Formation of lipid bilayer membrane in a poly(dimethylsiloxane) microchip integrated with a stacked polycarbonate membrane support and an on-site nanoinjector

This paper describes a new and facile approach for the formation of pore-spanning bilayer lipid membranes (BLMs) within a poly(dimethylsiloxane) (PDMS) microfluidic device. Commercially, readily available polycarbonate (PC) membranes are employed for the support of BLMs. PC sheets with 5 mu m, 2 mu m, and 0.4 mu m pore diameters, respectively, are thermally bonded into a multilayer-stack, reducing the pore density of 0.4 mu m-pore PC by a factor of 200. The BLMs on this support are considerably stable (a mean lifetime: 17 h). This multilayer-stack PC (MSPC) membrane is integrated into the PDMS chip by an epoxy bonding method developed to secure durable bonding under the use of organic solvents. The microchip has a special channel for guiding a micropipette in the proximity of the MSPC support. With this on-site injection technique, tens to hundreds of nanoliters of solutions can be directly dispensed to the support. Incorporating gramicidin ion channels into BLMs on the MSPC support has confirmed the formation of single BLMs, which is based on the observation from current signals of 20 pS conductance that is typical to single channel opening. Based on the bilayer capacitance (1.4 pF), about 15% of through pores across the MSPC membrane are estimated to be covered with BLMs. (C) 2015 AIP Publishing LLC.open110sciescopu

Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

From Ultrasonography to High Resolution Magnetic Resonance Imaging: Towards an Optimal Management Strategy for Vulnerable Carotid Atherosclerotic Plaques

Stroke remains a major cause of death and disability worldwide, with approximately one-third of ischaemic strokes being a consequence of carotid atherosclerotic plaque rupture. Thus, diagnostic strategies that could identify those patients at highest risk of events are of critical importance.This work is supported by Heart Research UK (RG2638/14/16)

Optimization of fermentation medium for nisin production from Lactococcus lactis subsp. lactis using response surface methodology (RSM) combined with artificial neural network-genetic algorithm (ANN-GA)

Nisin is a bacteriocin approved in more than 50 countries as a safe natural food preservative. Response surface methodology (RSM) combined with artificial neural network-genetic algorithm (ANN-GA) was employed to optimize the fermentation medium for nisin production. Plackett-Burman design (PBD) was used for identifying the significant components in the fermentation medium. After that, the path of steepest ascent method (PSA) was employed to approach their optimal concentrations. Sequentially, Box-Behnken design experiments were implemented for further optimization. RSM combined with ANNGA were used for analysis of data. Specially, a RSM model was used for determining the individual effect and mutual interaction effect of tested variables on nisin titer (NT), an ANN model was used for NT prediction, and GA was employed to search for the optimum solutions based on the ANN model. As the optimal medium obtained by ANN-GA was located at the verge of the test region, a further Box- Behnken design based on the RSM statistical analysis results was implemented. ANN-GA was implemented using the further Box-Behnken design data to locate the optimum solution which was as follow (g/l): Glucose (GLU) 15.92, peptone (PEP) 30.57, yeast extraction powder (YEP) 39.07, NaCl 5.25, KH2PO4 10.00, and MgSO4·7H2O 0.20, with expected NT of 22216 IU/ml. The validation experiments with the optimum solution were implemented in triplicate and the average NT was 21423 IU/ml, which was 2.13 times higher than that without ANN-GA methods and 8.34 times higher than that without optimization.Key words: Response surface methodology, artificial neural network, genetic algorithm, nisin titer

Joint actions with large partners and small-firm ambidexterity in asymmetric alliances:The mediating role of relational identification

This study investigates the role of relational identification in the relation between joint actions and small-firm ambidexterity in asymmetric alliances. Using survey data on Chinese high-technology firms, we find that joint problem-solving and joint sensemaking are both positively associated with small firm's relational identification. We also find a positive relationship between small firm's relational identification and knowledge exploration and exploitation. More importantly, we show that relational identification mediates the relationships between joint actions (i.e., joint problem-solving and joint sensemaking) and small-firm ambidexterity, except for the relationship between joint sensemaking and small-firm knowledge exploitation. This study advances our understanding of the association between joint actions and ambidexterity by providing a social identification explanation

Sexual reproduction and genetic polymorphism within the cosmopolitan marine diatom Pseudo-nitzschia pungens.

Different clades belonging to the cosmopolitan marine diatom Pseudo-nitzschia pungens appear to be present in different oceanic environments, however, a 'hybrid zone', where populations of different clades interbreed, has also been reported. Many studies have investigated the sexual reproduction of P. pungens, focused on morphology and life cycle, rather than the role of sexual reproduction in mixing the genomes of their parents. We carried out crossing experiments to determine the sexual compatibility/incompatibility between different clades of P. pungens, and examined the genetic polymorphism in the ITS2 region. Sexual reproduction did not occur only between clades II and III under any of experimental temperature conditions. Four offspring strains were established between clade I and III successfully. Strains established from offspring were found interbreed with other offspring strains as well as viable with their parental strains. We confirmed the hybrid sequence patterns between clades I and III and found novel sequence types including polymorphic single nucleotide polymorphisms (SNPs) in the offspring strains. Our results implicate that gene exchange and mixing between different clades are still possible, and that sexual reproduction is a significant ecological strategy to maintain the genetic diversity within this diatom species

How Chromatin Is Remodelled during DNA Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

Global genome nucleotide excision repair removes DNA damage from transcriptionally silent regions of the genome. Relatively little is known about the molecular events that initiate and regulate this process in the context of chromatin. We've shown that, in response to UV radiation–induced DNA damage, increased histone H3 acetylation at lysine 9 and 14 correlates with changes in chromatin structure, and these alterations are associated with efficient global genome nucleotide excision repair in yeast. These changes depend on the presence of the Rad16 protein. Remarkably, constitutive hyperacetylation of histone H3 can suppress the requirement for Rad7 and Rad16, two components of a global genome repair complex, during repair. This reveals the connection between histone H3 acetylation and DNA repair. Here, we investigate how chromatin structure is modified following UV irradiation to facilitate DNA repair in yeast. Using a combination of chromatin immunoprecipitation to measure histone acetylation levels, histone acetylase occupancy in chromatin, MNase digestion, or restriction enzyme endonuclease accessibility assays to analyse chromatin structure, and finally nucleotide excision repair assays to examine DNA repair, we demonstrate that global genome nucleotide excision repair drives UV-induced chromatin remodelling by controlling histone H3 acetylation levels in chromatin. The concerted action of the ATPase and C3HC4 RING domains of Rad16 combine to regulate the occupancy of the histone acetyl transferase Gcn5 on chromatin in response to UV damage. We conclude that the global genome repair complex in yeast regulates UV-induced histone H3 acetylation by controlling the accessibility of the histone acetyl transferase Gcn5 in chromatin. The resultant changes in histone H3 acetylation promote chromatin remodelling necessary for efficient repair of DNA damage. Recent evidence suggests that GCN5 plays a role in NER in human cells. Our work provides important insight into how GG-NER operates in chromatin

Carbon nanotube/Co3O4 composite for air electrode of lithium-air battery

A carbon nanotube [CNT]/Co3O4 composite is introduced as a catalyst for the air electrode of lithium-air [Li/air] batteries. Co3O4 nanoparticles are successfully attached to the sidewall of the CNT by a hydrothermal method. A high discharge capacity and a low overvoltage indicate that the CNT/Co3O4 composite is a very promising catalyst for the air electrode of Li/air batteries

Rare gallbladder adenomyomatosis presenting as atypical cholecystitis: case report

<p>Abstract</p> <p>Background</p> <p>Gallbladder adenomyomatosis is a benign condition characterized by hyperplastic change in the gallbladder wall and overgrowth of the mucosa because of an unknown cause. Patients with gallbladder adenomyomatosis usually present with abdominal pain. However, we herein describe a case of a patient with gallbladder adenomyomatosis who did not present with abdominal pain, but with only fever.</p> <p>Case presentation</p> <p>A 34-year-old man presented to our hospital with a fever. No abdominal discomfort was declared. His physical examination showed no abnormalities. Ultrasound of the abdomen revealed thickness of the gallbladder. Acute cholecystitis was diagnosed. The fever persisted even after 1 week of antibiotic therapy. Magnetic resonance imaging of the abdomen showed gallbladder adenomyomatosis with intramural Rokitansky-Aschoff sinuses. Exploratory laparotomy with cholecystectomy was performed. The fever recovered and no residual symptoms were reported at the 3-year follow-up.</p> <p>Conclusions</p> <p>Gallbladder adenomyomatosis can present with fever as the only symptom. Although the association between gallbladder adenomyomatosis and malignancy has yet to be elucidated, previous reports have shown a strong association between gallbladder carcinoma and a subtype of gallbladder adenomyomatosis. Surgical intervention remains the first-choice treatment for patients with gallbladder adenomyomatosis.</p