Proximity of Na+–Ca2+-exchanger and sarco/endoplasmic reticulum Ca2+ pump in pig coronary artery smooth muscle: fluorescence microscopy

Pig coronary artery smooth muscle expresses the Na⁺–Ca²⁺-exchanger NCX1 and the sarco/endoplasmic reticulum (SER) Ca²⁺ pump SERCA2. NCX has been proposed to play a role in refilling the SER Ca²⁺ pool. Caveolae may also direct Ca²⁺ traffic during cell signaling. Here, we use immunofluorescence microscopy to determine if there is proximity between NCX1, SERCA2, and the caveolar protein caveolin-1. Stacks of images of cell surface domains were analyzed. Image stacks for one protein were analyzed for overlap with another protein, with and without randomization or image shifting. Within the resolution of light microscopy, there is significant overlap in the distributions of NCX1, SERCA2, and caveolin-1 but the three proteins are not always co-localized. The proximity between NCX1, SERCA2 is consistent with the assertion that NCX may supply Ca²⁺ for refilling the SER but this relationship is only partial. Similarly, caveolae may direct traffic in some Ca²⁺ signaling pathways but not others.     

Paecilotoxin production in clinical or terrestrial isolates of Paecilomyces lilacinus strains

The production of paecilotoxin from various isolates of Paecilomyces lilacinus was studied using three different media and high performance liquid chromatography (HPLC). Alkaline medium was found to be suitable for the production of the toxins. Among 20 strains tested, 19 including four clinical isolates were found to produce the toxins. Production patterns of paecilotoxins were very similar in each strain and the main toxins were A and B.     

Disassembly of preformed amyloid beta fibrils by small organofluorine molecules

A potential therapeutic approach for Alzheimer’s disease is to reduce the amount of toxic amyloid-beta oligomers and fibrillar amyloid plaques. In order to contribute to this approach the ability of small organofluorine compounds that were previously reported as successful inhibitors of fibrillogenesis to destabilize preformed fibrils of the amyloid-beta peptide was studied. These organofluorine molecules including chiral compounds were tested in vitro using standard methods based on Thioflavin-T (THT) fluorescence spectroscopy, atomic force microscopy (AFM) and Fourier-transform infrared spectroscopy (FTIR). It was observed that 5′-halogen substituted 3,3,3-trifluoromethyl-2-hydroxyl-(indol-3-yl)-propionic acid esters showed significant activity in the disassembly of the preformed fibrils. Since the same compounds were identified as strong fibrillogenesis inhibitors as well, this dual action makes them promising candidates for further drug development.     

Cell-cell signaling interactions coordinate multiple cell behaviors that drive morphogenesis of the lateral line

The zebrafish sensory lateral line system has emerged as a powerful model for the mechanistic study of collective cell migration and morphogenesis. Recent work has uncovered the details of a signaling network involving the Wnt/β-catenin, Fgf and Delta-Notch pathways that patterns the migrating lateral line primordium into distinct regions. Cells within these regions exhibit different fundamental behaviors that together orchestrate normal lateral line morphogenesis. In this review, we summarize the signaling network that patterns the migrating lateral line primordium and describe how this patterning coordinates crucial morphogenic cell behaviors.Key words: lateral line, Wnt signaling, Fgf signaling, collective migration, morphogenesis     

Exploration of a three-dimensional matrix as micro-reactor in the form of reactive polyaminosaccharide hydrogel beads using multipoint covalent interaction approach

Biotechnology Letters - Diversity in backbone polymer composition makes hydrogel-based resources open to broad spectrum of applications. Biomacromolecules which have reactive functional groups in...     

Antibacterial activity and cytotoxicity of a novel bacteriocin isolated from Pseudomonas sp. strain 166

Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q-Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS-PAGE and liquid chromatography–mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2–10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca²⁺, K⁺ and Mg²⁺. The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 μg ml⁻¹. Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.     

A Household Serosurvey to Estimate the Magnitude of a Dengue Outbreak in Mombasa,Kenya, 2013

Dengue appears to be endemic in Africa with a number of reported outbreaks. In February 2013, several individuals with dengue-like illnesses and negative malaria blood smears were identified in Mombasa, Kenya. Dengue was laboratory confirmed and an investigation was conducted to estimate the magnitude of local transmission including a serologic survey to determine incident dengue virus (DENV) infections. Consenting household members provided serum and were questioned regarding exposures and medical history. RT-PCR was used to identify current DENV infections and IgM anti-DENV ELISA to identify recent infections. Of 1,500 participants from 701 households, 210 (13%) had evidence of current or recent DENV infection. Among those infected, 93 (44%) reported fever in the past month. Most (68, 73%) febrile infected participants were seen by a clinician and all but one of 32 participants who reportedly received a diagnosis were clinically diagnosed as having malaria. Having open windows at night (OR = 2.3; CI: 1.1–4.8), not using daily mosquito repellent (OR = 1.6; CI: 1.0–2.8), and recent travel outside of Kenya (OR = 2.5; CI: 1.1–5.4) were associated with increased risk of DENV infection. This survey provided a robust measure of incident DENV infections in a setting where cases were often unrecognized and misdiagnosed.     

Hyperglycaemia,Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

Background

Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.

Methods

We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.

Findings

Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10⁻⁶mm²/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.

Conclusion

These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.

Trial Registration

ClinicalTrials.gov NCT00472381