bluuebunny/crossref_metadata_2025 huggingface dataset:
Unstimulated whole saliva flow rate in relation to sicca symptoms in Hungary
Authors: Márton K , Madléna M , Bánóczy J , Varga G , Fejérdy P , Sreebny LM , Nagy G
Published: September 2007

Objective:  To assess the prevalence of xerostomia and the related oral and extraoral dryness symptoms in Hungary, to evaluate the association of those symptoms with the unstimulated whole saliva (UWS) flow rate, and to find correlation between the level of UWS flow rate and the oral health status of the questioned patients.

Subjects And Methods:  A total of 600 patients between the age of 18 and 92 years, 265 male, 335 female, were selected in accordance with the current regional age and residence distribution scheme of the Hungarian Statistical Office. A questionnaire was designed to determine the subjective presence or absence of the sicca symptoms. UWS flow rate and the dental and periodontal status were determined.

Results:  The percentages of subjective symptoms in the questioned subjects were oral dryness, 34%; reduced salivation, 11%; mucous saliva, 15%; dysphagia, 13%; glossopyrosis, 7%; dysphonia, 31%; dysgeusia, 9%; nasal dryness, 32%; ocular dryness, 21%; itching, 40% and xeroderma, 60%. Vaginal dryness was 14%, vaginal itching was 16% in the interviewed women. The grade of xerostomia, dysphagia, tiredness, and additionally the gingival bleeding index showed a negative correlation with the UWS flow rate. After all decayed, missing and filled teeth (DMF‐T) mean values, gingival bleeding index and plaque index were significantly higher in hyposalivators, compared with those who had normal flow rates

Conclusion:  This cross sectional study, representative of the Hungarian population, clearly shows that one‐third of the adult population suffers from xerostomia. The clinical severity of the xerostomia demonstrated a strong relationship with the lower levels of UWS flow rate. Reduced levels of UWS flow rate in this study were also shown to be associated with dysphagia, fatigue, and increased DMF‐T numbers. The data show that oral dryness, its associated desiccation symptoms and its clinical manifestations are significant health problems in Hungary.
Salivary free radical‐scavenging activity is affected by physical and mental activities
Authors: Atsumi T , Tonosaki K , Fujisawa S
Published: September 2007

Objective and design:  Free radicals/reactive oxygen species (ROS) are related to inflammation, aging, and cancer. However, living systems have essential antioxidant mechanisms by which these harmful radicals can be scavenged, i.e., free radical‐scavenging activity (FRSA). We measured the circadian rhythm of such activities by detecting salivary FRSA in healthy adults, and also examined how salivary FRSA is affected by physical and mental activities, which included (1) ingestion of beverage, (2) exercise, (3) comfortable/uncomfortable stimulation, and (4) smoking.

Methods:  FRSA was determined by using the DPPH (1,1′‐diphenyl‐2‐picrylhydrazyl) method. Statistical analysis for experimentally obtained median values was carried out using the Wilcoxon signed rank test.

Results:  In circadian rhythm, FRSA was increased by food ingestion and relaxation. As to the individual activities, green tea and coffee ingestion increased FRSA, whereas swimming (P < 0.05) and dance lessons (P < 0.01) decreased it. Watching an amusing video program (P < 0.001) or stimulation by a pleasant aroma (P < 0.01) increased FRSA. In contrast, an unpleasant odor had no effect on FRSA. FRSA decreased immediately after smoking (P < 0.05), but increased thereafter (P < 0.01).

Conclusion:  Salivary FRSA was affected not only by physical activities, but also by mental activities. It may be a parameter for reflecting the health status of individuals.
Immunohistochemical study of GLUT‐1 in oral peripheral nerve sheath tumors
Authors: Salla JT , Johann ACBR , Lana AMA , Do Carmo MAV , Nunes FD , Mesquita RA
Published: September 2007

Aim:  To investigate the immunoexpression and diagnostic applicability of human erythrocyte‐type glucose transporter protein (GLUT‐1) in oral peripheral nerve sheath tumors.

Material and methods:  Specimens diagnosed as oral peripheral nerve sheath tumors archived in the Oral Pathology Service of Universidade Federal de Minas Gerais from 1966 to 2006 were evaluated. Thirty‐four lesions were included: 15 traumatic neuromas, 11 neurofibromas, four neurilemmomas, and four malignant peripheral nerve sheath tumors (MPNST). One case of neurofibroma was associated with neurofibromatosis type I. Immunohistochemistry for S‐100 and GLUT‐1 was performed. S‐100 was immunopositive in all lesions.

Results:  Benign lesions were immunopositive for GLUT‐1 except in two (18.2%) cases of neurofibromas. In the traumatic neuroma, the perineuriums were immunopositive for GLUT‐1. In the neurofibroma, the immunoreactivity was heterogeneous. Immunopositivity was observed at levels of 54.5% in the periphery of the lesion, 9.1% in the center, and 18.2% in both. The neurilemmoma demonstrated immunopositivity in the capsule. One case (25%) of MPNST presented GLUT‐1 positive stain in occasional cells distributed homogeneously in all the tumor area.

Conclusion:  GLUT‐1 is a useful marker for perineurial cells and should be included in the oral peripheral nerve sheath tumors immunophenotyping thus aiding in the correct diagnosis of these lesions.
Recurring déjà vu associated with 5-hydroxytryptophan
Authors: Kalra Seema , Chancellor Andrew , Zeman Adam
Published: September 2007

Background:

Déjà vu occurs both in normal experience and as a neuropsychiatric symptom. Its pathogenesis is partially understood. We describe an iatrogenic case with implications for the neuropharmacological basis of déjà vu.

Case presentation:

A 42-year-old woman received 5-hydroxytryptophan, in combination with carbidopa, as treatment for palatal tremor, on two occasions, separated by 1 week. On each occasion, she experienced intense, protracted déjà vu, lasting for several hours. We discuss her case in relation to the neuroanatomical and neuropharmacological basis of déjà vu.

Conclusion:

The serotonergic system is involved in the genesis of déjà vu.
Pharmacologic chaperoning as a strategy to treat Gaucher disease
Authors: Yu Zhanqian , Sawkar Anu R. , Kelly Jeffery W.
Published: September 2007

We briefly introduce the most common lysosomal storage disorder, Gaucher disease, concisely describe the Food and Drug Administration approved strategies to ameliorate Gaucher disease, and then outline the emerging pharmacologic chaperone strategy that offers the promise to remedy this malady.
Glutamine and interleukin‐1β interact at the level of Sp1 and nuclear factor‐κB to regulate argininosuccinate synthetase gene expression
Authors: Brasse‐Lagnel Carole , Lavoinne Alain , Loeber David , Fairand Alain , Bôle‐Feysot Christine , Deniel Nicolas , Husson Annie
Published: September 2007

We previously demonstrated that the expression of the argininosuccinate synthetase (ASS) gene, a key step in nitric oxide production, is stimulated either by interleukin‐1β[Brasse‐Lagnel et al. (2005) Biochimie 87, 403–9] or by glutamine in Caco‐2 cells [Brasse‐Lagnel et al. (2003) J. Biol. Chem. 278, 52504–10], through the activation of transcription factors nuclear factor‐κB and Sp1, respectively. In these cells, the fact that glutamine stimulated the expression of a gene induced by pro‐inflammatory factors appeared paradoxical as the amino acid is known to exert anti‐inflammatory properties in intestinal cells. We therefore investigated the effect of simultaneous addition of both glutamine and interleukin‐1β on ASS gene expression in Caco‐2 cells. In the presence of both compounds for 4 h, the increases in ASS activity, protein amount and mRNA level were almost totally inhibited, implying a reciprocal inhibition between the amino acid and the cytokine. The inhibition was exerted at the level of the transcription factors Sp1 and nuclear‐κB: (a) interleukin‐1β inhibited the glutamine‐stimulated DNA‐binding of Sp1, which might be related to a decrease of its glutamine‐induced O‐glycosylation, and (b) glutamine induced per se a decrease in the amount of nuclear p65 protein without affecting the stimulating effect of interleukin‐1β on nuclear factor‐κB, which might be related to the metabolism of glutamine into glutamate. The present results constitute the first demonstration of a reciprocal inhibition between the effects of an amino acid and a cytokine on gene expression, and provide a molecular basis for the protective role of glutamine against inflammation in the intestine.
Metabolic gene switching in the murine female heart parallels enhanced mitochondrial respiratory function in response to oxidative stress
Authors: Essop M. Faadiel , Chan W. Y. A. , Taegtmeyer Heinrich
Published: September 2007

The mechanisms underlying increased cardioprotection in younger female mice are unclear. We hypothesized that serine‐threonine protein kinase (protein kinase B; Akt) triggers a metabolic gene switch (decreased fatty acids, increased glucose) in female hearts to enhance mitochondrial bioenergetic capacity, conferring protection against oxidative stress. Here, we employed male and female control (db/+) and obese (db/db) mice. We found diminished transcript levels of peroxisome proliferator‐activated receptor‐alpha, muscle‐type carnitine palmitoyltransferase 1 and pyruvate dehydrogenase kinase 4 in female control hearts versus male hearts. Moreover, females displayed improved recovery of cardiac mitochondrial respiratory function and higher ATP levels versus males in response to acute oxygen deprivation. All these changes were reversed in female db/db hearts. However, we found no significant gender‐based differences in levels of Akt, suggesting that Akt‐independent signaling mechanisms are responsible for the resilient mitochondrial phenotype observed in female mouse hearts. As glucose is a more energetically efficient fuel substrate when oxygen is limiting, this gene program may be a crucial component that enhances tolerance to oxygen deprivation in female hearts.
The intracellular region of the Notch ligand Jagged‐1 gains partial structure upon binding to synthetic membranes
Authors: Popovic Matija , De Biasio Alfredo , Pintar Alessandro , Pongor Sándor
Published: September 2007

Notch ligands are membrane‐spanning proteins made of a large extracellular region, a transmembrane segment, and a ∼ 100–200 residue cytoplasmic tail. The intracellular region of Jagged‐1, one of the five ligands to Notch receptors in man, mediates protein–protein interactions through the C‐terminal PDZ binding motif, is involved in receptor/ligand endocytosis triggered by mono‐ubiquitination, and, as a consequence of regulated intramembrane proteolysis, can be released into the cytosol as a signaling fragment. The intracellular region of Jagged‐1 may then exist in at least two forms: as a membrane‐tethered protein located at the interface between the membrane and the cytoplasm, and as a soluble nucleocytoplasmic protein. Here, we report the characterization, in different environments, of a recombinant protein corresponding to the human Jagged‐1 intracellular region (J1_tmic). In solution, J1_tmic behaves as an intrinsically disordered protein, but displays a significant helical propensity. In the presence of SDS micelles and phospholipid vesicles, used to mimick the interface between the plasma membrane and the cytosol, J1_tmic undergoes a substantial conformational change. We show that the interaction of J1_tmic with SDS micelles drives partial helix formation, as measured by circular dichroism, and that the helical content depends on pH in a reversible manner. An increase in the helical content is observed also in the presence of vesicles made of negatively charged, but not zwitterionic, phospholipids. We propose that this partial folding may have implications in the interactions of J1_tmic with its binding partners, as well as in its post‐translational modifications.
Protein lipidation
Authors: Nadolski Marissa J. , Linder Maurine E.
Published: September 2007

Proteins are covalently modified with a variety of lipids, including fatty acids, isoprenoids, and cholesterol. Lipid modifications play important roles in the localization and function of proteins. The focus of this review is S‐palmitoylation, the reversible addition of palmitate and other long‐chain fatty acids to proteins at cysteine residues in a variety of sequence contexts. The functional consequences of palmitoylation are diverse. Palmitoylation facilitates the association of proteins with membranes, mediates protein trafficking, and more recently has been appreciated as a regulator of protein stability. Members of a family of integral membrane proteins that harbor a DHHC cysteine‐rich domain mediate most cellular palmitoylation events. Here we focus on DHHC proteins that modify Ras proteins in yeast and mammalian cells.
Molecular mechanisms of the phospho‐dependent prolyl cis/trans isomerase Pin1
Authors: Lippens G. , Landrieu I. , Smet C.
Published: September 2007

Since its discovery 10 years ago, Pin1, a prolyl cis/trans isomerase essential for cell cycle progression, has been implicated in a large number of molecular processes related to human diseases, including cancer and Alzheimer's disease. Pin1 is made up of a WW interaction domain and a C‐terminal catalytic subunit, and several high‐resolution structures are available that have helped define its function. The enzymatic activity of Pin1 towards short peptides containing the pSer/Thr‐Pro motif has been well documented, and we discuss the available evidence for the molecular mechanisms of its isomerase activity. We further focus on those studies that examine its cis/trans isomerase function using full‐length protein substrates. The interpretation of this research has been further complicated by the observation that many of its pSer/Thr‐Pro substrate motifs are located in natively unstructured regions of polypeptides, and are characterized by minor populations of the cis conformer. Finally, we review the data on the possibility of alternative modes of substrate binding and the complex role that Pin1 plays in the degradation of its substrates. After considering the available work, it seems that further analysis is required to determine whether binding or catalysis is the primary mechanism through which Pin1 affects cell cycle progression.
Substrate recognition by the protein disulfide isomerases
Authors: Hatahet Feras , Ruddock Lloyd W.
Published: September 2007

Protein folding in the endoplasmic reticulum is often associated with the formation of native disulfide bonds. Their primary function is to stabilize the folded structure of the protein, although disulfide bond formation can also play a regulatory role. Native disulfide bond formation is not trivial, so it is often the rate‐limiting step of protein folding both in vivo and in vitro. Complex coordinated systems of molecular chaperones and protein folding catalysts have evolved to help proteins attain their correct folded conformation. This includes a family of enzymes involved in catalyzing thiol–disulfide exchange in the endoplasmic reticulum, the protein disulfide isomerase (PDI) family. There are now 17 reported PDI family members in the endoplasmic reticulum of human cells, but the functional differentiation of these is far from complete. Despite PDI being the first catalyst of protein folding reported, there is much that is still not known about its mechanisms of action. This review will focus on the interactions of the human PDI family members with substrates, including recent research on identifying and characterizing their substrate‐binding sites and on determining their natural substrates in vivo.
Role of different moieties from the lipooligosaccharide molecule in biological activities of the Moraxella catarrhalis outer membrane
Authors: Peng Daxin , Hu Wei‐Gang , Choudhury Biswa P. , Muszyński Artur , Carlson Russell W. , Gu Xin‐Xing
Published: September 2007

Lipooligosaccharide (LOS), a major component of the outer membrane of Moraxella catarrhalis, consists of two major moieties: a lipid A and a core oligosaccharide (OS). The core OS can be dissected into a linker and three OS chains. To gain an insight into the biological activities of the LOS molecules of M. catarrhalis, we used a random transposon mutagenesis approach with an LOS specific monoclonal antibody to construct a serotype A O35Elgt3 LOS mutant. MALDI‐TOF‐MS of de‐O‐acylated LOS from the mutant and glycosyl composition, linkage, and NMR analysis of its OS indicated that the LOS contained a truncated core OS and consisted of a Glc‐Kdo2 (linker)‐lipid A structure. Phenotypic analysis revealed that the mutant was similar to the wild‐type strain in its growth rate, toxicity and susceptibility to hydrophobic reagents. However, the mutant was sensitive to bactericidal activity of normal human serum and had a reduced adherence to human epithelial cells. These data, combined with our previous data obtained from mutants which contained only lipid A or lacked LOS, suggest that the complete OS chain moiety of the LOS is important for serum resistance and adherence to epithelial cells, whereas the linker moiety is critical for maintenance of the outer membrane integrity and stability to preserve normal cell growth. Both the lipid A and linker moieties contribute to the LOS toxicity.
A zinc finger HIT domain‐containing protein, ZNHIT‐1, interacts with orphan nuclear hormone receptor Rev‐erbβ and removes Rev‐erbβ‐induced inhibition of apoCIII transcription
Authors: Wang Jiadong , Li Yang , Zhang Min , Liu Zhongle , Wu Cong , Yuan Hanying , Li Yu‐Yang , Zhao Xin , Lu Hong
Published: September 2007

The orphan receptors, Rev‐erbα and Rev‐erbβ, are members of the nuclear receptor superfamily and specifically repress apolipoprotein CIII (apoCIII) gene expression in rats and humans. Moreover, Rev‐erbα null mutant mice have elevated very low density lipoprotein triacylglycerol and apoCIII levels. However, ligands for Rev‐erb are unknown and the regulatory mechanism of Rev‐erb is poorly understood. Conceivably, cofactors for Rev‐erb may play an important role in the regulation of lipid metabolism. In this study, a zinc finger HIT domain‐containing protein, ZNHIT‐1, interacted with Rev‐erbβ. ZNHIT‐1 was found to be a conserved protein in eukaryotes and was highly abundant in human liver. Furthermore, ZNHIT‐1 was identified as a nuclear protein. Serial truncated fragments and substitution mutations established a putative nuclear localization signal at amino acids 38–47 of ZNHIT‐1. A putative ligand‐binding domain of Rev‐erbβ and the FxxLL motif of ZNHIT‐1 were required for their interaction. Finally, ZNHIT‐1 was recruited by Rev‐erbβ to the apoCIII promoter and removed the Rev‐erbβ‐induced inhibition of apoCIII transcription. These findings demonstrate that ZNHIT‐1 functions as a cofactor to regulate the activity of Rev‐erbβ, and may play a role in lipid metabolism.
How might we achieve oxygen balance in wounds?
Authors: Davis Paul J
Published: September 2007

This paper describes the mechanism and physiological relevance of a new kind of oxygenating wound care technology, designed to deliver ‘oxygen balance’. It provides a continuous, controlled delivery of dissolved oxygen over an appropriate time scale, at the same time as providing all the required basics of wound care. Even though it is initially perceived as a simple dressing, it is an advanced, active biochemical process contained in a dressing structure, using the enzyme glucose oxidase to capture and transport oxygen from the atmosphere. With this technology, it is proposed that oxygen balance can be defined by relating the levels of achievable oxygenation to the cellular and biochemical activities required to bring about optimal wound healing.
Wound bed preparation and oxygen balance – a new component?
Authors: Sibbald R Gary , Woo Kevin Y , Queen Douglas
Published: September 2007

Chronic wounds have traditionally been treated by conservative means. It was Winter’s moist wound healing research, in 1962, that stimulated a proliferation of a moist interactive dressing technologies. Even considering this advancement in thinking, chronic wounds continue to be a problem for many clinicians. An increasing delineation of the science of healing in the past 20 years has redefined the way in which we both evaluate and treat wounds. This scientific understanding has raised wound care from the clinical problem arena to that of clinical specialty, where many now cross refer patients to specialists in this field. Wound bed preparation (WBP) has played a significant role in this change in practice. The concept has changed an ‘art’ of switching at random from one dressing to another, into a clinical science. WBP has come to the forefront as a major educational aid to help others develop appropriate treatment of the underlying disease causing the wound and patient requirements. The concept of WBP evolved over the recent years, becoming more and more sophisticated with time. Recent adaptations have brought together many of the current components. This article proposes yet another element of WBP, that of ‘oxygen balance’.
Effect of Braking Speed on Friction and Wear Behaviors of C/C‐SiC Composites
Authors: Zhang Junzhan , Xu Yongdong , Zhang Litong , Cheng Laifei
Published: September 2007

Carbon fiber‐reinforced silicon carbide matrix composites (C/C‐SiC) have received considerable attentions because of their superior friction and wear behaviors. In this paper, C/C‐SiC composites were fabricated by the reaction melt infiltration method, and the braking performance, the microstructure of friction surface, and wear debris at different braking speeds were also investigated. The mean coefficient of friction increases to the maximum value of 0.52 at 10 m/s and then declines afterwards with an increase in the braking speed. The higher coefficient of friction at low braking speed indicates the excellent braking performance of the C/C‐SiC composites for low braking energy. Excellent wear resistance is demonstrated by the low wear rate of the C/C‐SiC composites in comparison with C/C composites.
Effect of Firing Temperature on Electrical and Gas‐Sensing Properties of Nano‐SnO2‐Based Thick‐Film Resistors
Authors: Garje Anil D. , Aiyer Rohini C.
Published: September 2007

Nano‐SnO2‐based thick‐film resistors were fabricated using screen printing technology. To study the effect of firing temperature, sensors were fired in the range 425–850°C. A mixture of tetragonal and orthorhombic SnO2 was observed in the range 425–700°C. Above 700°C, the presence of majority tetragonal phase was observed. The sheet resistivity and TCR values were one to two orders of magnitude less than the reported values. Sensors fired at 750°C showed the highest sensitivity and selectivity for H2, CO, and LPG at 140°C, 210°C, and 180°C, respectively, with a response and recovery time of 12 and 22 s.
Development and Simulation of an Embedded Hydrogen Peroxide Catalyst Chamber in Low‐Temperature Co‐Fired Ceramics
Authors: Plumlee Donald , Steciak Judi , Moll Amy
Published: September 2007

Satellites in the range of 10–50 kg require small propulsion devices to perform station‐keeping tasks in orbit. Low‐temperature co‐fired ceramic structures provide a unique platform to produce a reliable, low‐cost micropropulsion system. The design uses microchannels embedded in the ceramic substrate to create a nozzle and embedded catalyst chamber. A hydrogen peroxide monopropellant is injected into a silver‐coated catalyst chamber structure. The monopropellant decomposes into hot gas, which is expelled through the nozzle producing thrust. A thermal energy balance and a kinetic model is presented along with performance testing.
Modelling and Characterizing a Screen‐Printed Metallic Electrothermal Microactuator
Authors: Ginet Patrick , Lucat Claude , Ménil Francis , Battaglia Jean‐Luc
Published: September 2007

A metallic electrothermal microactuator has been fabricated with screen‐printing technology based on a sacrificial layer process. The actuator, printed on a standard 96% alumina, consists of two linked copper beams of different widths partially suspended above the substrate to which they are anchored. Energy‐dispersive X‐rays analyses demonstrate the harmlessness of the process with regard to the metallic layer. While increasing DC voltage between both anchors of the electrothermal microactuator, the deflection is optically measured using a calibrated CCD camera. The temperature distribution measured with an infrared camera in the actuator compares well with that calculated with finite element simulations.
Mg–Cu–Zn Ferrites for Multilayer Inductors
Authors: Mürbe Julia , Töpfer Jörg
Published: September 2007

Mg–Cu–Zn ferrites can be sintered at T≤950°C to sufficient density and display adequate permeability profiles for application in multilayer ferrite inductors. The permeability and Curie temperature have to be optimized by proper selection of composition. Ferrites with <50 mol% Fe2O3 reveal enhanced densification behavior. Submicrometer powders prepared by fine milling show good sintering activity and density after firing at 900°C. Nano‐size ferrite powders prepared by coprecipitation or flame synthesis lead to high density; maximum shrinkage already occurs at T<800°C. The use of Bi2O3 as a sintering additive further improves the densification, but also affects the microstructure and, hence, the permeability. A maximum permeability of μi=450–500 is obtained.
Extreme recoils: impact on the detection of gravitational waves from massive black hole binaries
Authors: Sesana Alberto
Published: September 2007

Recent numerical simulations of the coalescence of highly spinning massive black hole binaries (MBHBs) suggest that the remnant can suffer a recoil velocity of the order of few thousand km s−1. We study here, by means of dedicated simulations of black hole build-up, how such extreme recoils could affect the cosmological coalescence rate of MBHBs, placing a robust lower limit for the predicted number of gravitational wave (GW) sources detectable by future space-borne missions (such as the Laser Interferometer Space Antenna, LISA). We consider two main routes for black hole formation: one where seeds are light remnants of Population III stars (≃102 M⊙), and one where seeds are much heavier (≳104 M⊙), formed via the direct gas collapse in primordial nuclear discs. We find that extreme recoil velocities do not compromise the efficient MBHB detection by LISA. If seeds are already massive and/or relatively rare, the detection rate is reduced by only ∼15 per cent. The number of detections drops substantially (by ∼60 per cent) if seeds are instead light and abundant, but in this case the number of predicted coalescences is so high that at least ∼10 sources in a three-year observation are guaranteed.
Low NaCl intake elevates renal medullary endothelin‐1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na+ excretion to ETA receptor blockade in rats
Authors: Klinger F. , Grimm R. , Steinbach A. , Tanneberger M. , Kunert‐Keil C. , Rettig R. , Grisk O.
Published: September 2007

Aims:  This study was performed to investigate the effects of NaCl intake on renal mRNA expression of pre‐pro‐endothelin‐1 (ET‐1), endothelin A (ETA) and endothelin B (ETB) receptors as well as on renal ET‐1 content in rats. We further tested for NaCl intake‐dependent differences in the contribution of the ET system to renal sodium handling.

Methods:  Male Sprague–Dawley rats with telemetric devices were randomized to 0.15%, 0.60% and 1.80% NaCl diets with or without losartan. Renal sodium balance and arterial pressure were monitored. Renal blood flow and fractional sodium excretion (FENa) were measured in response to acute infusion of ETA and ETB blockers into the inner stripe of the outer renal medulla.

Results:  Medullary pre‐pro‐ET‐1, ETA and ETB receptor mRNA was 50%, 81% and 33% higher in rats on 0.15% vs. 1.80% NaCl. Losartan reduced medullary gene expression in rats on 0.15% NaCl. Medullary ET‐1 content was 983 ± 88 and 479 ± 42 ng mg−1 protein in rats on 0.15% and 1.80% NaCl (P < 0.001). Chronic ETA receptor blocker treatment reduced arterial pressure by 8–10 mmHg in rats on 0.15% vs. 1.80% NaCl without affecting renal sodium balances. Acute medullary ETA or ETB receptor blockade did not alter medullary blood flow and FENa in animals on either diet.

Conclusion:  In rats renal medullary ET‐1 content and mRNA expression of three ET system components are inversely related to NaCl intake. Higher expression levels on low NaCl intake are AT1 receptor dependent but are not associated with increased sensitivity of renal sodium handling to ETA receptor blockade.
EndothelinA(ETA) and ETBreceptor‐mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla
Authors: Sullivan J. C. , Goodchild T. T. , Cai Z. , Pollock D. M. , Pollock J. S.
Published: September 2007

Aim: Our laboratory and others have shown that endothelin (ET)‐1 directly stimulates nitric oxide (NO) production in inner medullary collecting duct (IMCD) cells. The goal of this study was to determine which NO synthase (NOS) isoforms in IMCD are sensitive to ET‐1, and the role of ETAand ETBreceptor activationin vivoandin vitro.

Methods: NOS enzymatic activity and NOS isoform protein expression were examined in cultured IMCD‐3 cells and isolated renal inner medulla. ETBreceptor‐deficient homozygous rats (sl/sl) have elevated levels of circulating ET‐1 and lack a functional ETBsignalling pathway in kidneys, and furthermore provides a unique model to study ETAreceptor signalling in the renal inner medullain vivo.

Results: Incubation of IMCD‐3 cells with exogenous ET‐1 (50 nm) resulted in ETA‐dependent increased NOS1 protein expression in IMCD‐3 cells with no effect on NOS2 or NOS3 expression. ETBreceptor antagonism has no effect on NOS expression in IMCD‐3 cells. Consistent within vitroresults, cytosolic NOS1 protein expression was significantly greater in the renal inner medulla ofsl/slrats compared with heterozygous (sl/+)controls, with no alteration in NOS3 expression. In contrast to protein expression data, NOS1‐ and NOS3‐specific enzymatic activities decreased in the cytosolic fraction from the renal inner medulla ofsl/slcompared withsl/+.

Conclusion: These results provide evidence that both ETAand ETBreceptors regulate NOS isoform activity in the renal inner medulla and specifically support the hypothesis that ETAreceptor activation increases NOS1 expression.
Cytokine Response of Porcine Cell Lines to Salmonella enterica serovar Typhimurium and its hilA and ssrA mutants
Authors: Volf J. , Boyen F. , Faldyna M. , Pavlova B. , Navratilova J. , Rychlik I.
Published: September 2007

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterium which can infect and colonize pigs. After contact with enterocytes and macrophages, S. Typhimurium induces production of cytokines thus triggering the innate immune response. In this study we evaluated the cytokine response of two porcine cell lines, IPI‐2I and 3D4/31, of epithelial or macrophage origins, respectively, to the wild‐type S. Typhimurium and its hilA and ssrA mutants. We observed that the 3D4/31 cell line essentially did not respond to S. Typhimurium infection when a medium with foetal calf serum was used. However when the 3D4 cell line was incubated overnight in the presence of porcine serum, it efficiently responded to the wild‐type strain and the ssrA mutant but not to the noninvasive hilA mutant as measured by mRNA quantification of TNF‐α, IL‐8 and GM‐CSF by the real‐time RT‐PCR. In IPI‐2I, all the cytokines were also induced by the wild‐type S. Typhimurium and the ssrA mutant although the induction of TNF‐α was lower than that induced by the wild‐type strain. The hilA mutant was unable to induce any of the cytokines tested. The ssrA mutant can therefore be considered as more suitable for further vaccine development as the stimulation of innate immune response is important for animal protection against a challenge with virulent strains.
Evaluation of Indirect and Avidin–Biotin Enzyme Linked Immunosorbent Assays for Detection of Anti‐Listeriolysin O Antibodies in Bovine Milk Samples
Authors: Kalorey D. R. , Kurkure N. V. , Warke S. R. , Barbuddhe S. B.
Published: September 2007

Listeria monocytogenes is a foodborne pathogen that causes a wide spectrum of diseases in humans and animals. Enzyme linked immunosorbent assays (ELISA) [indirect and avidin–biotin (A–B)] for detecting L. monocytogenes antibodies in bovine milk samples (n = 2060) were standardized and evaluated by comparison with bacteriological examination. The tests were standardized by checker board titration. Highly purified listeriolysin O (LLO) was used as an antigen. Receiver operating characteristic (ROC) analysis was performed to decide the cut‐off values. The ROC analysis revealed the sensitivities of indirect and A–B ELISA as 100% and specificities as 97.1 and 99.9% respectively. Listeria monocytogenes was isolated from 105 (5.1%) milk samples collected from 52 farms. Anti‐LLO IgG antibodies were detected from 137 and 112 milk samples when tested by indirect and A–B ELISA respectively. Of the 52 farms screened, 28 (53.8%) yielded one or more isolates of L. monocytogenes and 33 (63.5%) of the farms had one or more animals simultaneously positive by one or both the assays for anti‐LLO antibodies.
Effect of Acidified Feed on the Prevalence of Salmonella in Market‐age Pigs
Authors: Creus E. , Pérez J. F. , Peralta B. , Baucells F. , Mateu E.
Published: September 2007

Two trials were carried out to determine the effect of feed acidification upon Salmonella carriage in market‐age pigs. In the first trial, the administration for the last 14 weeks of the fattening period of a commercial pelleted feed added with 0.6% lactic acid plus 0.6% formic acid (Lac‐Formic‐1.2) was compared to an unacidified standard diet (STD). A second experiment was carried out in two herds of growing pigs (Herd I, 3000 pigs; Herd II, 900 pigs) in which three different diets were assayed during the last 8–9 weeks of the fattening period: a diet containing 0.8% formic acid (Formic‐0.8), a diet containing 0.4% lactic acid plus 0.4% formic acid (Lac‐Formic‐0.8) and a STD. In the first experiment, serological evolution of the infection was examined by ELISA and microbiological cultures (rectal samples and mesenteric lymph nodes) were also done. Feed intake by pen and the individual weight of the animals were also measured. In the second trial, blood, rectal samples and mesenteric lymph nodes were collected at slaughter in both herds (30 pigs per experimental group). In the first experiment, the acidified diet (Lac‐Formic‐1.2) reduced Salmonella carriers in mesenteric lymph nodes (Fisher’s exact P < 0.01). In the second trial, Lac‐Formic‐0.8 diet significantly reduced Salmonella seroprevalence compared to the STD (P = 0.001) in both herds. Also Lac‐Formic‐0.8 and Formic‐0.8 diets in Herd II showed a lower faecal excretion and Salmonella carriage in mesenteric lymph nodes than the STD (P < 0.05). Our results suggest that the administration of a combination of lactic and formic acids at the levels used in this study could be used to reduce Salmonella prevalence in finishing pigs.
Optimization of Polymerase Chain Reaction for Detection of Clostridium botulinum Type C and D in Bovine Samples
Authors: Prévot V. , Tweepenninckx F. , Van Nerom E. , Linden A. , Content J. , Kimpe A.
Published: September 2007

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum. The economic, medical and alimentary consequences can be catastrophic in case of an epizooty. A polymerase chain reaction (PCR)‐based assay was developed for the detection of C. botulinum toxigenic strains type C and D in bovine samples. This assay has proved to be less expensive, faster and simpler to use than the mouse bioassay, the current reference method for diagnosis of C. botulinum toxigenic strains. Three pairs of primers were designed, one for global detection of C. botulinum types C and D (primer pair Y), and two strain‐specific pairs specifically designed for types C (primer pair VC) and D (primer pair VD). The PCR amplification conditions were optimized and evaluated on 13 bovine and two duck samples that had been previously tested by the mouse bioassay. In order to assess the impact of sample treatment, both DNA extracted from crude samples and three different enrichment broths (TYG, CMM, CMM followed by TYG) were tested. A 100% sensitivity was observed when samples were enriched for 5 days in CMM followed by 1 day in TYG broth. False‐negative results were encountered when C. botulinum was screened for in crude samples. These findings indicate that the current PCR is a reliable method for the detection of C. botulinum toxigenic strains type C and D in bovine samples but only after proper enrichment in CMM and TYG broth.
Lithography Technique for Topographical Micropatterning of Collagen-Glycosaminoglycan Membranes for Tissue Engineering Applications
Authors: Janakiraman Vijayakumar , Kienitz Brian L. , Baskaran Harihara
Published: September 2007

An adaptable technique for micropatterning biomaterial scaffolds has enormous implications in controlling cell function and in the development of tissue-engineered (TE) microvasculature. In this paper, we report a technique to embed microscale patterns onto a collagen-glycosaminoglycan (CG) membrane as a first step toward the creation of TE constructs with built-in microvasculature. The CG membranes were fabricated by homogenizing a solution of type-I bovine collagen and chondroitin-6-sulfate in acetic acid and vacuum filtering the solution subsequently. The micropatterning technique consisted of three steps: surface dissolution of base matrix using acetic acid solution, feature resolution by application of uniform pressure, and feature stability by glutaraldehyde cross-linking. Application of the new technique yielded patterns in CG membranes with a spatial resolution on the order of 2–3μm. We show that such a patterned matrix is conducive to the attachment of bovine aortic endothelial cells. The patterned membranes can be used for the development of complex three-dimensional TE products with built-in flow channels, as templates for topographically directed cell growth or as a model system to study various microvascular disorders where feature scales are important. The new technique is versatile; topographical patterns can be custom made for any predetermined design with high spatial resolution, and the technique itself can be adapted for use with other scaffold materials.
Device for Measurement of Human Tissue Properties In Vivo
Authors: Williams Robert L. , Ji Wei , Howell John N. , Conatser Robert R.
Published: September 2007

We present a method for measurement of human tissue compliance in vivo using a commercial haptic interface to apply known step changes in force while recording the resulting displacements. We introduce our system, the soft-tissue compliance meter. Our motivation was to improve the compliance realism of our virtual haptic back model, but there are many potential applications for this method. We present calibration of the haptic interface, pseudostatic compliance measurement techniques, measurement of contracted muscle compliances, and several important issues affecting our results.
Graphical Rendering of Localized Lumps for MIS Applications
Authors: Sokhanvar Saeed , Ramezanifard Mohammadreza , Dargahi Javad , Packirisamy Muthukumaran
Published: September 2007

Minimally invasive sugery (MIS) has increasingly been used in different surgical routines despite having significant shortcomings such as a lack of tactile feedback. Restoring this missing tactile information, particularly the information gained through tissue palpation, would be a significant enhancement to MIS capabilities. Tissue palpation is particularly important and commonly used in locating embedded lumps. The present study is inspired by this major limitation of the MIS procedure and is aimed at developing a system to reconstruct the lost palpation capability of surgeons in an effective way. By collecting necessary information on the size and location of hidden features using MIS graspers equipped with tactile sensors, the information can be processed and graphically rendered to the surgeon. Therefore, using the proposed system, surgeons can identify the presence or absence, location, and approximate size of hidden lumps simply by grasping the target organ with a smart endoscopic grasper. The results of the conducted experiments on the prototyped MIS graspers represented by graphical images are compared with those of the finite element models.
NetworKIN Depends on What You Do, Where You Are, and Who You Know
Authors: Adler Elizabeth M.
Published: September 2007

Signaling networks regulate cell behavior by means of posttranslational modifications that alter protein function. Phosphorylation, perhaps the most familiar of these modifications, constitutes a widespread regulatory mechanism: There are more than 500 human kinases, and thousands of phosphorylation sites have been identified. The limited specificity of phosphorylation consensus motifs, however, together with contextual factors that influence the likelihood that two proteins interact, have constrained our ability to determine precisely which protein phosphorylation sites constitute substrates for particular kinases. Linding
et al
. developed a computational approach, which they called NetworKIN, that combines predictions of kinase families likely to phosphorylate particular motifs with contextual information on substrates and kinases to predict which kinases mediate phosphorylation of specific sites. Accuracy in predicting the correct kinase family involved in phosphorylating a test group of known sites using contextual information was substantially improved compared with predictions based on consensus motifs alone. Indeed, in some cases, contextual information enabled prediction of the specific kinase involved. Application of the NetworKIN algorithm led to novel predictions that were confirmed experimentally. For instance, Rad50, part of a complex implicated in stabilizing broken chromosomes, was identified as a substrate of the kinase ATM (ataxia telangiectasia

mutated), which is activated in the DNA damage response, and 53BP1 was identified as a substrate for CDK1 (cyclin-dependent kinase 1). Combining the algorithm with quantitative mass spectrometry—a methodology potentially applicable to large-scale mapping of phosphorylation networks—suggested that the transcriptional repressor BCLAF1 (BCL2-associated transcription factor 1) is a substrate for GSK-3 (glycogen synthase kinase 3). Thus, including contextual information should facilitate modeling in vivo phosphorylation networks.

R. Linding, L. J. Jensen, G. J. Ostheimer, M. A. T. M. van Vugt, C. Jørgensen, I. M. Miron, F. Diella, K. Colwill, L. Taylor, K. Elder, P. Metalnikov, V. Nguyen, A. Pasculescu, J. Jin, J. G. Park, L. D. Samson, J. R. Woodgett, R. B. Russell, P. Bork, M. B. Yaffe, T. Pawson, Systematic discovery of in vivo phosphorylation networks.
Cell
129
, 1415-1426 (2007).
[PubMed]
Timeless Changes
Authors: Zahn Laura M.
Published: September 2007

Diapause, a developmental suspension in insects often occurring in the winter, is induced by temperature and light conditions, which for the fruit fly
Drosophila
vary significantly over its European range (see the Perspective by Bradshaw and Holzapfel). In
Drosophila
, the circadian rhythm gene
timeless
affects diapause, and Tauber
et al
. identify an allelic variant of
timeless
that can generate only one of the two known alternative forms of this protein. The coding variant, which affects the time when insects enter diapause, is found at higher frequencies at its putative origin and decreases in frequency in all directions along a latitudinal cline throughout Europe, which suggests the influence of environmental selection. Sandrelli
et al
. show that this variant results in more stable protein-protein interactions between timeless protein and its partners, which may explain the selective difference in the timing of diapause among individuals of different genotypes.

E. Tauber, M. Zordan, F. Sandrelli, M. Pegoraro, N. Osterwalder, C. Breda, A. Daga, A. Selmin, K. Monger, C. Benna, E. Rosato, C. P. Kyriacou, R. Costa, Natural selection favors a newly derived
timeless
allele in
Drosophila melanogaster
.
Science
316
, 1895-1898 (2007).
[Abstract]
[Full Text]

F. Sandrelli, E. Tauber, M. Pegoraro, G. Mazzotta, P. Cisotto, J. Landskron, R. Stanewsky, A. Piccin, E. Rosato, M. Zordan, R. Costa, C. P. Kyriacou, A molecular basis for natural selection at the
timeless
locus in
Drosophila melanogaster
.
Science
316
, 1898-1900 (2007).
[Abstract]
[Full Text]

W. Bradshaw, C. Holzapfel, Tantalizing
timeless
.
Science
316
, 1851-1852 (2007).
[Summary]
[Full Text]
Decap to Form Veins
Authors: Gough Nancy R.
Published: September 2007

The balance between synthesis and decay controls protein abundance at multiple levels. Goeres
et al
. found that a specific 5′→3′ mRNA degradation pathway involving an mRNA decapping complex was crucial for seedling development in
Arabidopsis thaliana
. The phenotypes of mutants in the
VCS
and
TDT
genes were similar, with defective leaf formation with vein defects, short roots with swollen root hairs, and short swollen hypocotyls. Confocal microscopy revealed that the shoot apical meristem cells were disorganized in the
vcs-7
and
tdt-1
plants and that leaf primordia were absent in seedlings that were 3 days old, which is when the leaf primordia appear in wild-type plants. Reporter gene analysis for vascular tissue and precursors suggested that the
tdt-1
mutant vascular phenotype arose as a consequence of defective formation of the provascular cell specification, which is controlled by auxin signaling, in the hypocotyl to cotyledon transition zone. Cloning revealed that TDT encoded a protein homologous to yeast and mammalian DCP2, a NUDIX and muT-domain containing mRNA decapping enzyme. VCS, which interacted with TDT in a yeast two-hybrid assay, appeared to be important for localizing TDT to cytoplasmic P-bodies, which are the sites of mRNA decapping and degradation. In
vcs-7
mutants, localization of a green fluorescent protein (GFP) TDT fusion protein to cytoplasmic foci with characteristics of P-bodies was lost. Analysis of specific mRNAs, as well as microarray analysis, indicated that TDT and VCS were involved in controlling mRNA abundance. However, not all mRNAs exhibited decreased decay rates, suggesting that this particular mRNA decay pathway was specific to a subset of transcripts. The transcripts that did accumulate in the mutants exhibited the presence of the 5′ cap, consistent with VCS and TDT as constituents of the decapping pathway.

D. C. Goeres, J. M. Van Norman, W. Zhang, N. A. Fauver, M. L. Spencer, L. E. Sieburth, Components of the
Arabidopsis
mRNA decappng complex are required for early seedling development.
Plant Cell
19
, 1549-1564 (2007).
[Abstract]
[Full Text]