bluuebunny/crossref_metadata_2025 huggingface dataset:
Ammonium transport in the colonic crypt cell line, T84: role for Rhesus glycoproteins and NKCC1
Authors: Worrell Roger T. , Merk Lisa , Matthews Jeffrey B.
Published: November 2007

Although colonic lumen NH4+levels are high, 15–44 mM normal range in humans, relatively few studies have addressed the transport mechanisms for NH4+. More extensive studies have elucidated the transport of NH4+in the kidney collecting duct, which involves a number of transporter processes also present in the distal colon. Similar to NH4+secretion in the renal collecting duct, we show that the distal colon secretory model, T84 cell line, has the capacity to secrete NH4+and maintain an apical-to-basolateral NH4+gradient. NH4+transport in the secretory direction was supported by basolateral NH4+loading on NKCC1, Na+-K+-ATPase, and the NH4+transporter, RhBG. NH4+was transported on NKCC1 in T84 cells nearly as well as K+as determined by bumetanide-sensitive86Rb-uptake.86Rb-uptake and ouabain-sensitive current measurement indicated that NH4+is transported by Na+-K+-ATPase in these cells to an equal extent as K+. T84 cells expressed mRNA for the basolateral NH4+transporter RhBG and the apical NH4+transporter RhCG. Net NH4+transport in the secretory direction determined by14C-methylammonium (MA) uptake and flux occurred in T84 cells suggesting functional RhG protein activity. The occurrence of NH4+transport in the secretory direction within a colonic crypt cell model likely serves to minimize net absorption of NH4+because of surface cell NH4+absorption. These findings suggest that we rethink the present limited understanding of NH4+handling by the distal colon as being due solely to passive absorption.
Hepatocyte nuclear factor-4α promotes differentiation of intestinal epithelial cells in a coculture system
Authors: Lussier Carine R. , Babeu Jean-Philippe , Auclair Benoît A. , Perreault Nathalie , Boudreau François
Published: November 2007

Normal cellular models able to efficiently recapitulate intestinal epithelial cell differentiation in culture are not yet available. The aim of this work was to establish and genetically characterize a mesenchymal-epithelial coculture system to identify transcriptional regulators involved in this process. The deposition of rat intestinal epithelial cells on human intestinal mesenchymal cells led to the formation of clustered structures that expanded shortly after seeding. These structures were composed of polarized epithelial cells with brush borders and cell junction complexes. A rat GeneChip statistical analysis performed at different time points during this process identified hepatocyte nuclear factor-4α (HNF-4α) and hepatocyte nuclear factor-1α (HNF-1α) as being induced coincidently with the apparition of polarized epithelial structures. Stable introduction of HNF-4α in undifferentiated epithelial cells alone led to the rapid induction of HNF-1α and several intestinal-specific markers and metabolism-related genes for which mRNA was identified to be upregulated during epithelial differentiation. HNF-4α was capable to transactivate the calbindin 3 gene promoter, a process that was synergistically increased in the presence of HNF-1α. When HNF-4α-expressing cells were plated on mesenchymal cells, an epithelial monolayer formed rapidly with the apparition of dome structures that are characteristics of vectorial ion transport. Forced expression of HNF-1α alone did not result in dome structures formation. In sum, this novel coculture system functionally identified for the first time HNF-4α as an important modulator of intestinal epithelial differentiation and offers an innovative opportunity to investigate molecular mechanisms involved in this process.
Proteasome inhibition promotes regression of left ventricular hypertrophy
Authors: Stansfield William E. , Tang Ru-Hang , Moss Nancy C. , Baldwin Albert S. , Willis Monte S. , Selzman Craig H.
Published: November 2007

Current research in left ventricular hypertrophy (LVH) has largely focused on its progression and therapeutic mechanisms to prevent or slow its development. Few studies have centered on the regression or treatment of existing LVH. Nuclear factor-κB (NF-κB) is an inflammatory transcription factor that has been shown to be involved in LVH development. We hypothesized that proteasome-mediated NF-κB inhibition would prevent the development of LVH and promote its regression. A murine model of reversible hypertrophy was employed by administering isoproterenol (Iso) subcutaneously for 7–14 days. The proteasome inhibitor, PS-519, was delivered both concurrently and after Iso treatment. LVH was quantified by heart weight-to-body weight ratios, histology, transthoracic echocardiography, and hypertrophic gene expression. After 7 days of Iso treatment, all measures indicated successful development of LVH. Another group was treated for 7 days and then observed for an additional 7 days. This group experienced normalization of Iso-induced cell size, wall thickness, and β-myosin heavy chain expression. When administered concurrently, PS-519 prevented Iso-induced LVH at 7 days. Furthermore, when PS-519 was given to animals during the second week of continued Iso treatment, these animals also experienced regression of hypertrophy by several measures. The success of proteasome inhibition in preventing LVH development and in promoting LVH regression, even in the face of continued hypertrophic stimulation, demonstrates its potential use as a clinically accessible strategy for treating patients with a variety of LVH-associated cardiomyopathies.
Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance
Authors: Subudhi Andrew W. , Lorenz Matthew C. , Fulco Charles S. , Roach Robert C.
Published: November 2007

We sought to describe cerebrovascular responses to incremental exercise and test the hypothesis that changes in cerebral oxygenation influence maximal performance. Eleven men cycled in three conditions: 1) sea level (SL); 2) acute hypoxia [AH; hypobaric chamber, inspired Po2(PiO2) 86 Torr]; and 3) chronic hypoxia [CH; 4,300 m, PiO286 Torr]. At maximal work rate (Ẇmax), fraction of inspired oxygen (FiO2) was surreptitiously increased to 0.60, while subjects were encouraged to continue pedaling. Changes in cerebral (frontal lobe) (COX) and muscle (vastus lateralis) oxygenation (MOX) (near infrared spectroscopy), middle cerebral artery blood flow velocity (MCA Vmean; transcranial Doppler), and end-tidal Pco2(PetCO2) were analyzed across %Ẇmax(significance at P < 0.05). At SL, PetCO2, MCA Vmean, and COXfell as work rate rose from 75 to 100% Ẇmax. During AH, PetCO2and MCA Vmeandeclined from 50 to 100% Ẇmax, while COXfell from rest. With CH, PetCO2and COXdropped throughout exercise, while MCA Vmeanfell only from 75 to 100% Ẇmax. MOXfell from rest to 75% Ẇmaxat SL and AH and throughout exercise in CH. The magnitude of fall in COX, but not MOX, was different between conditions (CH > AH > SL). FiO20.60 at Ẇmaxdid not prolong exercise at SL, yet allowed subjects to continue for 96 ± 61 s in AH and 162 ± 90 s in CH. During FiO20.60, COXrose and MOXremained constant as work rate increased. Thus cerebral hypoxia appeared to impose a limit to maximal exercise during hypobaric hypoxia (PiO286 Torr), since its reversal was associated with improved performance.
Cholinergic location of δ-opioid receptors in canine atria and SA node
Authors: Deo Shekhar H. , Barlow Matthew A. , Gonzalez Leticia , Yoshishige Darice , Caffrey James L.
Published: November 2007

δ-Opioid receptors (DORs) are associated with ischemic preconditioning and vagal transmission in the sinoatrial (SA) node and atria. Although functional studies suggested that DORs are prejunctional on parasympathetic nerve terminals, their precise location remains unconfirmed. DORs were colocalized in tissue slices and synaptosomes from the canine right atrium and SA node along with cholinergic and adrenergic markers, vesicular acetylcholine transporter (VAChT), and tyrosine hydroxylase (TH). Synapsin I immunofluorescence verified the neural character of tissue structures and isolated synaptosomes. Acetylcholine and norepinephrine measurements suggested the presence of both cholinergic and adrenergic synaptosomes. Fluorescent analysis of VAChT and TH signals indicated that >80% of the synapsin-positive synaptosomes were of cholinergic origin and <8% were adrenergic. DORs colocalized 75–85% with synapsin in tissue slices from both atria and SA node. The colocalization was equally strong (85%) for nodal synaptosomes but less so for atrial synaptosomes (57%). Colocalization between DOR and VAChT was 75–85% regardless of the source. Overlap between DOR and TH was uniformly low, ranging from 8% to 17%. Western blots with synaptosomal extracts confirmed two DOR-positive bands at molecular masses corresponding to those reported for DOR monomers and dimers. The abundance of DOR was greater in nodal synaptosomes than in atrial synaptosomes, largely attributable to a greater abundance of monomers in the SA node. The abundant nodal and atrial DORs predominantly associated with cholinergic nerve terminals support the hypothesis that prejunctional DORs regulate vagal transmission locally within the heart.
Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria
Authors: Celie J. W. A. M. , Reijmers R. M. , Slot E. M. , Beelen R. H. J. , Spaargaren M. , ter Wee P. M. , Florquin S. , van den Born J.
Published: November 2007

Heparan sulfate proteoglycans (HSPGs) are well known for their proposed role in glomerular filtration. In addition, HSPGs can bind the leukocyte adhesion molecule l-selectin and chemokines, suggesting a role in inflammation. We examined a panel of biopsies representing different human primary kidney diseases for l-selectin and monocyte chemoattractant protein-1 (MCP-1) binding. In various renal diseases, l-selectin and MCP-1 binding to interstitial perivascular matrix HSPGs is increased, which is significantly associated with leukocyte influx. In proteinuric diseases, including membranous glomerulopathy, minimal change disease, but also IgA nephropathy and lupus nephritis, increased binding of l-selectin and MCP-1 to tubular epithelial cell (TEC) HSPGs is observed, which colocalizes with increased basolateral syndecan-1 and anti-heparan sulfate 10E4 staining. Short-hairpin RNA-mediated silencing demonstrates that syndecan-1 on TECs indeed mediates l-Selectin binding. Increased TEC expression of IL-8 in biopsies of proteinuric patients suggests that the increase in luminal protein may activate TECs to increase expression of l-selectin and MCP-1 binding syndecan-1. Strikingly, urinary syndecan-1 from proteinuric patients is less capable of binding l-selectin compared with urinary syndecan-1 from healthy controls, although syndecan-1 concentrations are similar in both groups. Together, our data show pronounced tubulointerstitial HSPG alterations in primary kidney disease, which may affect the inflammatory response.
Does Reorganization in the Cuneate Nucleus Following Neonatal Forelimb Amputation Influence Development of Anomalous Circuits Within the Somatosensory Cortex?
Authors: Lane Richard D. , Pluto Charles P. , Kenmuir Cynthia L. , Chiaia Nicolas L. , Mooney Richard D.
Published: November 2007

Neonatal forelimb amputation in rats produces sprouting of sciatic nerve afferent fibers into the cuneate nucleus (CN) and results in 40% of individual CN neurons expressing both forelimb-stump and hindlimb receptive fields. The forelimb-stump region of primary somatosensory cortex (S-I) of these rats contains neurons in layer IV that express both stump and hindlimb receptive fields. However, the source of the aberrant input is the S-I hindlimb region conveyed to the S-I forelimb-stump region via intracortical projections. Although the reorganization in S-I reflects changes in cortical circuitry, it is possible that these in turn are dependent on the CN reorganization. The present study was designed to directly test whether the sprouting of sciatic afferents into the CN is required for expression of the hindlimb inputs in the S-I forelimb-stump field. To inhibit sprouting, neurotrophin-3 (NT-3) was applied to the cut nerves following amputation. At P60 or older, NT-3-treated rats showed minimal sciatic nerve fibers in the CN. Multiunit electrophysiological recordings in the CN of NT-3-treated, amputated rats revealed 6.3% of sites were both stump/hindlimb responsive, compared with 30.5% in saline-treated amputated animals. Evaluation of the S-I following GABA receptor blockade, revealed that the percentage of hindlimb responsive sites in the stump representation of the NT-3-treated rats (34.2%) was not significantly different from that in saline-treated rats (31.5%). These results indicate that brain stem reorganization in the form of sprouting of sciatic afferents into the CN is not necessary for development of anomalous hindlimb receptive fields within the S-I forelimb/stump region.
Saccade Preparation Signals in the Human Frontal and Parietal Cortices
Authors: Curtis Clayton E. , Connolly Jason D.
Published: November 2007

Our ability to prepare an action in advance allows us to respond to our environment quickly, accurately, and flexibly. Here, we used event-related functional MRI to measure human brain activity while subjects maintained an active state of preparedness. At the beginning of each trial, subjects were instructed to prepare a pro- or antisaccade to a visual cue that was continually present during a long and variable preparation interval, but to defer the saccade's execution until a go signal. The deferred saccade task eliminated the mnemonic component inherent in memory-guided saccade tasks and placed the emphasis entirely on advance motor preparation. During the delay while subjects were in an active state of motor preparedness, the blood oxygen level–dependent signal in the frontal cortex showed 1) a sustained elevation throughout the preparation interval; 2) a linear increase with increasing delay length; 3) a bias for contra- rather than ipsiversive movements; 4) greater activity when the specific metrics of the planned saccade were known compared with when they were not; and 5) increased activity when the saccade was directed toward an internal versus an external representation (i.e., anticue location). These findings support the hypothesis that both the human frontal and parietal cortices are involved in the spatial selection and preparation of saccades.
Motor Control of Aimed Limb Movements in an Insect
Authors: Page Keri L. , Zakotnik Jure , Dürr Volker , Matheson Thomas
Published: November 2007

Limb movements that are aimed toward tactile stimuli of the body provide a powerful paradigm with which to study the transformation of motor activity into context-dependent action. We relate the activity of excitatory motor neurons of the locust femoro-tibial joint to the consequent kinematics of hind leg movements made during aimed scratching. There is posture-dependence of motor neuron activity, which is stronger in large amplitude (putative fast) than in small (putative slow and intermediate) motor neurons. We relate this posture dependency to biomechanical aspects of the musculo-skeletal system and explain the occurrence of passive tibial movements that occur in the absence of agonistic motor activity. There is little recorded co-activation of antagonistic tibial extensor and flexor motor neurons, and there is differential recruitment of proximal and distal flexor motor neurons. Large-amplitude motor neurons are often recruited soon after a switch in joint movement direction. Motor bursts containing large-amplitude spikes exhibit high spike rates of small-amplitude motor neurons. The fast extensor tibiae neuron, when recruited, exhibits a pattern of activity quite different to that seen during kicking, jumping, or righting: there is no co-activation of flexor motor neurons and no full tibial flexion. Changes in femoro-tibial joint angle and angular velocity are most strongly dependent on variations in the number of motor neuron spikes and the duration of motor bursts rather than on firing frequency. Our data demonstrate how aimed scratching movements result from interactions between biomechanical features of the musculo-skeletal system and patterns of motor neuron recruitment.
Maintaining Grip: Anticipatory and Reactive EEG Responses to Load Perturbations
Authors: Kourtis D. , Kwok H. F. , Roach N. , Wing A. M. , Praamstra P.
Published: November 2007

Previous behavioral work has shown the existence of both anticipatory and reactive grip force responses to predictable load perturbations, but how the brain implements anticipatory control remains unclear. Here we recorded electroencephalographs while participants were subjected to predictable and unpredictable external load perturbations. Participants used precision grip to maintain the position of an object perturbed by load force pulses. The load perturbations were either distributed randomly over an interval 700- to 4,300-ms (unpredictable condition) or they were periodic with interval 2,000 ms (predictable condition). Preparation for the predictable load perturbation was manifested in slow preparatory brain potentials and in electromyographic and force signals recorded concurrently. Preparation modulated the long-latency reflex elicited by load perturbations with a higher amplitude reflex response for unpredictable compared with predictable perturbations. Importantly, this modulation was also reflected in the amplitude of sensorimotor cortex potentials just preceding the long-latency reflex. Together, these results support a transcortical pathway for the long-latency reflex and a central modulation of the reflex grip force response.
Recommendations for the Measurement of FIV1 Values in Chronic Obstructive Pulmonary Disease
Authors: Visser Frank J. , Ramlal Sunil , Dekhuijzen P.N. Richard , Heijdra Yvonne F.
Published: November 2007

Background: In contrast to static inspiratory parameters such as vital capacity and inspiratory capacity, information on forced inspiratory volume in 1 s (FIV1) in patients with chronic obstructive pulmonary disease (COPD) is limited. Objectives: It was the aim of this study to investigate the influence of the preceding expiratory manoeuvre and the optimal number of manoeuvres on FIV1 values. Methods: In 169 patients with COPD, FIV1 manoeuvres were performed after a forced (FIV1-Fe) and a slow (FIV1-Se) expiration. To investigate the optimal number of the FIV1-Se manoeuvres, 8 attempts were performed. Results: The variability of FIV1-Fe was greater than that of FIV1-Se. The mean difference between FIV1-Se and FIV1-Fe was 0.21 litres (p < 0.01) and dependent on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The higher the GOLD stage, the greater the difference between the 2 techniques. The correlation coefficient between FIV1-Se and FIV1-Fe was high (r = 0.89, p = 0.01), but there was a poor agreement between these parameters (limits of agreement –0.52 to 0.94 litres). Five manoeuvres were needed to obtain an optimal FIV1-Se. There was no association with the GOLD stage. Conclusions: In COPD patients, FIV1-Se are less variable than FIV1-Fe, the agreement between the 2 manoeuvres is poor, and at least 5 FIV1-Se manoeuvres are needed to get an acceptable FIV1. This holds for all GOLD stages.
Antiinflammatory and Antiatherogenic Effects of the NF-κB Inhibitor Acetyl-11-Keto-β-Boswellic Acid in LPS-Challenged ApoE
−/−
Mice
Authors: Cuaz-Pérolin Clarisse , Billiet Ludivine , Baugé Eric , Copin Corinne , Scott-Algara Daniel , Genze Felicitas , Büchele Berhold , Syrovets Tatiana , Simmet Thomas , Rouis Mustapha
Published: November 2007

Objective—

In this article, we studied the effect of acetyl-11-keto-β-boswellic acid (AKβBA), a natural inhibitor of the proinflammatory transcription factor NF-κB on the development of atherosclerotic lesions in apolipoprotein E–deficient (apoE
−/−
) mice.

Methods and Results—

Atherosclerotic lesions were induced by weekly LPS injection in apoE
−/−
mice. LPS alone increased atherosclerotic lesion size by ≈100%, and treatment with AKβBA significantly reduced it by ≈50%. Moreover, the activity of NF-κB was also reduced in the atherosclerotic plaques of LPS-injected apoE
−/−
mice treated with AKβBA. As a consequence, AKβBA treatment led to a significant downregulation of several NF-κB–dependent genes such as MCP-1, MCP-3, IL-1α, MIP-2, VEGF, and TF. By contrast, AKβBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKβBA potently inhibited the IκB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IκBα and inhibition of p65/NF-κB activation. Comparable AKβBA-mediated inhibition was also observed in LPS-stimulated human macrophages.

Conclusion—

The inhibition of NF-κB activity by plant resins from species of the
Boswellia
family might represent an alternative for classical medicine treatments for chronic inflammatory diseases such as atherosclerosis.
(Arterioscler Thromb Vasc Biol.
2008;28:272-277)
Spontaneous Atherosclerosis in Aged Lipoprotein Lipase–Deficient Mice With Severe Hypertriglyceridemia on a Normal Chow Diet
Authors: Zhang Xiaohong , Qi Rong , Xian Xunde , Yang Fei , Blackstein Michael , Deng Xuming , Fan Jianglin , Ross Colin , Karasinska Joanna , Hayden Michael R. , Liu George
Published: November 2007

Large-scale epidemiological studies have revealed a strong association between hypertriglyceridemia and coronary arteriosclerotic disease. However, there are conflicting reports whether the severe hypertriglyceridemia caused by lipoprotein lipase (LPL) deficiency is pro- or antiatherogenic. To determine the effect of LPL deficiency on atherosclerosis, we pursued long-term observation of the development of atherosclerotic lesions in an LPL gene deficient mouse model. At 4 months of age, homozygous LPL-deficient mice exhibited severe hypertriglyceridemia but no signs of aortic atherosclerotic lesions. At >15 months of age, these mice developed foam cell-rich atherosclerotic lesions at the aortic root, whereas wild-type and heterozygous mice were lesion-free at the same age. Further investigation revealed that plasma malondialdehyde levels in >15-month-old LPL-deficient mice were significantly higher than those of heterozygous and wild-type mice. Electron spin resonance analysis showed a marked increase in oxidative susceptibility of chylomicrons from the aged LPL-deficient mice. Incubation of chylomicrons from >15-month-old LPL-deficient mice with cultured human umbilical vein endothelial cells showed significantly increased upregulation of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, markers of enhanced endothelial activation, and enhanced adherence of human THP-1 mononuclear cells. These results clearly demonstrate the occurrence of spontaneous atherosclerosis in aged LPL-deficient mice mediated by the oxidation of chylomicrons and the activation of vascular endothelial cells.
Responses of Endothelial Cell and Astrocyte Matrix-Integrin Receptors to Ischemia Mimic Those Observed in the Neurovascular Unit
Authors: Milner Richard , Hung Stephanie , Wang Xiaoyun , Berg Greta I. , Spatz Maria , del Zoppo Gregory J.
Published: November 2007

Background and Purpose—

Apposition of endothelial cells and astrocyte foot processes to the basal lamina matrix is postulated to underlie the cerebral microvessel permeability barrier. Focal cerebral ischemia induces rapid loss of select matrix-binding integrins from both cell compartments in the nonhuman primate. This study is the first to examine the conditions underlying integrin loss from these cell-types during ischemia in vitro and their relation to the changes in vivo.

Methods—

The impact of normoxia or standardized oxygen-glucose deprivation on integrin expression by murine primary cerebral endothelial cells and astrocytes grown on matrix substrates (collagen IV, laminin, and perlecan) of the basal lamina were quantitatively assessed by flow cytometry.

Results—

Endothelial cell expression of the β1 and α5 subunits significantly increased on all matrix ligands, whereas astrocytes displayed modest significant decreases in α5 and α6 subunits. Oxygen-glucose deprivation produced a further significant increase in subunit β1 expression by both cell types, but a clear decrease in both α1 and α6 subunits by murine astrocytes.

Conclusions—

Ischemia in vitro significantly increased endothelial cell β1 expression, which is consistent with the increase in β1 transcription by microvessels peripheral to the ischemic core. The loss of α1 and α6 integrins from murine astrocytes is identical to that seen in the nonhuman primate in vivo. These findings establish both isolated murine cerebral endothelial cells and astrocytes as potential integrin response cognates of microvascular cells of the neurovascular unit in primates, and allow determination of the mechanisms of their changes to ischemia.
Essential Work of Fracture and Acoustic Emission Study on TPNR Composites Reinforced by Kenaf Fiber
Authors: Anuar H. , Ahmad S.H. , Rasid R. , Surip S.N. , Czigany T. , Romhany G.
Published: November 2007

Kenaf fiber (KF) based thermoplastic natural rubber (TPNR) composite was produced by melt blending with polypropylene (PP). Kenaf fiber (15% by volume) and TPNR were mixed in as Haake 600p internal mixer. The fracture behavior of the TPNR matrix and of TPNR—kenaf (with and without maleic anhydride grafted polypropylene, MAPP) composites was evaluated using the essential work of fracture (EWF) method and double edge notched tensile (DENT) specimens. Various ligament lengths were employed ranging from 4 to 12 mm. The strain rate was fixed at 2 mm/min. The specific work of fracture (we) and plastic work (βwp) showed the highest energy for TPNR that corresponds to its ductility and allows the application of the EWF approach. It was found that the presence of kenaf fibers and MAPP reduced the toughness of TPNR and changed the ductile fracture to brittle behavior. SEM observation revealed that energy absorption mechanisms include matrix deformation, fiber pullout, and fiber breakage. Acoustic emission (AE) was employed to analyze the failure processes further. The signals emitted by composites were substantially higher than that of the TPNR matrix, reflecting that also the failure mechanisms were affected by the fibers incorporated.
Impact Analysis of Fiber-reinforced Composites Based on Elasto-plastic Constitutive Law
Authors: Joo Ki Ho , Ryou Hansun , Chung Kwansoo , Kang Tae Jin
Published: November 2007

Impact analysis of 3D braided composites and laminated plane woven fabric composites was performed using the elasto-plastic constitutive law to describe the nonlinear, anisotropic and asymmetric properties of fiber-reinforced composites. As for the yield criterion, the modified Drucker—Prager yield criterion was utilized to represent the anisotropic and asymmetric properties, while the anisotropic hardening was described based on the kinematic hardening with the anisotropic evolution of the back-stress. Experiments to obtain the material parameters of the proposed constitutive law were also carried out based on uni-axial tension and compression tests for fiber-reinforced composites. Then, the proposed constitutive law was implemented into a finite element code and was verified by comparing the finite element simulation of the impact tests with experiments. In addition, impact performance of the braided composites and laminated composites was also compared with each other.
Television and the European Public Sphere
Authors: Gripsrud Jostein
Published: November 2007

■ The European Union would like European citizens to be more involved in its political processes and to cast off its `democratic deficit`. A functioning European public sphere has been seen as both a solution and an instrument for producing a European identity that might motivate more participation. The main question discussed in this article is what the medium of television can contribute and already has contributed to the construction and existence of a European public sphere. On the way to a (preliminary) conclusion, the article suggests definitions and understandings of the key terms involved and sketches an overview of transnational television in Europe. It then suggests that while the EU may challenge the nationalist idea that a polity must also be a `complete' cultural community, and some seem to think a polity can do without any cultural community to speak of, one should rather think of the EU as a political project that gradually, over time, will add a `European' layer to the identities of Europeans — not least due to the sort of everyday cultural community that television has contributed to since the early 1950s. ■
A pilot study to determine mercury exposure through vapor and bound to PM10 in a dental school environment
Authors: Gioda Adriana , Hanke Gilberto , Elias-Boneta Augusto , Jiménez-Velez Braulio
Published: November 2007

Mercury (Hg) is widely used in the dental working environment, exposing dental practitioners and assistants to potentially toxic Hg vapors. Concentrations of Hg in vapor and in particulate matter (PM10) were measured in the Dental Simulation Laboratory (DSL) and in the Dental Clinic (DC) at the School of Dentistry, University of Puerto Rico. PM10 samples were collected over a 36-h period and Hg vapor was collected for eight-hour periods. PM10 mass was determined gravimetically and Hg (bound to PM10 and vapor) was extracted and analyzed by atomic absorption. Indoor levels of PM10 in the DSL ranged from 9.2 to 41.6 μg/m3 and 35.0 to 68.2 μg/m3 in the DC. Levels of particle-bound Hg ranged from 0.1 to 1.2 μg/m3 and in vapor 1.1 to 3.3mg/m 3 at the DSL; the DC levels ranged from <0.01 to 0.2 μg/m 3 for particle bound Hg and 13.6 to 102.7 μg/m3 in vapor. PM10 concentrations were below Indoor Air Quality suggested limits for total dust (100 μg/m3). Levels of mercury bound to PM 10 were low; however, mercury vapor was several times higher than the suggested OSHA (permissible exposure limit — 100 μg/m3) in the DSL.
Reorienting companies' hiring behaviour: an innovative `back-to-work' method in France
Authors: Salognon Marie
Published: November 2007

Current `back-to-work' programmes, particularly in France, tend to be built on a concept of personal responsibility for (long-term) unemployment and follow an `adaptive' approach: improving the `employability' of the unemployed, which is seen as an individual capacity, independent of the work and evaluation context. Our contribution justifies an alternative approach to back-to-work initiatives, so that society's share of responsibilities for long-term unemployment and social exclusion is taken into account within a collective, emergent and context-related conception of employability. Our study is based on observation of an innovative back-to-work programme in France (IOD) which seeks to change employers' assessment and recruitment practices to help vulnerable candidates who are generally discriminated against when seeking work.This interventionist approach aims to alter the demand side of the labour market and bring about changes in companies' practices to encourage more stable jobs and reduce selectivity in hiring.
Take off and Crash: Lessons from the Diverging Fates of the Brazilian and Argentine Aircraft Industries
Authors: Hira Anil , de Oliveira Luiz Guilherme
Published: November 2007

What are the factors that allow for success or failure of developing countries' attempts to enter high-tech sectors? We make a initial attempt to answer that question through a comparative study of success and failure in manufacturing aircraft. Aircraft production is one of the key industries in the world today, as reflected in the intense Boeing-Airbus rivalry. It is also one of the most cyclical, technologically-sophisticated, and capital-intensive industries, and therefore an unlikely place for a developing country to compete. But almost from the birth of modern commercial aircraft manufacturing, Argentina's Fábrica Militar de Aviones (FMA) was at the forefront of production. Brazil's aircraft industry was tiny in comparison at that time. Yet, by the 1990s, Brazil's Embraer had become the world's third largest aircraft manufacturer, while the Argentine aircraft industry has virtually disappeared. We examine the history of each company to explain the differences in trajectories and their fates. Our analysis demonstrates that an evolutionary but consistent partnership between state and firm, one attuned to both the exigencies of sectoral development and to changes in the nature of global markets, is necessary for success.
Membrane binding of the neuronal calcium sensor recoverin – modulatory role of the charged carboxy-terminus
Authors: Senin Ivan I , Churumova Valeriya A , Philippov Pavel P , Koch Karl-Wilhelm
Published: November 2007

Background

The Ca2+-binding protein recoverin operates as a Ca2+-sensor in vertebrate photoreceptor cells. It undergoes a so-called Ca2+-myristoyl switch when cytoplasmic Ca2+-concentrations fluctuate in the cell. Its covalently attached myristoyl-group is exposed at high Ca2+-concentrations and enables recoverin to associate with lipid bilayers and to inhibit its target rhodopsin kinase. At low Ca2+-concentrations the myristoyl group is inserted into a hydrophobic pocket of recoverin thereby relieving inhibitory constraint on rhodopsin kinase. Hydrophobic and electrostatic interactions of recoverin with membranes have not been clearly determined, in particular the function of the positively charged carboxy-terminus in recoverin 191QKVKEKLKEKKL202 in this context is poorly understood.

Results

Binding of myristoylated recoverin to lipid bilayer depends on the charge distribution in phospholipids. Binding was tested by equilibrium centrifugation and surface plasmon resonance (SPR) assays. It is enhanced to a certain degree by the inclusion of phosphatidylserine (up to 60%) in the lipid mixture. However, a recoverin mutant that lacked the charged carboxy-terminus displayed the same relative binding amplitudes as wildtype (WT) recoverin when bound to neutral or acidic lipids. Instead, the charged carboxy-terminus of recoverin has a significant impact on the biphasic dissociation of recoverin from membranes. On the other hand, the nonmyristoylated WT and truncated mutant form of recoverin did not bind to lipid bilayers to a substantial amount as binding amplitudes observed in SPR measurements are similar to bulk refractive index changes.

Conclusion

Our data indicate a small, but evident electrostatic contribution to the overall binding energy of recoverin association with lipid bilayer. Properties of the charged carboxy-terminus are consistent with a role of this region as an internal effector region that prolongs the time recoverin stays on the membrane by influencing its Ca2+-sensitivity.
Ubiquitin domain proteins in disease
Authors: Madsen Louise , Schulze Andrea , Seeger Michael , Hartmann-Petersen Rasmus
Published: November 2007

The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite their structural similarity, the UBL domains appear to have a range of different targets, resulting in a considerable diversity with respect to UDP function. Here, we give a short summary of the biochemical and physiological roles of the UDPs, which have been linked to human diseases including neurodegeneration and cancer.

Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
Roles and potential therapeutic targets of the ubiquitin proteasome system in muscle wasting
Authors: Nury David , Doucet Christine , Coux Olivier
Published: November 2007

Muscle wasting, characterized by the loss of protein mass in myofibers, is in most cases largely due to the activation of intracellular protein degradation by the ubiquitin proteasome system (UPS). During the last decade, mechanisms contributing to this activation have been unraveled and key mediators of this process identified. Even though much remains to be understood, the available information already suggests screens for new compounds inhibiting these mechanisms and highlights the potential for pharmaceutical drugs able to treat muscle wasting when it becomes deleterious. This review presents an overview of the main pathways contributing to UPS activation in muscle and describes the present state of efforts made to develop new strategies aimed at blocking or slowing muscle wasting.

Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
Mechanisms of Legionella pneumophila-induced interleukin-8 expression in human lung epithelial cells
Authors: Teruya Hiromitsu , Higa Futoshi , Akamine Morikazu , Ishikawa Chie , Okudaira Taeko , Tomimori Koh , Mukaida Naofumi , Tateyama Masao , Heuner Klaus , Fujita Jiro , Mori Naoki
Published: November 2007

Background

Legionella pneumophilais a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. We investigated the effect ofL. pneumophilaon the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines.

Results

Infection ofL. pneumophilastrain, but not heat-killed strain, resulted in upregulation of IL-8. IL-8 mRNA expression was induced immediately after the infection and its signal became gradually stronger until 24 h after infection. On the other hand, IL-8 expression in A549 cells infected withL. pneumophilalacking a functional type IV secretion system was transient. The IL-8 expression was slightly induced at 16 h and increased at 24 h after infection with flagellin-deficientLegionella. Activation of the IL-8 promoter byL. pneumophilainfection occurred through the action of nuclear factor-κB (NF-κB). Transfection of dominant negative mutants of NF-κB-inducing kinase, IκB kinase and IκB inhibitedL. pneumophila-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressedL. pneumophila-induced IL-8 mRNA due to deactivation of NF-κB.

Conclusion

Collectively, these results suggest thatL. pneumophilainduces activation of NF-κB through an intracellular signaling pathway that involves NF-κB-inducing kinase and IκB kinase, leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator inL. pneumophila-induced IL-8 expression, presumably contributing to immune response inL. pneumophila. The presence of flagellin and a type IV secretion system are critical forLegionellato induce IL-8 expression in lung epithelial cells.
A comparative analysis of predictive models of morbidity in intensive care unit after cardiac surgery – Part II: an illustrative example
Authors: Cevenini Gabriele , Barbini Emanuela , Scolletta Sabino , Biagioli Bonizella , Giomarelli Pierpaolo , Barbini Paolo
Published: November 2007

Background

Popular predictive models for estimating morbidity probability after heart surgery are compared critically in a unitary framework. The study is divided into two parts. In the first part modelling techniques and intrinsic strengths and weaknesses of different approaches were discussed from a theoretical point of view. In this second part the performances of the same models are evaluated in an illustrative example.

Methods

Eight models were developed: Bayes linear and quadratic models,k-nearest neighbour model, logistic regression model, Higgins and direct scoring systems and two feed-forward artificial neural networks with one and two layers. Cardiovascular, respiratory, neurological, renal, infectious and hemorrhagic complications were defined as morbidity. Training and testing sets each of 545 cases were used. The optimal set of predictors was chosen among a collection of 78 preoperative, intraoperative and postoperative variables by a stepwise procedure. Discrimination and calibration were evaluated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness-of-fit test, respectively.

Results

Scoring systems and the logistic regression model required the largest set of predictors, while Bayesian andk-nearest neighbour models were much more parsimonious. In testing data, all models showed acceptable discrimination capacities, however the Bayes quadratic model, using only three predictors, provided the best performance. All models showed satisfactory generalization ability: again the Bayes quadratic model exhibited the best generalization, while artificial neural networks and scoring systems gave the worst results. Finally, poor calibration was obtained when using scoring systems,k-nearest neighbour model and artificial neural networks, while Bayes (after recalibration) and logistic regression models gave adequate results.

Conclusion

Although all the predictive models showed acceptable discrimination performance in the example considered, the Bayes and logistic regression models seemed better than the others, because they also had good generalization and calibration. The Bayes quadratic model seemed to be a convincing alternative to the much more usual Bayes linear and logistic regression models. It showed its capacity to identify a minimum core of predictors generally recognized as essential to pragmatically evaluate the risk of developing morbidity after heart surgery.
Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells
Authors: Seo Dong-Cheol , Sung Ji-Min , Cho Hee-Jung , Yi Hee , Seo Kun-Ho , Choi In-Soo , Kim Dong-Ku , Kim Jin-Suk , El-Aty AM Abd , Shin Ho-Chul
Published: November 2007

Background

The studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells.

Results

We isolated CSCs from A549 cell line of which side population (SP) phenotype revealed several stem cell properties. After staining the cell line with Hoechst 33342 dye, the SP and non-side population (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression profiles were measured using an Affymetrix GeneChip® oligonucleotide array. Among the sixty one differentially expressed genes, the twelve genes inclusive three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2 (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up-regulated in SP compared to non-SP cells.

Conclusion

This is the first report indicating the differences of gene expression pattern between SP and non-SP cells in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1 and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor prognosis in anti-cancer therapy.
Regulation of the NFAT pathway discriminates CD4+CD25+ regulatory T cells from CD4+CD25− helper T cells
Authors: Sumpter Tina L , Payne Kyle K , Wilkes David S
Published: November 2007

CD4+CD25+ regulatory T cells (Tregs) are potent modulators of immune responses. The transcriptional program distinguishing Tregs from the CD4+CD25− Th cells is unclear. NFAT, a key transcription factor, is reported to interact with forkhead box p3, allowing inhibitory and activating signals in T cells. In the current study, we hypothesize that distinctive NFAT regulation in Tregs as compared with Th cells, may contribute to specific functions of these cells. Tregs express basal levels of cytoplasmic NFATc1 and NFATc2. In contrast to Th cells, anti-CD3-mediated T cell activation did not induce nuclear translocation of NFATc1 or NFATc2 in Tregs. This effect was associated with altered regulation for NFAT in Tregs that included reduced calcium flux, diminished calcineurin activation, and increased activity of glycogen synthase kinase-3β, a negative regulatory kinase for NFAT in Tregs relative to Th cells. These data suggested that NFAT inhibition in Th cells may induce regulatory function. Indeed, pharmacologically mediated NFAT inhibition induced Th cells to function as Tregs, an effect that was mediated by induction of membrane-bound TGF-β on Th cells. Collectively, these data suggest that maintaining NFAT at basal levels is a part of the transcriptional program required for Tregs.
Algorithmic Issues in Reverse Engineering of Protein and Gene Networks via the Modular Response Analysis Method
Authors: BERMAN PIOTR , DASGUPTA BHASKAR , SONTAG EDUARDO
Published: November 2007

Abstract:  This paper studies a computational problem motivated by the modular response analysis method for reverse engineering of protein and gene networks. This set‐cover problem is hard to solve exactly for large networks, but efficient approximation algorithms are given and their complexity is analyzed.
A Framework for Elucidating Regulatory Networks Based on Prior Information and Expression Data
Authors: GEVAERT OLIVIER , VAN VOOREN STEVEN , DE MOOR BART
Published: November 2007

Abstract:  Elucidating regulatory networks is an intensively studied topic in bioinformatics. Integration of different sources of information could facilitate this task. We propose to incorporate these information sources in the structure prior of a Bayesian network. We are currently investigating two complementary sources of information: PubMed abstracts combined with publicly available taxonomies or ontologies, and known protein–DNA interactions. These priors, either separately or combined, have the potential of reducing the complexity of reverse‐engineering regulatory networks while creating more robust and reliable models. Moreover this approach can easily be extended with other data sources. In such a way Bayesian networks provide a powerful framework for data integration and regulatory network modeling.
Dynamic Pathway Modeling
Authors: MAIWALD THOMAS , KREUTZ CLEMENS , PFEIFER ANDREA C. , BOHL SEBASTIAN , KLINGMÜLLER URSULA , TIMMER JENS
Published: November 2007

Abstract:  A major challenge in systems biology is to evaluate the feasibility of a biological research project prior to its realization. Since experiments are animals‐, cost‐ and time‐consuming, approaches allowing researchers to discriminate alternative hypotheses with a minimal set of experiments are highly desirable. Given a null hypothesis and alternative model, as well as laboratory constraints like observable players, sample size, noise level, and stimulation options, we suggest a method to obtain a list of required experiments in order to significantly reject the null hypothesis model M0 if a specified alternative model MA is realized. For this purpose, we estimate the power to detect a violation of M0 by means of Monte Carlo simulations. Iteratively, the power is maximized over all feasible stimulations of the system using multi‐experiment fitting, leading to an optimal combination of experimental settings to discriminate the null hypothesis and alternative model. We prove the importance of simultaneous modeling of combined experiments with quantitative, highly sampled in vivo measurements from the Jak/STAT5 signaling pathway in fibroblasts, stimulated with erythropoietin (Epo). Afterwards we apply the presented iterative experimental design approach to the Jak/STAT3 pathway of primary hepatocytes stimulated with IL‐6. Our approach offers the possibility of deciding which scientific questions can be answered based on existing laboratory constraints. To be able to concentrate on feasible questions on account of inexpensive computational simulations yields not only enormous cost and time saving, but also helps to specify realizable, systematic research projects in advance.