The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.

Acid-sensing ion channels are members of the epithelial Na(+) channel/degenerin family. They are neuronal nonvoltage-gated Na(+) channels that are activated by extracellular acidification. In this study, we investigated the role of a highly conserved region of the extracellular part of ASIC1a that forms the contact between the finger domain, the adjacent beta-ball, and the upper palm domain in ASIC1a. The finger domain contributes to the pH-dependent gating and is linked via this contact zone to the rest of the protein. We found that mutation to Cys of residues in this region led to decreased channel expression and current amplitudes. Exposure of the engineered Cys residues to Cd(2+) or to charged methane thiosulfonate sulfhydryl reagents further reduced current amplitudes. This current inhibition was not due to changes in acid-sensing ion channel pH dependence or unitary conductance and was likely due to a decrease of the probability of channel opening. For some mutants, the effect of sulfhydryl reagents depended on the pH of exposure in the range 7.4 to 6.8, suggesting that this zone undergoes conformational changes during inactivation. Our study identifies a region in ASIC1a whose integrity is required for normal channel function.

Non-contact microdrilling of mouse zona pellucida with an objective-delivered 1.48-microns diode laser.

BACKGROUND and OBJECTIVE: A non-touch laser-induced microdrilling procedure is studied on mouse zona pellucida (ZP). STUDY DESIGN/MATERIALS and METHODS: A 1.48-microns diode laser beam is focused in a 8-microns spot through a 45x objective of an inverted microscope. Mouse zygotes, suspended in a culture medium, are microdrilled by exposing their ZP to a short laser irradiation and allowed to develop in vitro. RESULTS: Various sharp-edged holes can be generated in the ZP with a single laser irradiation. Sizes can be varied by changing irradiation time (3-100 ms) or laser power (22-55 mW). Drilled zygotes present no signs of thermal damage under light and scanning electron microscopy and develop as expected in vitro, except for a distinct eight-shaped hatching behavior. CONCLUSION: The microdrilling procedure can generate standardized holes in mouse ZP, without any visible side effects. The hole formation can be explained by a local photothermolysis of the protein matrix.

Radiographic total disc replacement angle measurement accuracy using the Oxford Cobbometer: precision and bias.

Total disc replacement (TDR) clinical success has been reported to be related to the residual motion of the operated level. Thus, accurate measurement of TDR range of motion (ROM) is of utmost importance. One commonly used tool in measuring ROM is the Oxford Cobbometer. Little is known however on its accuracy (precision and bias) in measuring TDR angles. The aim of this study was to assess the ability of the Cobbometer to accurately measure radiographic TDR angles. An anatomically accurate synthetic L4-L5 motion segment was instrumented with a CHARITE artificial disc. The TDR angle and anatomical position between L4 and L5 was fixed to prohibit motion while the motion segment was radiographically imaged in various degrees of rotation and elevation, representing a sample of possible patient placement positions. An experienced observer made ten readings of the TDR angle using the Cobbometer at each different position. The Cobbometer readings were analyzed to determine measurement accuracy at each position. Furthermore, analysis of variance was used to study rotation and elevation of the motion segment as treatment factors. Cobbometer TDR angle measurements were most accurate (highest precision and lowest bias) at the centered position (95.5%), which placed the TDR directly inline with the x-ray beam source without any rotation. In contrast, the lowest accuracy (75.2%) was observed in the most rotated and off-centered view. A difference as high as 4 degrees between readings at any individual position, and as high as 6 degrees between all the positions was observed. Furthermore, the Cobbometer was unable to detect the expected trend in TDR angle projection with changing position. Although the Cobbometer has been reported to be reliable in different clinical applications, it lacks the needed accuracy to measure TDR angles and ROM. More accurate ROM measurement methods need to be developed to help surgeons and researchers assess radiological success of TDRs.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

Habitat selection in zones of parapatric contact between the common shrew Sorex araneaus and Millet's shrew S. coronatus

(1) The common shrew Sorex araneus and Millet's shrew S. coronatusare sibling species.They are morphologically and genetically very similar but do not hybridize.Their parapatric distribution throughout south-western Europe, with a few narrow zones of distributional overlap, suggests that they are in competitive parapatry. (2) Two of these contact zones were studied; there was evidence of coexistence over periods of 2 years as well as habitat segregation. In both zones, the species segregated on litter thickness and humidity variables. (3) A simple analysis of spatial distribution showed that habitats visible in the field corresponded to the habitats selected by the species. Habitat selection was found throughout the annual life-cycle of the shrews. (4) In one contact zone, a removal experiment was performed to test whether habitat segregation is induced by interspecific interactions. The experiment showed that the species select habitats differentially when both are present and abandon habitat selection when their competitor removed. (5)These results confirm the role of resource partitioning in promoting narrow ranges of distributional overlap between such parapatric species and qualitatively support the prediction of habitat selection theory that, in a two-species system, coexistence may be achieved by differential habitat selection to avoid competition. The results also support the view that the common shrew and Millet's shrew are in competitive parapatry.

Microfibril angle and density patterns of fertilized and irrigated Norway spruce

Abstract

Methicillin-resistant Staphylococcus aureus with intermediate susceptibility to vancomycin: are strict additional contact measures sufficient?

Background: A hospitalised patient infected with MRSA was found to harbour a VISA strain after 6 weeks of treatment with vancomycin. Additional contact measures were reinforced according to CDCs recommendations. We decide to evaluate if these applied control measures were effective. Objective: To evaluate the efficacy of strict additional contact measures to contain the dissemination of VISA from an infected patient. Methods: All patients from the unit were screened weekly for MRSA during a 6-week period, whereas health care workers (HCW) were screened only once. Screening specimen included nose, throat, groin, and clinical specimens for patients, and only nose and throat for HCW. Broth enrichment and chromogenic agar (MRSA-select) were used for MRSA detection. All MRSA isolates were tested on Van screen plates, and growing colonies were tested for MIC of vancomycin. MIC was performed using Etest. Population analysis was done for VISA confirmation. One strain per person was typed by Double Locus Sequence Typing (based on clfB and spa sequencing). Results: 66 patients hospitalized in the same service during the 6 weeks and 55 HCW were screened for MRSA and VISA. MRSA was found in 16/66 (24%) patients and 1/55 (2%) HCW. 16/17 MRSA from patients belonged to the same genotype that the VISA strain. The remaining patient had a MRSA identical to the HCW isolate. Among the 16 MRSA isolates sharing the same genotype than the VISA strain, two showed Etests vancomycin MIC of only 4 mg/L. MIC results were confirmed by the population analysis. They were not considered as VISA, but as MRSA with increased vancomycin MICs. Both isolates were obtained from two roommates. Conclusion: Strict additional contact measures were found to be effective to contain VISA dissemination. However, the identification of two isolates with increased vancomycin MIC (4 mg/L) in two roommates raised the question of the need to routinely test this susceptibility and of adequate control measures for patients harbouring such isolates.

Characterization of the surface hydrophobicity of filamentous fungi.

A method for the quantitative analysis of the hydrophobicity of the mycelial mat of filamentous fungi based on contact angle measurements is presented. It was tested for a range of fungi belonging to the classes of basidiomycetes, ascomycetes and deuteromycetes. The measured contact angles of the mycelial mats ranged between hydrophilic (<30 degrees) for the deuteromycetes Fusarium oxysporum Fo47 GUS1 and Trichoderma harzianum P1[pZEGA1] and hydrophobic (>60 degrees) for the ascomycete Cladosporium sp. DSE48.1b and the basidiomycetes Paxillus involutus WSL 37.7, Hebeloma crustiliniforme WSL 6.2, Suillus bovinus WSL 48.1 and Laccaria bicolor WSL 73.1. For some fungi, variations in the hydrophobicity of the mycelium depending on the growth medium, the physiological state and the exposure to water were distinguished.

Theory of Wetting-Induced Fluid Entrainment by Advancing Contact Lines on Dry Surfaces

We report on the onset of fluid entrainment when a contact line is forced to advance over a dry solid of arbitrary wettability. We show that entrainment occurs at a critical advancing speed beyond which the balance between capillary, viscous, and contact-line forces sustaining the shape of the interface is no longer satisfied. Wetting couples to the hydrodynamics by setting both the morphology of the interface at small scales and the viscous friction of the front. We find that the critical deformation that the interface can sustain is controlled by the friction at the contact line and the viscosity contrast between the displacing and displaced fluids, leading to a rich variety of wetting-entrainment regimes. We discuss the potential use of our theory to measure contact-line forces using atomic force microscopy and to study entrainment under microfluidic conditions exploiting colloid-polymer fluids of ultralow surface tension.

Persistence of Increased Eotaxin-1 (CCL11) Level in Tears of Patients Wearing Contact Lenses: A Long-Term Follow-Up Study.

BACKGROUND: Eotaxin-1 (CCL11) is a potent eosinophil chemotactic and activating peptide that may be implicated in the pathogenesis of chronic allergic eye disease and has been associated with the wearing of contact lenses (CL) in patients with contact lens papillary conjunctivitis (CLPC). The purpose of this study was to study eotaxin-1 expression in the tears of long-term CL wearers. PATIENTS AND METHODS: Tears were collected with glass capillaries from 15 patients (2 male, 13 female) with various degree of CLPC at 2-year intervals. CLPC severity was graded from 0 to 4 with reference to standard slit-lamp photographs of the superior tarsal conjunctiva. The eotaxin-1 level in the tears was measured by an ELISA, using mouse anti-human eotaxin monoclonal antibodies. RESULTS: The mean age was 32.5 ± 13.3 years (range: 17 - 69 years). The mean interval between the tear collections was 30 ± 4.8 months. The mean concentration of eotaxin was 2150 ± 477 pg/mL and 2486 ± 810 pg/mL for the first and second series, respectively. The difference was not statistically significant (paired Wilcoxon/Kruskal-Wallis, p = 0.803). The mean score of papilla grade was 1.26 ± 0.18 for the first sample and 1.40 ± 0.19 two years later. There was no significant difference of grading between the two time periods (paired Wilcoxon/Kruskal-Wallis, p = 0.751). CONCLUSIONS: the eotaxin-1 level remains up-regulated over a long time period in patients wearing CL, most of them with chronic CLPC. Eotaxin may play a role in the pathogenesis of contact lens intolerance.

Gravity-driven slug motion in capillary tubes

The velocity of a liquid slug falling in a capillary tube is lower than predicted for Poiseuille flow due to presence of menisci, whose shapes are determined by the complex interplay of capillary, viscous, and gravitational forces. Due to the presence of menisci, a capillary pressure proportional to surface curvature acts on the slug and streamlines are bent close to the interface, resulting in enhanced viscous dissipation at the wedges. To determine the origin of drag-force increase relative to Poiseuille flow, we compute the force resultant acting on the slug by integrating Navier-Stokes equations over the liquid volume. Invoking relationships from differential geometry we demonstrate that the additional drag is due to viscous forces only and that no capillary drag of hydrodynamic origin exists (i.e., due to hydrodynamic deformation of the interface). Requiring that the force resultant is zero, we derive scaling laws for the steady velocity in the limit of small capillary numbers by estimating the leading order viscous dissipation in the different regions of the slug (i.e., the unperturbed Poiseuille-like bulk, the static menisci close to the tube axis and the dynamic regions close to the contact lines). Considering both partial and complete wetting, we find that the relationship between dimensionless velocity and weight is, in general, nonlinear. Whereas the relationship obtained for complete-wetting conditions is found in agreement with the experimental data of Bico and Quere [J. Bico and D. Quere, J. Colloid Interface Sci. 243, 262 (2001)], the scaling law under partial-wetting conditions is validated by numerical simulations performed with the Volume of Fluid method. The simulated steady velocities agree with the behavior predicted by the theoretical scaling laws in presence and in absence of static contact angle hysteresis. The numerical simulations suggest that wedge-flow dissipation alone cannot account for the entire additional drag and that the non-Poiseuille dissipation in the static menisci (not considered in previous studies) has to be considered for large contact angles.