bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability analysis for parametric generalized vector quasi-variational-like inequality problems
Authors: Agarwal Ravi P , Chen Jia-wei , Je Cho Yeol , Wan Zhongping
Published: March 2012

In this article, we consider a class of parametric generalized vector quasi-variational-like inequality problem (for short, (PGVQVLIP)) in Hausdorff topological vector spaces, where the constraint set K and a set-valued mapping T are perturbed by different parameters, and establish the nonemptiness and upper semicontinuity of the solution mapping S for (PGVQVLIP) under some suitable conditions. By virtue of the gap function, sufficient conditions for the H-continuity and B-continuity of the solution mapping S of (PGVQVLIP) are also derived. Moreover, examples are provided for illustrating the presented results.

2000 Mathematics Subject Classification: 49J40; 90C33.
An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases
Authors: Fiszer Agnieszka , Olejniczak Marta , Switonski Pawel M , Wroblewska Joanna P , Wisniewska-Kruk Joanna , Mykowska Agnieszka , Krzyzosiak Wlodzimierz J
Published: March 2012

Background

RNA interference (RNAi) and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ) disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting.

Results

Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge.

Conclusions

Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that combines the nonallele-selective gene silencing with the expression of the exogenous normal allele is a logical extension of the former and it deserves to be explored further. Both allele-selective RNAi approaches challenge cellular RNA interference machinery to show its ability to discriminate between similar sequences differing in either single base substitutions or repeated sequence length. Although both approaches perform well in allele discrimination most of our efforts are focused on repeat targeting due to its potentially higher universality.
Quantitative changes in intracellular calcium and extracellular-regulated kinase activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5-HT2A or 5-HT2Creceptors
Authors: Seitz Patricia K , Bremer Nicole M , McGinnis Andrew G , Cunningham Kathryn A , Watson Cheryl S
Published: March 2012

Background

The serotonin (5-HT) 2A and 2C receptors (5-HT2AR and 5-HT2CR) are involved in a wide range of physiological and behavioral processes in the mammalian central and peripheral nervous systems. These receptors share a high degree of homology, have overlapping pharmacological profiles, and utilize many of the same and richly diverse second messenger signaling systems. We have developed quantitative assays for cells stably expressing these two receptors involving minimal cell sample manipulations that dramatically improve parallel assessments of two signaling responses: intracellular calcium (Cai++) changes and activation (phosphorylation) of downstream kinases. Such profiles are needed to begin to understand the simultaneous contributions from the multiplicity of signaling cascades likely to be initiated by serotonergic ligands.

Results

We optimized theCai++assay for stable cell lines expressing either 5-HT2AR or 5-HT2CR (including dye use and measurement parameters; cell density and serum requirements). We adapted a quantitative 96-well plate immunoassay for pERK in the same cell lines. Similar cell density optima and time courses were observed for 5-HT2AR- and 5-HT2CR-expressing cells in generating both types of signaling. Both cell lines also require serum-free preincubation for maximal agonist responses in the pERK assay. However, 5-HT2AR-expressing cells showed significant release ofCai++in response to 5-HT stimulation even when preincubated in serum-replete medium, while the response was completely eliminated by serum in 5-HT2CR-expressing cells. Response to another serotonergic ligand (DOI) was eliminated by serum-replete preincubation in both cells lines.

Conclusions

These data expand our knowledge of differences in ligand-stimulated signaling cascades between 5-HT2AR and 5-HT2CR. Our parallel assays can be applied to other cell and receptor systems for monitoring and dissecting concurrent signaling responses.
The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro
Authors: Tabolacci Elisabetta , Pirozzi Filomena , Gomez-Mancilla Baltazar , Gasparini Fabrizio , Neri Giovanni
Published: March 2012

Background

Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to partially methylated FXS ones.

Methods

To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis.

Results

Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls.

Conclusions

These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1.
Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol in acute asthma: a double-blind, randomized controlled trial
Authors: Arun Jenish J , Lodha Rakesh , Kabra Sushil K
Published: March 2012

Background

There are no published studies that have compared bronchodilatory effect of inhaled budesonide/formoterol combination with budesonide/salbutamol delivered by metered dose inhaler with a spacer in acute exacerbation of asthma in children. We, therefore, compared the bronchodilatory effects of inhaled budesonide/formoterol (dose: 200 μg and 12 μg respectively) combination with budesonide (200 μg)/salbutamol (200 μg) administered by metered dose inhaler and spacer in children of 5-15 years with mild acute exacerbation of asthma [Modified Pulmonary Index Score (MPIS) between 6-8] in this double-blind, randomized controlled trial. The primary outcome was FEV1 (% predicted) in the two groups at 1, 5, 15, 30, 60 min after administration of the study drug.

Results

We did not observe any significant differences in the % predicted FEV1 and MPIS between formoterol and salbutamol at various time points from 1 min to 60 min post drug administration. There was significant improvement in FEV1 (% predicted) from baseline in both the groups as early as 1 min after drug administration.

Conclusions

Salbutamol or formoterol delivered along with inhaled corticosteroid by metered dose inhaler with spacer in children between 5-15 years of age with mild acute exacerbation of asthma had similar bronchodilatory effects.

Trial Registration

ClinicalTrials.gov: NCT00900874
The growth in newspaper coverage of tobacco control in China, 2000-2010
Authors: Gao Junling , Chapman Simon , Sun Shaojing , Fu Hua , Zheng Pinpin
Published: March 2012

Background

Media coverage of tobacco-related issues can potentially shape individual beliefs, attitudes and behaviors about tobacco use. This study aims to describe news coverage of tobacco control related issues in Chinese newspapers from 2000 to 2010.

Methods

All 1149 articles related to tobacco control were extracted from the Database of Chinese Important Newspapers and content analyzed for the period Jan 1, 2000 to Dec 31, 2010. The changing pattern of tobacco control topic, article type, viewpoint, and article origin, and their relationship were analysed.

Results

News coverage of tobacco control related issues increased significantly (p < 0.01) from 2000 to 2010, with news coverage being relatively intensive in May and June (p < 0.01), around World No Tobacco Day. 24.9% (n = 286) of all articles focused on secondhand smoke, 25.3% (n = 291) warned about the dangers of active smoking, and 10.0% (n = 115) focused on prevention and cessation programs and campaigns. Tobacco control topics varied significantly between national vs city/regional newspapers (χ
2 = 24.09, p = 0.002) and article types (χ
2 = 193.35, p < 0.001). Articles in national newspapers had more coverage of the dangers of tobacco and on enforcing bans on tobacco-advertising. News stories centered around monitoring tobacco use and smoke free activity, while editorials focused on enforcing bans on tobacco-advertising, youth access and programs and campaigns. Letters to editors focused on the dangers of smoking, raising tax, and smoking cessation. More articles (50.4%) took an anti-tobacco position (compared with 10.5% which were pro-smoking), with the amount of negative coverage growing significantly across the decade. National articles tended to lean toward anti-tobacco, however, local articles tended mix of pro-tobacco and neutral/balance positions. Editorials seemed to be more anti-tobacco oriented, but letters to the editor tended to show a mix of anti-tobacco and pro-tobacco positions.

Conclusion

Chinese newspapers are giving increasing attention to tobacco control, but coverage remains lower than in the USA and Australia. Health workers need to give higher priority to efforts to increase news coverage beyond the present concentration around World No Tobacco Day and to develop strategies for making tobacco control issues more newsworthy to both national and local news outlets.
Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm
Authors: Duraipandiyan Veeramuthu , Abdullah Al-Harbi Naif , Ignacimuthu Savarimuthu , Muthukumar Chinnasamy
Published: March 2012

Background

Costus speciosus (Koen ex.Retz.) Sm (Costaceae) is an Indian ornamental plant which has long been used medicinally in traditional systems of medicine. The plant has been found to possess diverse pharmacological activities. Rhizomes are used to treat pneumonia, rheumatism, dropsy, urinary diseases, jaundice, skin diseases and leaves are usedto treat mental disorders.

Method

Antibacterial and antifungal activities were tested using Disc diffusion method and Minimum Inhibitory Concentration (MIC). Column chromatography was used to isolate compounds from hexane extract. X-ray crystallography technique and GC-MS analysis were used to identify the compounds

Results

Antibacterial and antifungal activities were observed in hexane, chloroform, ethyl acetate and methanol extracts. Hexane extract of C.speciosus showed good activity against tested fungi also. Two sesquiterpenoid compounds were isolated (costunolide and eremanthin) from the hexane extract. Both the compounds did not inhibit the growth of tested bacteria. But, both the compounds inhibited the tested fungi. The compound costunolide showed significant antifungal activity. The MIC values of costunolide were; 62.5 μg/ml against Trichophyton mentagrophytes, 62. μg/ml against T. simii, 31.25 μg/ml against T. rubrum 296, 62.5 μg/ml against T. rubrum 57, 125 μg/ml against Epidermophyton floccosum, 250 μg/ml against Scopulariopsis sp, 250 μg/ml against Aspergillus niger, 125 μg/ml against Curvulari lunata, 250 μg/ml against Magnaporthe grisea.

Conclusion

Hexane extract showed promising antibacterial and antifungal activity. The isolated compound costunolide showed good antifungal activity.
Nanoscale measurement of the power spectral density of surface roughness: how to solve a difficult experimental challenge
Authors: González Martínez Juan Francisco , Nieto-Carvajal Inés , Abad José , Colchero Jaime
Published: March 2012

In this study, we show that the correct determination of surface morphology using scanning force microscopy (SFM) imaging and power spectral density (PSD) analysis of the surface roughness is an extremely demanding task that is easily affected by experimental parameters such as scan speed and feedback parameters. We present examples were the measured topography data is significantly influenced by the feedback response of the SFM system and the PSD curves calculated from this experimental data do not correspond to that of the true topography. Instead, either features are "lost" due to low pass filtering or features are "created" due to oscillation of the feedback loop. In order to overcome these serious problems we show that the interaction signal (error signal) can be used not only to quantitatively control but also to significantly improve the quality of the topography raw data used for the PSD analysis. In particular, the calibrated error signal image can be used in combination with the topography image in order to obtain a correct representation of surface morphology ("true" topographic image). From this "true" topographic image a faithful determination of the PSD of surface morphology is possible. The corresponding PSD curve is not affected by the fine-tuning of feedback parameters, and allows for much faster image acquisition speeds without loss of information in the PSD curve.
A review of communication-oriented optical wireless systems
Authors: Borah Deva K , Boucouvalas Anthony C , Davis Christopher C , Hranilovic Steve , Yiannopoulos Konstantinos
Published: March 2012

This article presents an overview of optical wireless (OW) communication systems that operate both in the short- (personal and indoor systems) and the long-range (outdoor and hybrid) regimes. Each of these areas is discussed in terms of (a) key requirements, (b) their application framework, (c) major impairments and applicable mitigation techniques, and (d) current and/or future trends. Personal communication systems are discussed within the context of point-to-point ultra-high speed data transfer. The most relevant application framework and related standards are presented, including the next generation Giga-IR standard that extends personal communication speeds to over 1 Gb/s. As far as indoor systems are concerned, emphasis is given on modeling the dispersive nature of indoor OW channels, on the limitations that dispersion imposes on user mobility and dispersion mitigation techniques. Visible light communication systems, which provide both illumination and communication over visible or hybrid visible/infrared LEDs, are presented as the most important representative of future indoor OW systems. The discussion on outdoor systems focuses on the impact of atmospheric effects on the optical channel and associated mitigation techniques that extend the realizable link lengths and transfer rates. Currently, outdoor OW is commercially available at 10 Gb/s Ethernet speeds for Metro networks and Local-Area-Network interconnections and speeds are expected to increase as faster and more reliable optical components become available. This article concludes with hybrid optical wireless/radio-frequency (OW/RF) systems that employ an additional RF link to improve the overall system reliability. Emphasis is given on cooperation techniques between the reliable RF subsystem and the broadband OW system.
Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury
Authors: Sobrado Mónica , Ramirez Belén G , Neria Fernando , Lizasoain Ignacio , Arbones Maria Lourdes , Minami Takashi , Redondo Juan Miguel , Moro María Ángeles , Cano Eva
Published: March 2012

Background

An increase in intracellular calcium concentration [Ca2+]iis one of the first events to take place after brain ischemia. A key [Ca2+]i-regulated signaling molecule is the phosphatase calcineurin (CN), which plays important roles in the modulation of inflammatory cascades. Here, we have analyzed the role of endogenous regulator of CN 1 (Rcan1) in response to experimental ischemic stroke induced by middle cerebral artery occlusion.

Methods

Animals were subjected to focal cerebral ischemia with reperfusion. To assess the role of Rcan1 after stroke, we measured infarct volume after 48 h of reperfusion inRcan1knockout (KO) and wild-type (WT) mice.In vitrostudies were performed in astrocyte-enriched cortical primary cultures subjected to 3% oxygen (hypoxia) and glucose deprivation (HGD). Adenoviral vectors were used to analyze the effect of overexpression of Rcan1-4 protein. Protein expression was examined by immunohistochemistry and immunoblotting and expression of mRNA by quantitative real-time Reverse-Transcription Polymerase Chain Reaction (real time qRT-PCR).

Results

Brain ischemia/reperfusion (I/R) injuryin vivoincreased mRNA and protein expression of the calcium-inducible Rcan1 isoform (Rcan1-4). I/R-inducible expression of Rcan1 protein occurred mainly in astroglial cells, and in anin vitromodel of ischemia, HGD treatment of primary murine astrocyte cultures induced Rcan1-4 mRNA and protein expression. Exogenous Rcan1-4 overexpression inhibited production of the inflammatory marker cyclo-oxygenase 2. Mice lacking Rcan1 had higher expression of inflammation associated genes, resulting in larger infarct volumes.

Conclusions

Our results support a protective role for Rcan1 during the inflammatory response to stroke, and underline the importance of the glial compartment in the inflammatory reaction that takes place after ischemia. Improved understanding of non-neuronal mechanisms in ischemic injury promises novel approaches to the treatment of acute ischemic stroke.
An acoustic communication based AQUA-GLOMO simulator for underwater networks
Authors: Dhurandher Sanjay K , Obaidat Mohammad S , Gupta Megha
Published: March 2012

In an underwater environment there can be various applications relating to the naval monitoring of an area and information gathering through the sensor nodes or underwater vehicles. The information gathered/monitored/detected in this manner can be sent to a group of sensors, or any sensor or vehicle may initiate a query asking for the information of its interest from the subset of the sensors. This information transfer or query dissemination can involve either broadcasting, multicasting or geocasting technique, depending on whether the query is sent to all the nodes, or a subset of nodes based on their locations. After developing any technique, it is required to validate it for its purpose. In underwater scenarios, testing any technique is not only costly but difficult too in terms of full deployment. Hence the next option is to test any modeled technique on a Simulator. A number of simulation tools have already been developed for the wired/wireless radio networks. However, these tools cannot be used for underwater environment with acoustic communication medium, as there is wide range of difference between the radio and the acoustic communications. Therefore, the acoustic communication based AQUA-GLOMO simulator has been implemented with GLOMOSIM as the base simulator. At the network layer, the RMTG model has also been included in this simulator that is an underwater sensor network geocasting model. The results obtained on this simulator have shown an evolving efficient simulator for underwater acoustic communications.
Intra-arrest hypothermia during cardiac arrest: a systematic review
Authors: Scolletta Sabino , Taccone Fabio Silvio , Nordberg Per , Donadello Katia , Vincent Jean-Louis , Castren Maaret
Published: March 2012

Introduction

Therapeutic hypothermia is largely used to protect the brain following return of spontaneous circulation (ROSC) after cardiac arrest (CA), but it is unclear whether we should start therapeutic hypothermia earlier, that is, before ROSC.

Methods

We performed a systematic search of PubMed, EMBASE, CINAHL, the Cochrane Library and Ovid/Medline databases using "arrest" OR "cardiac arrest" OR "heart arrest" AND "hypothermia" OR "therapeutic hypothermia" OR "cooling" as keywords. Only studies using intra-arrest therapeutic hypothermia (IATH) were selected for this review. Three authors independently assessed the validity of included studies and extracted data regarding characteristics of the studied cohort (animal or human) and the main outcomes related to the use of IATH: Mortality, neurological status and cardiac function (particularly, rate of ROSC).

Results

A total of 23 animal studies (level of evidence (LOE) 5) and five human studies, including one randomized controlled trial (LOE 1), one retrospective and one prospective controlled study (LOE 3), and two prospective studies without a control group (LOE 4), were identified. IATH improved survival and neurological outcomes when compared to normothermia and/or hypothermia after ROSC. IATH was also associated with improved ROSC rates and with improved cardiac function, including better left ventricular function, and reduced myocardial infarct size, when compared to normothermia.

Conclusions

IATH improves survival and neurological outcome when compared to normothermia and/or conventional hypothermia in experimental models of CA. Clinical data on the efficacy of IATH remain limited.
Streaming-potential coefficient of reservoir rock: A theoretical model
Authors: Glover Paul W. J. , Walker Emilie , Jackson Matthew D.
Published: March 2012

The streaming potential is that electrical potential which develops when an ionic fluid flows through the pores of a rock. It is an old concept that is recently being applied in many fields from monitoring water fronts in oil reservoirs to understanding the mechanisms behind synthetic earthquakes. We have carried out fundamental theoretical modeling of the streaming-potential coefficient as a function of pore fluid salinity, pH, and temperature by modifying the HS equation for use with porous rocks and using input parameters from established fundamental theory (the Debye screening length, the Stern-plane potential, the zeta potential, and the surface conductance). The model also requires the density, electrical conductivity, relative electric permittivity and dynamic viscosity of the bulk fluid, for which empirical models are used so that the temperature of the model may be varied. These parameters are then combined with parameters that describe the rock microstructure. The resulting theoretical values have been compared with a compilation of data for siliceous materials comprising 290 streaming-potential coefficient measurements and 269 zeta-potential measurements obtained experimentally for 17 matrix-fluid combinations (e.g., sandstone saturated with KCl), using data from 29 publications. The theoretical model was found to ably describe the main features of the data, whether taken together or on a sample by sample basis. The low-salinity regime was found to be controlled by surface conduction and rock microstructure, and was sensitive to changes in porosity, cementation exponent, formation factor, grain size, pore size and pore throat size as well as specific surface conductivity. The high-salinity regime was found to be subject to a zeta-potential offset that allows the streaming-potential coefficient to remain significant even as the saturation limit is approached.
Recurrent Hypoglycemia Is Associated with Loss of Activation in Rat Brain Cingulate Cortex
Authors: Hurst Paul , Garfield Alastair S. , Marrow Claire , Heisler Lora K. , Evans Mark L.
Published: March 2012

A subset of people with diabetes fail to mount defensive counterregulatory responses (CRR) to hypoglycemia. Although the mechanisms by which this occurs remain unclear, recurrent exposure to hypoglycemia may be an important etiological factor. We hypothesized that loss of CRR to recurrent exposure to hypoglycemia represents a type of stress desensitization, in which limbic brain circuitry involved in modulating stress responses might be implicated. Here, we compared activation of limbic brain regions associated with stress desensitization during acute hypoglycemia (AH) and recurrent hypoglycemia (RH). Healthy Sprague Dawley rats were exposed to either acute or recurrent 3-d hypoglycemia. We also examined whether changes in neuronal activation were caused directly by the CRR itself by infusing epinephrine, glucagon, and corticosterone without hypoglycemia. AH increased neuronal activity as quantified by c-fos immunoreactivity (FOS-IR) in the cingulate cortex and associated ectorhinal and perirhinal cortices but not in an adjacent control area (primary somatosensory cortex). FOS-IR was not observed after hormone infusion, suggesting that AH-associated activation was caused by hypoglycemia rather than by CRR. Importantly, AH FOS-IR activation was significantly blunted in rats exposed to RH. In conclusion, analogous with other models of stress habituation, activation in the cingulate cortex and associated brain areas is lost with exposure to RH. Our data support the hypothesis that limbic brain areas may be associated with the loss of CRR to RH in diabetes.
Dgp71WD is required for the assembly of the acentrosomal Meiosis I spindle, and is not a general targeting factor for the γ-TuRC
Authors: Reschen Richard F. , Colombie Nathalie , Wheatley Lucy , Dobbelaere Jeroen , St Johnston Daniel , Ohkura Hiro , Raff Jordan W.
Published: March 2012

Dgp71WD/Nedd1 proteins are essential for mitotic spindle formation. In human cells, Nedd1 targets γ-tubulin to both centrosomes and spindles, but in other organisms the function of Dgp71WD/Nedd1 is less clear. In Drosophila cells, Dgp71WD plays a major part in targeting γ-tubulin to spindles, but not centrosomes, while in Xenopus egg extracts, Nedd1 acts as a more general microtubule (MT) organiser that can function independently of γ-tubulin. The interpretation of these studies, however, is complicated by the fact that some residual Dgp71WD/Nedd1 is likely present in the cells/extracts analysed. Here we generate a Dgp71WD null mutant lacking all but the last 12 nucleotides of coding sequence. The complete loss of Dgp71WD has no quantifiable effect on γ-tubulin or Centrosomin recruitment to the centrosome in larval brain cells. The recruitment of γ-tubulin to spindle MTs, however, is severely impaired, and spindle MT density is reduced in a manner that is indistinguishable from cells lacking Augmin or γ-TuRC function. In contrast, the absence of Dgp71WD leads to defects in the assembly of the acentrosomal female Meiosis I spindle that are more severe than those seen in Augmin or γ-TuRC mutants, indicating that Dgp71WD has additional functions that are independent of these complexes in oocytes. Moreover, the localisation of bicoid RNA during oogenesis, which requires γ-TuRC function, is unperturbed in Dgp71WD120 mutants. Thus, Dgp71WD is not simply a general cofactor required for γ-TuRC and/or Augmin targeting, and it appears to have a crucial role independent of these complexes in the acentrosomal Meiosis I spindle.
CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl– conductance in the proximal colon of the possum,Trichosurus vulpecula
Authors: Fan Shujun , Harfoot Natalie , Bartolo Ray C. , Butt A. Grant
Published: March 2012

The cystic fibrosis transmembrane conductance regulator (CFTR) is central to anion secretion in both the possum and eutherian small intestine. Here, we investigated its role in the possum proximal colon, which has novel transport properties compared with the eutherian proximal colon. Despite considerable CFTR expression, high doses of the CFTR activator forskolin (EC50≈10 μmol l–1) were required for a modest, CFTR-dependent increase in short-circuit current (Isc) in the proximal colon. Presumably, this is because CFTR is restricted to the apical membrane of a small population of CFTR high expresser (CHE) cells in the surface and upper crypt epithelium. Furthermore, although the forskolin-stimulated Isc was dependent on serosal Na+, Cl– and HCO3–, consistent with anion secretion, inhibition of the basolateral Na–K–2Cl– (NKCC1) or Na–HCO3 (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed in CHE cells. At low doses (IC50≈1 μmol l–1), forskolin also decreased the transepithelial conductance (GT) of the colon through inhibition of a 4,4′-diisothiocyano-2,2′-stilbenedisulphonic acid-sensitive anion conductance in the basolateral membrane of the CHE cells. This conductance is arranged in series with CFTR in the CHE cells and, therefore, the CHE cells provide a transepithelial Cl– conductance for passive Cl– absorption across the epithelium. Inhibition of the basolateral Cl– conductance of the CHE cells by forskolin will inhibit Na+ absorption by restricting the movement of its counter-ion Cl–, assisting in the conversion of the tissue from an absorptive to a secretory state.
Corticosterone promotes emergence of fictive air breathing in Xenopus laevis Daudin tadpole brainstems
Authors: Fournier Stéphanie , Dubé Pierre-Luc , Kinkead Richard
Published: March 2012

The emergence of air breathing during amphibian metamorphosis requires significant changes to the brainstem circuits that generate and regulate breathing. However, the mechanisms controlling this developmental process are unknown. Because corticosterone plays an important role in the neuroendocrine regulation of amphibian metamorphosis, we tested the hypothesis that corticosterone augments fictive air breathing frequency in Xenopus laevis. To do so, we compared the fictive air breathing frequency produced by in vitro brainstem preparations from pre-metamorphic tadpoles and adult frogs before and after 1 h application of corticosterone (100 nmol l–1). Fictive breathing measurements related to gill and lung ventilation were recorded extracellularly from cranial nerve rootlets V and X. Corticosterone application had no immediate effect on respiratory-related motor output produced by brainstems from either developmental stage. One hour after corticosterone wash out, fictive lung ventilation frequency was increased whereas gill burst frequency was decreased. This effect was stage specific as it was significant only in preparations from tadpoles. GABA application (0.001–0.5 mmol l–1) augmented fictive air breathing in tadpole preparations. However, this effect of GABA was no longer observed following corticosterone treatment. An increase in circulating corticosterone is one of the endocrine processes that orchestrate central nervous system remodelling during metamorphosis. The age-specific effects of corticosterone application indicate that this hormone can act as an important regulator of respiratory control development in Xenopus tadpoles. Concurrent changes in GABAergic neurotransmission probably contribute to this maturation process, leading to the emergence of air breathing in this species.
Proteomic responses of blue mussel (Mytilus) congeners to temperature acclimation
Authors: Fields Peter A. , Zuzow Marcus J. , Tomanek Lars
Published: March 2012

The ability to acclimate to variable environmental conditions affects the biogeographic range of species, their success at colonizing new habitats, and their likelihood of surviving rapid anthropogenic climate change. Here we compared responses to temperature acclimation (4 weeks at 7, 13 and 19°C) in gill tissue of the warm-adapted intertidal blue mussel Mytilus galloprovincialis, an invasive species in the northeastern Pacific, and the cold-adapted M. trossulus, the native congener in the region, to better understand the physiological differences underlying the ongoing competition. Using two-dimensional gel electrophoresis and tandem mass spectrometry, we showed that warm acclimation caused changes in cytoskeletal composition and proteins of energy metabolism in both species, consistent with increasing rates of filtration and respiration due to increased ciliary activity. During cold acclimation, changes in cytoskeletal proteins were accompanied by increasing abundances of oxidative stress proteins and molecular chaperones, possibly because of the increased production of aldehydes as indicated by the upregulation of aldehyde dehydrogenase. The cold-adapted M. trossulus showed increased abundances of molecular chaperones at 19°C, but M. galloprovincialis did not, suggesting that the two species differ in their long-term upper thermal limits. In contrast, the warm-adapted M. galloprovincialis showed a stronger response to cold acclimation than M. trossulus, including changes in abundance in more proteins and differing protein expression profiles between 7 and 13°C, a pattern absent in M. trossulus. In general, increasing levels of oxidative stress proteins inversely correlate with modifications in Krebs cycle and electron transport chain proteins, indicating a trade-off between oxidative stress resistance and energy production. Overall, our results help explain why M. galloprovincialis has replaced M. trossulus in southern California over the last century, but also suggest that M. trossulus may maintain a competitive advantage at colder temperatures. Anthropogenic global warming may reinforce the advantage M. galloprovincialis has over M. trossulus in the warmer parts of the latter’s historical range.
Allocation of endogenous and dietary protein in the reconstitution of the gastrointestinal tract in migratory blackcaps at stopover sites
Authors: Muñoz-Garcia Agustí , Aamidor Sarah E. , McCue Marshall D. , McWilliams Scott R. , Pinshow Berry
Published: March 2012

During migratory flight, the mass of the gastrointestinal tract (GIT) and its associated organs in small birds decreases in size by as much as 40%, compared with the preflight condition because of the catabolism of protein. At stopover sites, birds need 2–3 days to rebuild their GIT so that they can restore body mass and fat reserves to continue migration. The source of protein used to rebuild the GIT may be exogenous (from food ingested) or endogenous (reallocated from other organs) or both. Because the relative contribution of these sources to rebuild the GIT of migratory birds is not yet known, we mimicked in-flight fasting and then re-feeding in two groups of blackcaps (Sylvia atricapilla), a Palearctic migratory passerine. The birds were fed a diet containing either 3% or 20% protein to simulate different refueling scenarios. During re-feeding, birds received known doses of 15N-l-leucine before we measured the isotope concentrations in GIT and associated digestive organs and in locomotory muscles. We then quantified the extent to which blackcaps rebuilt their GIT with endogenous and/or dietary protein while refeeding after a fast. Our results indicate that blackcaps fed the low-protein diet incorporated less exogenous nitrogen into their tissues than birds fed the 20% protein diet. They also allocated relatively more exogenous protein to the GIT than to pectoral muscle than those birds re-fed with the high-protein diet. However, this compensation was not sufficient for birds eating the low-protein diet to rebuild their intestine at the same rate as the birds re-fed the high-protein diet. We concluded that blackcaps must choose stopover sites at which they can maximize protein intake to minimize the time it takes to rebuild their GIT and, thus, resume migration as soon as possible.
Active uptake of artificial particles in the nematodeCaenorhabditis elegans
Authors: Kiyama Yuya , Miyahara Kohji , Ohshima Yasumi
Published: March 2012

Feeding and food choice are crucial to the survival of an animal. The nematode Caenorhabditis elegans feeds on various microorganisms in nature, and is usually fed Escherichia coli in the laboratory. To elucidate the mechanisms of food/non-food discrimination in C. elegans, we examined the accumulation of various fluorescent polystyrene microspheres in the absence and presence of bacterial food. In the absence of food and on agar plates, C. elegans worms actively accumulated 0.5 and 1 μm diameter microspheres, whereas those microspheres <0.5 μm or >3 μm were rarely accumulated. Carboxylate microspheres were accumulated more than sulfate or amine microspheres. These results of accumulation in the absence of food probably well simulate uptake of or feeding on the microspheres. Presence of food bacteria even at bacteria:nematode ratios of 1:100 or 1:10 significantly reduced accumulation of 0.5 μm microspheres, and accumulation was reduced to approximately one-fourth of that observed in the absence of bacteria at a ratio of 1:1. When accumulation of microspheres was examined with the chemical sense mutants che-2, tax-2, odr-1 and odr-2, or the feeding mutant eat-1, all the mutants showed less accumulation than the wild type in the absence of food. In the presence of food, the che-2 mutant showed more accumulation than the wild type. It is possible that C. elegans discriminates food both physically, based on size, and chemically, based on taste and olfaction.
Comparative characterization of Na+ transport in Cyprinodon variegatus variegatus and Cyprinodon variegatus hubbsi: a model species complex for studying teleost invasion of freshwater
Authors: Brix Kevin V. , Grosell Martin
Published: March 2012

The euryhaline fish Cyprinodon variegatus variegatus is capable of tolerating ambient salinities ranging from 0.3 to 160 PSU, but is incapable of long-term survival in freshwater (<2 mmol l–1 Na+). A population isolated in several freshwater (0.4–1 mmol l–1 Na+) lakes in central Florida is now designated as a subspecies (Cyprinodon variegatus hubbsi). We conducted a comparative study of Na+ transport kinetics in these two populations when acclimated to different ambient Na+ concentrations. Results reveal that the two subspecies have qualitatively similar low affinity Na+ uptake kinetics (Km=7000–38,000 μmol l–1) when acclimated to 2 or 7 mmol l–1 Na+, but C. v. hubbsi switches to a high affinity system (Km=100–140 μmol l–1) in low-Na+ freshwater (≤1 mmol l–1 Na+). Inhibitor experiments indicate that Na+ uptake in both subspecies is EIPA-sensitive, but sensitivity decreases with increasing external Na+. EIPA induced a 95% inhibition of Na+ influx in C. v. hubbsi acclimated to 0.1 mmol l–1 Na+, suggesting that this subspecies is utilizing a Na+/H+ exchanger to take up Na+ in low-Na+ environments despite theoretical thermodynamic constraints. Na+ uptake in C. v. hubbsi acclimated to 0.1 mmol l–1 Na+ is phenamil-sensitive but not bafilomycin-sensitive, leading to uncertainty about whether this subspecies also utilizes Na+ channels for Na+ uptake. Experiments with both subspecies acclimated to 7 mmol l–1 Na+ also indicate that a Cl–-dependent Na+ uptake pathway is present. This pathway is not metolazone-sensitive (NCC inhibitor) in either species but is bumetanide-sensitive in C. v. variegatus but not C. v. hubbsi. This suggests that an apical NKCC is increasingly involved with Na+ uptake for this subspecies as external Na+ increases. Finally, characterization of mitochondria-rich cell (MRC) size and density in fish acclimated to different ambient Na+ concentrations revealed significant increases in the number and size of emergent MRCs with decreasing ambient Na+. A linear relationship between the fractional area of emergent MRCs and Na+ uptake rate was observed for both subspecies. However, C. v. variegatus have lower Na+ uptake rates at a given MRC fractional area compared with C. v. hubbsi, indicating that the enhanced Na+ uptake by C. v. hubbsi at low ambient Na+ concentrations is not strictly a result of increased MRC fractional area, and other variables, such as differential expression of proteins involved in Na+ uptake, must provide C. v. hubbsi with the ability to osmoregulate in dilute freshwater.
The male blue crab,Callinectes sapidus, uses both chromatic and achromatic cues during mate choice
Authors: Baldwin Jamie , Johnsen Sönke
Published: March 2012

In the blue crab, Callinectes sapidus, claw color varies by sex, sexual maturity and individual. Males rely in part on color cues to select appropriate mates, and these chromatic cues may be perceived through an opponent interaction between two photoreceptors with maximum wavelength sensitivities at 440 and 508 nm. The range of color discrimination of this dichromatic visual system may be limited, however, and it is unclear whether male blue crabs are capable of discriminating the natural variations in claw color that may be important in mate choice. By testing males’ innate color preferences in binary choice tests between photographs of red-clawed females and six variations of orange-clawed females, we examined both the chromatic (opponent interaction) and achromatic (relative luminance) cues used in male mate choice. Males significantly preferred red-clawed females to orange-clawed females, except when the test colors were similar in both opponency and relative luminance. Our results are unusual in that they indicate that male mate choice in the blue crab is not guided solely by achromatic or chromatic mechanisms, suggesting that both color and intensity are used to evaluate female claw color.
General practice registrars as teachers: a questionnaire-based evaluation
Authors: Williams Bronwen , Amiel Cressida
Published: March 2012

Summary

Objectives

To determine how many General Practice (GP) Registrars in the London Deanery taught medical students during their final year of training. For those who did teach, to evaluate their experiences and for those who did not, to identify perceived barriers to teaching.

Design

Cross sectional survey of GP Registrars in the London Deanery completing their training in August 2010.

Setting

Online survey of GP Registrars sent after completion of training via the London Deanery GP Vocational Training Scheme (VTS) programme administrators.

Participants

GP Registrars in the London Deanery completing their training in August 2010.

Main outcome measure

The proportion of London Deanery GP registrars completing training in August 2010 who taught medical students during their registrar year.

Results

Over half of respondents were involved in some form of medical student teaching during their registrar year. Most of those who taught felt it enhanced their training, and the majority of those who did not teach would have liked to. Commonly cited barriers to teaching were: students not attached to the practice; not being given the opportunity to teach; and not having time to teach.

Conclusions

This evaluation demonstrated that GP registrars are either already involved with undergraduate teaching or want to get involved and the majority who teach feel that it enhances their training. A UK-wide study investigating the experiences and views of both GP registrars and GP trainers is warranted and qualitative work using focus groups or semistructured interviews would be valuable to develop the questionnaire for wider dissemination.
Pregabalin for the Treatment of Generalized Anxiety Disorder
Authors: Wensel Terri M , Powe Krystal W , Cates Marshall E
Published: March 2012

Objective:

To evaluate the efficacy and tolerability of pregabalin in the treatment of generalized anxiety disorder (GAD).

Data Sources:

A search of PubMed (1966-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was conducted using the MeSH and free-text terms pregabalin, anxiety disorders, and anxiety.

Study Selection and Data Extraction:

All English-language articles identified through the search were evaluated for inclusion. Only randomized controlled trials involving the use of pregabalin for the treatment of GAD were included in the review.

Data Synthesis:

Eight published trials were identified through the search strategy. Successful treatment of GAD with pregabalin versus placebo and active comparators has been reported in clinical trials. Pregabalin lowered total Hamilton Rating Scale for Anxiety scores within 1 week and was effective against both somatic and psychic subcomponents. In 1 controlled clinical trial, pregabalin was found to be effective in patients aged 65 years and older. Another trial demonstrated improved relapse rates when pregabalin, compared with placebo, was used for up to 6 months. The most commonly experienced adverse events were somnolence, dizziness, headache, and dry mouth.

Conclusions:

Available evidence suggests that pregabalin is effective and well tolerated in the treatment of GAD. As somnolence and dizziness are common adverse effects, caution should be used in elderly patients. Pregabalin rapidly relieves anxiety, a benefit that it may have over many other currently available therapeutic options besides benzodiazepines. While not a first-line therapy in GAD, pregabalin offers another treatment option in patients who do not respond to or who suffer intolerable adverse effects from other agents.
Proposing a Redefinition of Pharmaceutical Care
Authors: Blackburn David F , Yakiwchuk Erin M , Jorgenson Derek J , Mansell Kerry D
Published: March 2012

In many clinical practice settings, individual pharmaceutical care practitioners have thousands of patients who may receive their service. However, the pharmaceutical care approach provides virtually no guidance regarding how patients should be identified or prioritized by practicing pharmacists. We believe that pharmacists need to be “officially” accountable to specific patient groups at high risk for drug- or disease-induced morbidity within their practice. Consequently, the current definition of pharmaceutical care and its associated care processes need to be modified to ensure the activities of pharmacists are being focused on high-priority patients on a consistent basis.