Effect of Cavtratin, a Caveolin-1 Scaffolding Domain Peptide, on Oligodendroglial Signaling Cascades

Caveolin and caveolin containing rafts are involved in the signaling of growth factors in various cell types. Previous reports of our lab indicated a co-localization of caveolin and the high affinity nerve growth factor (NGF) receptor tyrosine kinase A (TrkA). Mutual effects have been observed among which a caveolin-1 knock-down resulted in an impairment of the NGF signaling cascade rather than in an increase of activity as expected from other growth factor reports. On the other hand, an over-expression of caveolin-1 impaired the NGF stimulated activity of p42/44 mitogen activated protein kinases (MAPK). In this study, we used a caveolin-1 scaffolding domain (CSD) peptide (cavtratin) of which an inhibitory effect on growth factor receptors was reported. Our data showed that cavtratin suppresses the NGF-induced phosphorylation of TrkA as well as the activation of MAPK in porcine oligodendrocytes significantly

Evaluation of the Charm maximum residue limit beta-lactam and tetracycline test for the detection of antibiotics in ewe and goat milk

The Charm maximum residue limit P-lactam and tetracycline test (Charm MRL BLTET; Charm Sciences Inc., Lawrence, MA) is an immunoreceptor assay utilizing Rapid. One-Step Assay lateral flow technology that detects P-lactam or tetracycline drugs in raw commingled cow milk at or below European Union maximum residue levels (EU-MRL). The Charm MRL BLTET test procedure was recently modified (dilution in buffer and longer incubation) by the manufacturers to be used with raw ewe and goat milk. To assess the Charm MRL BLTET test for the detection of beta-lactams and tetracyclines in milk of small ruminants, an evaluation study was performed at Instituto de Ciencia y Tecnologia Animal of Universitat Politecnica de Valencia (Spain). The test specificity and detection capability (CC beta) were studied following Commission Decision 2002/657/EC. Specificity results obtained in this study were optimal for individual milk free of antimicrobials from ewes (99.2% for beta-lactams and 100% for tetracyclines) and goats (97.9% for beta-lactams and 100% for tetracyclines) along the entire lactation period regardless of whether the results were visually or instrumentally interpreted. Moreover, no positive results were obtained when a relatively high concentration of different substances belonging to antimicrobial families other than beta-lactams and tetracyclines were present in ewe and goat milk. For both types of milk, the CC beta calculated was lower or equal to EU-MRL for amoxicillin (4 mu g/kg), ampicillin (4 mu g/kg), benzylpenicillin (30 mu g/kg). The CC beta for tetracyclines was also lower than EU-MRL for chlortetracycline (ewe milk: <= 50 mu g/kg; goat milk: 75 mu g/kg), oxytetracycline (<= 50 mu g/kg), and tetracycline (<= 50 mu g/kg). Regarding the 4-epimers of these tetracyclines only 4-epioxytetracycline was detected by the Charm MRL BLTET test below EU-MRL (ewe milk: 75 mu g/kg; goat milk: <= 50 mu g/kg). Acidiol had no effect on the performance of the test. The Charm MRL BLTET test could be used routinely with adapted test procedure for the fast screening of ewe and goat milk.This work forms part of the Project AGL2009-11524 financed by the Ministerio de Ciencia e Innovacion (Madrid, Spain). The authors are grateful to Fatro S.p.A. (Bologna, Italy) and ACS Dobfar S.p.A. (Milan, Italy) for kindly providing cefacetrile and desacetylcefapirin, respectively. Moreover, the authors thank Charm Sciences, Inc. (Lawrence, MA) and especially Wilbert Kokke from Charm Sciences Inc. and Raul Gomez from Grupo Taper, S.A. (Madrid, Spain) for their support.Beltrán Martínez, MC.; Romero Rueda, T.; Althaus, RL.; Molina Pons, MP. (2013). Evaluation of the Charm maximum residue limit beta-lactam and tetracycline test for the detection of antibiotics in ewe and goat milk. Journal of Dairy Science. 96(5):2737-2745. https://doi.org/10.3168/jds.2012-6044S2737274596

Different techniques of distal aortic repair in acute type A dissection: impact on late aortic morphology and reoperation

Objective: To compare three different techniques of distal aortic repair in acute type A (de Bakey type I) aortic dissection and to evaluate their impact on the late morphology of the aortic arch and descending aorta and on the incidence of reoperation. Methods: From 65 patients operated on due to an acute type A aortic dissection between 1989 and 1993, 54 long-term survivors underwent clinical and radiologic follow-up examination after a mean postoperative interval of 62±16 months. The surgical techniques of distal aortic reconstruction included closed repair using Teflon felt reinforcement under moderate hypothermic cardiopulmonary bypass (n=20) and open repair in deep hypothermic circulatory arrest using either Teflon felt reinforcement (n=16) or gelatin-resorcin-formaldehyde (GRF) glue (n=18) to readapt the dissected aortic layers. In all patients, MR imaging was performed on a 1.5-T whole body imaging system for the evaluation of the morphology and function of the heart, aorta and supraaortic branches. Results: Overall hospital mortality following surgical repair of type A aortic dissection was 15.4% during this time period. The highest rate of persistent false lumen perfusion (17/20, 85%) and presence of an intimal flap in the aortic arch (13/20, 65%) was observed in patients following closed repair of acute ascending aortic dissection, whereas the lowest rate of such findings was demonstrated in patients who had undergone open distal aortic repair using biological glue (false lumen perfusion 10/18, 55% and intimal flap in the arch 2/18, 11%). Redo-surgery was significantly reduced in the open repair group using GRF glue (1/18, 5.5%) as compared with the Teflon felt repair group (3/16, 18%) and the closed repair group (6/20, 30%). Conclusions: In patients with acute type A dissection, open distal aortic repair using GRF-glue favourably influences both (1) the severity of late morphologic alterations in the downstream aorta and (2) the incidence of reoperatio

How context can impact clinical trials : a multi-country qualitative case study comparison of diagnostic biomarker test interventions

Background Context matters for the successful implementation of medical interventions, but its role remains surprisingly understudied. Against the backdrop of antimicrobial resistance, a global health priority, we investigated the introduction of a rapid diagnostic biomarker test (C-reactive protein, or CRP) to guide antibiotic prescriptions in outpatient settings and asked, “Which factors account for cross-country variations in the effectiveness of CRP biomarker test interventions?” Methods We conducted a cross-case comparison of CRP point-of-care test trials across Yangon (Myanmar), Chiang Rai (Thailand), and Hanoi (Vietnam). Cross-sectional qualitative data were originally collected as part of each clinical trial to broaden their evidence base and help explain their respective results. We synthesised these data and developed a large qualitative data set comprising 130 interview and focus group participants (healthcare workers and patients) and nearly one million words worth of transcripts and interview notes. Inductive thematic analysis was used to identify contextual factors and compare them across the three case studies. As clinical trial outcomes, we considered patients’ and healthcare workers’ adherence to the biomarker test results, and patient exclusion to gauge the potential “impact” of CRP point-of-care testing on the population level. Results We identified three principal domains of contextual influences on intervention effectiveness. First, perceived risks from infectious diseases influenced the adherence of the clinical users (nurses, doctors). Second, the health system context related to all three intervention outcomes (via the health policy and antibiotic policy environment, and via health system structures and the ensuing utilisation patterns). Third, the demand-side context influenced the patient adherence to CRP point-of-care tests and exclusion from the intervention through variations in local healthcare-seeking behaviours, popular conceptions of illness and medicine, and the resulting utilisation of the health system. Conclusions Our study underscored the importance of contextual variation for the interpretation of clinical trial findings. Further research should investigate the range and magnitude of contextual effects on trial outcomes through meta-analyses of large sets of clinical trials. For this to be possible, clinical trials should collect qualitative and quantitative contextual information for instance on their disease, health system, and demand-side environment. Trial registration: ClinicalTrials.gov Identifiers NCT02758821 and NCT01918579

Labels direct infants’ attention to commonalities during novel category learning

Recent studies have provided evidence that labeling can influence the outcome of infants’ visual categorization. However, what exactly happens during learning remains unclear. Using eye-tracking, we examined infants’ attention to object parts during learning. Our analysis of looking behaviors during learning provide insights going beyond merely observing the learning outcome. Both labeling and non-labeling phrases facilitated category formation in 12-month-olds but not 8-month-olds (Experiment 1). Non-linguistic sounds did not produce this effect (Experiment 2). Detailed analyses of infants’ looking patterns during learning revealed that only infants who heard labels exhibited a rapid focus on the object part successive exemplars had in common. Although other linguistic stimuli may also be beneficial for learning, it is therefore concluded that labels have a unique impact on categorization

Principal component and Voronoi skeleton alternatives for curve reconstruction from noisy point sets

Surface reconstruction from noisy point samples must take into consideration the stochastic nature of the sample -- In other words, geometric algorithms reconstructing the surface or curve should not insist in following in a literal way each sampled point -- Instead, they must interpret the sample as a “point cloud” and try to build the surface as passing through the best possible (in the statistical sense) geometric locus that represents the sample -- This work presents two new methods to find a Piecewise Linear approximation from a Nyquist-compliant stochastic sampling of a quasi-planar C1 curve C(u) : R → R3, whose velocity vector never vanishes -- One of the methods articulates in an entirely new way Principal Component Analysis (statistical) and Voronoi-Delaunay (deterministic) approaches -- It uses these two methods to calculate the best possible tape-shaped polygon covering the planarised point set, and then approximates the manifold by the medial axis of such a polygon -- The other method applies Principal Component Analysis to find a direct Piecewise Linear approximation of C(u) -- A complexity comparison of these two methods is presented along with a qualitative comparison with previously developed ones -- It turns out that the method solely based on Principal Component Analysis is simpler and more robust for non self-intersecting curves -- For self-intersecting curves the Voronoi-Delaunay based Medial Axis approach is more robust, at the price of higher computational complexity -- An application is presented in Integration of meshes originated in range images of an art piece -- Such an application reaches the point of complete reconstruction of a unified mes

Algorithm engineering for optimal alignment of protein structure distance matrices

Protein structural alignment is an important problem in computational biology. In this paper, we present first successes on provably optimal pairwise alignment of protein inter-residue distance matrices, using the popular Dali scoring function. We introduce the structural alignment problem formally, which enables us to express a variety of scoring functions used in previous work as special cases in a unified framework. Further, we propose the first mathematical model for computing optimal structural alignments based on dense inter-residue distance matrices. We therefore reformulate the problem as a special graph problem and give a tight integer linear programming model. We then present algorithm engineering techniques to handle the huge integer linear programs of real-life distance matrix alignment problems. Applying these techniques, we can compute provably optimal Dali alignments for the very first time

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1–4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2–4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC

An asteroseismic test of diffusion theory in white dwarfs

The helium-atmosphere (DB) white dwarfs are commonly thought to be the descendants of the hotter PG1159 stars, which initially have uniform He/C/O atmospheres. In this evolutionary scenario, diffusion builds a pure He surface layer which gradually thickens as the star cools. In the temperature range of the pulsating DB white dwarfs (T_eff ~ 25,000 K) this transformation is still taking place, allowing asteroseismic tests of the theory. We have obtained dual-site observations of the pulsating DB star CBS114, to complement existing observations of the slightly cooler star GD358. We recover the 7 independent pulsation modes that were previously known, and we discover 4 new ones to provide additional constraints on the models. We perform objective global fitting of our updated double-layered envelope models to both sets of observations, leading to determinations of the envelope masses and pure He surface layers that qualitatively agree with the expectations of diffusion theory. These results provide new asteroseismic evidence supporting one of the central assumptions of spectral evolution theory, linking the DB white dwarfs to PG1159 stars.Comment: 7 pages, 3 figures, 3 tables, accepted for publication in A&