks ridges and fossae; maxillary teeth are homodontous; the anterior end of the jugal and prefrontal terminate at the same level. The specimen bears resemblances to Chinese and European derived neosuchians and suggests a close relationship between the late Early Cretaceous neosuchians of China, Europe and SE Asia.
A new skeleton of
Phuwiangosaurus sirindhornae
(Dinosauria, Sauropoda) from NE Thailand
Authors: Suteethorn S. , Le Loeuff J. , Buffetaut E. , Suteethorn V. , Talubmook C. , Chonglakmani C.
Published: May 2009

A new skeleton of a sauropod dinosaur has been discovered in the Early Cretaceous Sao Khua Formation at Ban Na Khrai in Changwat Kalasin (NE Thailand). All sauropod bones from Ban Na Khrai share all their characteristics with the type specimen of
Phuwiangosaurus sirindhornae
Martin, Buffetaut & Suteethorn 1994
. The 60% complete skeleton is very well preserved and includes cranial elements (a tooth, a frontal, a postorbital, a squamosal, both quadrates, and the braincase), whereas the type specimen is only 10% complete and consists of postcranial bones only. The material from Ban Na Khrai belongs to a single subadult individual of
Phuwiangosaurus
, as attested by the unfused neurocentral sutures of the vertebrae, which are firmly fused and larger in size in the holotypic specimen.
Bone histology and its implications for the life history and growth of the Early Cretaceous titanosaur
Phuwiangosaurus sirindhornae
Authors: Klein Nicole , Sander Martin , Suteethorn Varavudh
Published: May 2009

Bone histology is the most comprehensive way of obtaining data on growth and life history for dinosaurs. Humeri and femora of the basal titanosaur
Phuwiangosaurus sirindhornae
from the Early Cretaceous of Thailand were sampled by core drilling. The sample represents growth series with humeri ranging in size from 71.0 to 110.0 cm and femora ranging in size from 38.5 to 112.0 cm. The bone tissue is continuously growing laminar fibro-lamellar bone typical for virtually all sauropods. Several ontogenetic stages can be distinguished, and a general growth pattern is deduced on the basis of different-sized individuals. Humeri differ from femora in generally showing more remodelling by secondary osteons.