AN OBJECTIVE NUMERICAL METHOD OF ASSESSING THE RELIABILITY OF TIME-INTENSITY PANELISTS

A measure of the reliability (T-IR) of time-intensity measurements was developed based on the concept of standard deviation as a measure of panelist variability. The T-IR measure was applied to time-intensity data collected from 10 panelists evaluating the sweetness of 4 model sweetener solutions on horizontal and vertical time-intensity line orientations. T-IR scores showed that the panelists were similarly reliable across the sweeteners and orientations. As well, independent of scale orientation, responses to sweeteners were similarly reliable. The T-IR measure can be used to maintain a high level of performance by monitoring time-intensity panelists. T-IR also provides an objective method of selecting panelists for time-intensity panels.     

Current-Voltage Curves of Single CI- Channels which Coexist with Two Types of K+ Channel in the Tonoplast of Chara corallina

A Cl^– channel and two types of K⁺ channel have been observed,by the use of the patch-clamp technique, in the membrane surroundingcytoplasmic droplets from Chara corallina. Measurements on cell-attachedpatches showed that the channel selective for Cl^– hada chord conductance of 21 pS at the resting membrane p.d. (mean= 11 mV, n = 19) and when open, passed an outward current of1.4 pA (n = 24 patches) at the resting p.d., with reversal ofthe direction of current at –54 mV (130 mol m^–3Cl^– in the external solution). The Cl^– concentrationin the cytoplasmic droplet calculated from the reversal p.d.was 15 mol m^–3. The channel strongly rectified outwardcurrent flow, but this rectification disappeared with symmetricalCl^– concentrations across detached patches of membrane.It is concluded that rectification observed in cell-attachedpatches is primarily due to asymmetric ^Cl– concentrationsrather than an asymmetry in energy barriers to Cl^– permeationin the channel or any voltage-dependent kinetics of the channel.The channel was rarely observed in detached patches despitebeing commonly observed in cell-attached patches. However, theabsence of Ca²⁺ at the cytoplasmic face of the membrane allowedobservation of the channel in detached patches for brief periods,during which ion substitution experiments revealed a permeabilitysequence of aspartate (76:33:1). A 100 pS K⁺ channel previously described by Luhring (1986) wasfrequently observed, in some instances simultaneously, witha channel having a conductance of 60 pS and displaying outwardrectification. This rectification was due to the channel remainingopen almost continuously for positive membrane potential differences(p.d.) and remaining shut almost continuously for negative p.d.'s.The 60 pS channel, like the 100 pS K⁺ channel, reversed currentflow at the resting p.d., suggesting that it was also permeableto K⁺. Key words: Plant ion-channels, chloride channel, potassium channel, patch-clamp     

Polymorphism and divergence at the prune locus in Drosophila melanogaster and D. simulans

The prune locus of Drosophila melanogaster lies at the tip of the X chromosome, in a region of reduced recombination in which nearby loci show reduced variation relative to evolutionary divergence from D. simulans. DNA sequencing of prune alleles from D. melanogaster and D. simulans reveals extremely low variation in D. melanogaster but greater variation in D. simulans. Divergence between the two species is not reduced. This pattern may be explained by either positive selection leading to hitchhiking of neutral variation or background selection against deleterious mutations. The pattern of silent versus replacement polymorphism and divergence at prune is consistent with either a model of weakly deleterious selection against amino acid substitutions or balancing selection.      

Ionic Currents across the Plasmalemma of Chara inflata Cells: I. OSMOTIC EFFECTS OF SORBITOL ON K+, CI- AND LEAK CURRENTS

This paper describes experiments designed to investigate theeffects of increases in external osmotic pressure on the electrophysiologicalbehaviour of the plasmalemma in cells of the brackish-wateralga, Chara inflata. The electrical conductance of the plasmalemmaof these cells of, due to the diffusion of ions, consists mainlyof K⁺, Cl^– and leak components. The addition of sorbitolat concentrations in the range 40–280 mol m^–3 tothe external solution bathing the cells, progressively and reversiblydepolarized the cell membrane and increased the total membraneconductance, chiefly due to increases in each of the separateionic conductances. At concentrations higher than about 280mol m^–3 when the cells became plasmolysed, the effectsof sorbitol on the electrical properties of the cell ceasedto be fully reversible. When the membrane electrical potentialdifference is stepped in a negative direction with a voltage-clamp,the resulting inward current has voltage-dependent componentsconsisting of an inactivating K⁺ current, an activating Cl^–current and a constant leak current. The addition of sorbitolto the external solution modified these currents by increasingtheir magnitude, by increasing the half-time of the inactivationof the K⁺ current, and by decreasing the half-time of activationof the Cl^– current. Key words: Chara inflata, osmotic effects, K⁺ and Cl^– currents     

Iron‐mediated suppression of bloom‐forming cyanobacteria by oxine in a eutrophic lake

1. Published studies show that cyanobacteria have higher Fe requirements than eukaryotic algae. To test whether Fe availability can affect formation of a cyanobacterial bloom, a strong Fe chelator, oxine (8‐hydroxyquinoline, C₉H₇NO), was added to enclosures in eutrophic Lake 227 in the Experimental Lakes Area (ELA) (northwestern Ontario). 2. Aphanizomenon schindlerii growth was suppressed, and growth of eukaryotic chlorophytes significantly promoted in enclosures to which oxine had been added. Significant eukaryotic growth did not occur in enclosures treated with ammonium, suggesting that N supplied by degradation of oxine was not responsible for eukaryotic success in the oxine enclosures. 3. In situ Fe²⁺ measurements were unreliable because of interference from high concentrations of dissolved organic compounds. However, oxine rapidly promoted oxidation of Fe²⁺ to Fe³⁺ in deionised water, suggesting that rapid removal of Fe²⁺ also occurred in the oxine‐treated enclosures. 4. In batch cultures, 10 μm Fe and 10 μm oxine (a 1 : 1 ratio) completely inhibited the growth of the cyanobacteria Synechococcus sp. and Anabaena flos‐aquae and the chlorophytes Pseudokirchneriella subcapitata and Scenedesmus quadricauda. Increasing Fe 10‐fold to 100 μm Fe completely and partially reversed oxine inhibition in the two chlorophytes but could not overcome inhibition of the cyanobacteria, indicating that inhibition was Fe‐mediated at least in the eukaryotes. Since oxine binds Fe³⁺ in a 1 : 3 ratio (Fe : oxine), inhibition at a 1 : 1 ratio indicates that not all of the Fe is bound, and a mechanism involving Fe other than chelation was at least partly responsible for inhibition. 5. Collectively, the enclosure and laboratory results suggest that the outcome of competition between cyanobacteria and eukaryotic algae in the oxine‐treated enclosures in Lake 227 was likely a result of decreased availability of Fe, especially Fe²⁺. 6. The results suggest that remediation methods that dramatically restrict the supply rate of Fe²⁺ could reduce the relative abundance of cyanobacteria in eutrophic systems.     

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Methods/Design

A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.

Discussion

The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.

Trial registration

Dutch Trial Register, NTR1447.

     

Type I IFN and TNFα cross-regulation in immune-mediated inflammatory disease: basic concepts and clinical relevance

A cross-regulation between type I IFN and TNFα has been proposed recently, where both cytokines are hypothesized to counteract each other. According to this model, different autoimmune diseases can be viewed as disequilibrium between both cytokines. As this model may have important clinical implications, the present review summarizes and discusses the currently available clinical evidence arguing for or against the proposed cross-regulation between TNFα and type I IFN. In addition, we review how this cross-regulation works at the cellular and molecular levels. Finally, we discuss the clinical relevance of this proposed cross-regulation for biological therapies such as type I IFN or anti-TNFα treatment.     

Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment

Introduction  

Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.