Platinum Cyclooctadiene Complexes with Activity against Gram-positive Bacteria

Antimicrobial resistance is a looming health crisis, and it is becoming increasingly clear that organic chemistry alone is not sufficient to continue to provide the world with novel and effective antibiotics. Recently there has been an increased number of reports describing promising antimicrobial properties of metal-containing compounds. Platinum complexes are well known in the field of inorganic medicinal chemistry for their tremendous success as anticancer agents. Here we report on the promising antibacterial properties of platinum cyclooctadiene (COD) complexes. Amongst the 15 compounds studied, the simplest compounds Pt(COD)X₂ (X=Cl, I, Pt1 and Pt2 ) showed excellent activity against a panel of Gram-positive bacteria including vancomycin and methicillin resistant Staphylococcus aureus. Additionally, the lead compounds show no toxicity against mammalian cells or haemolytic properties at the highest tested concentrations, indicating that the observed activity is specific against bacteria. Finally, these compounds showed no toxicity against Galleria mellonella at the highest measured concentrations. However, preliminary efficacy studies in the same animal model found no decrease in bacterial load upon treatment with Pt1 and Pt2 . Serum exchange studies suggest that these compounds exhibit high serum binding which reduces their bioavailability in vivo, mandating alternative administration routes such as e. g. topical application.     

The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation

Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. TSC affects multiple organs including the brain. The neurologic manifestation is characterized by cortical tubers, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA) in brain. SEGAs may result in hydrocephalus in TSC patients and mTORC1 inhibitors are the current recommended therapy for SEGA. Nevertheless, a major limitation in the research for SEGA is the lack of cell lines or animal models for mechanistic investigations and development of novel therapy. In this study, we generated TSC1-deficient neural cells from spontaneously immortalized mouse astrocytes in an attempt to mimic human SEGA. The TSC1-deficient cells exhibit mTORC1 hyperactivation and characteristics of transition from astrocytes to neural stem/progenitor cell phenotypes. Rapamycin efficiently decreased mTORC1 activity of these TSC1-deficient cells in vitro. In vivo, TSC1-deficient cells could form SEGA-like tumors and Rapamycin treatment decreased tumor growth. Collectively, our study generates a novel SEGA-like cell line that is invaluable for studying mTORC1-driven molecular and pathological alterations in neurologic tissue. These SEGA-like cells also provide opportunities for the development of novel therapeutic strategy for TSC patients with SEGA.     

PLLA–silver nanoparticles bionanocomposite membranes: Preparation,antibacterial activity,and in vitro hydrolytic degradation assessment

Silver nanoparticles (AgNp) were synthesized in aqueous phase and transferred to chloroform using a fatty amine as phase transfer agent. Poly(l -lactic acid) (PLLA) membranes were prepared using the “functionalized” chloroform. The amount of AgNp in the chloroform was determined by atomic absorption spectroscopy. Thermogravimetric analysis, differential scanning calorimetry, and field emission scanning electron microscopy were used to characterize the membranes. A decrease of the thermal stability of the membranes was observed upon the addition of AgNp; meanwhile, the polymer crystallinity degree increased, making the membranes more fragile and brittle. The in vitro degradation assessments of the membranes in artificial saliva suggested that the time necessary to degrade the PLLA reduced by raising the concentration of the nanostructures. Additionally, the antibacterial assays demonstrated that the addition of only 13 ppm of AgNp were enough to inhibit the formation of biofilm over the bionanocomposite membranes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47998.     

Developing antibacterial surgical adhesives: An enhancement of cyanoacrylate polymers

Surgical site infections (SSIs) and traumatic wounds have a significant risk of becoming contaminated by microbial pathogens of both endogenous and nosocomial origins, including Staphylococcus aureus and Enterococci sp.. One preventative approach is to protect wounds from infection by using a rapidly curing adhesive to seal the wound and prevent further contamination. Here, we demonstrate the covalent incorporation of an antimicrobial, quaternary ammonium chloride monomer (quat) into a 2-octyl cyanoacrylate (2oc) polymer adhesive. Copolymerization was confirmed via nuclear magnetic resonance spectroscopy. Cytotoxicity of the copolymer was assessed against: S. epidermidis and E. coli, and 3T3 mouse fibroblasts. The CA-Quat polymer was found to exhibit dose-dependent bacteriostatic and bactericidal effects against both E. coli and S. epidermidis, importantly without showing any demonstrable toxicity against mammalian 3T3 fibroblast cells. The described experiments provide promising data to suggest successful copolymerization, effective antibacterial properties, and remarkably low cytotoxic effects of the copolymer on mammalian cells.     

Is the Parsonnet''s score a good predictive score of mortality in adult cardiac surgery: assessment by a French multicentre study

Some tumor cells induce platelet aggregation in the bloodstream, which has been implicated in tumor metastasis. In this study, we investigated the mechanism of platelet aggregation induced by a human neuroblastoma cell line, GOTO. It was revealed that GOTO cells had tissue factor on their surface and converted factor X (FX) to FXa with the aid of factor VIIa. The produced FXa formed prothrombinase complex on the cells and activated prothrombin. From experiments on activity inhibition by specific monoclonal as well as polyclonal antibodies, it was concluded that factor V did not constitute this prothrombinase complex. Another cofactor known to constitute prothrombinase complex on some cells, effector cell protease receptor-1 (EPR-1), was not expressed on GOTO cells, suggesting that the cofactor composing FXa-dependent prothrombinase activity on GOTO cells is not factor V or EPR-1 but, rather, is an unknown molecule. Upon the culturing in the presence of 5-bromo-2'-deoxyuridine for 4 days, GOTO cells differentiated into Schwann-like cells, and both FXase and prothrombinase activities were greatly diminished. Flow cytometric analyses revealed that the decrease of FXase activity should be attributed to the decrease of tissue factor expression on GOTO cells. Because these activities greatly diminished upon cellular differentiation, the expression of both cofactor molecules may be related to the malignant and metastatic nature of the tumor cells.     

Medical students' and residents' gender bias in the diagnosis, treatment, and interpretation of coronary heart disease symptoms.

Two competing hypotheses explaining gender bias in cardiac care were tested. The first posits that women's coronary heart disease (CHD) symptoms are simply misinterpreted or discounted. The second posits that women's CHD symptoms are misinterpreted when presented in the context of stress. In two studies, medical students and residents randomized to 2 (male vs. female) × 2 (stress vs. nostress) experiments read vignettes of patients with CHD symptoms and indicated their diagnosis, treatment, and symptom origin interpretation. Both studies disconfirmed the first hypothesis and strongly supported the second. Only when stress was added did women receive significantly lower CHD diagnoses and cardiologist referrals than men and did the origin interpretation of women's CHD symptoms (e.g., chest pain) shift from organic to psychogenic. Neither participants' gender nor their attitude toward women influenced assessments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The further away they are: creative approaches to recording bird flight paths

Abstract

Seeking to model the flight paths of birds as solid objects, this artistic research and development project makes use of digital data collection, computer modelling software and 3-D printing. The project tests notions of objectivity in observation. Eschewing imaginative interpretations of flight, I aspire to allow birds to transcribe their own movements with minimal human intervention. The enquiry began with a drawing process whereby flights were traced by hand on window panes, as they occurred. Subsequent work with the Structure & Motion Lab of the Royal Veterinary College has drawn on high-resolution data from free-flying birds carrying lightweight data loggers. The resulting digital models and 3-D printed models describe short bursts of flight with considerable accuracy. At the same time, the process highlights the impossibility of absolute knowledge and leads to consideration of the need to acknowledge subjectivity – and embrace reciprocity – in observing and recording the natural world.     

Microstructure–Property Correlations in Industrial Thermal Barrier Coatings

This paper describes the results from multidisciplinary characterization/scattering techniques used for the quantitative characterization of industrial thermal barrier coating (TBC) systems used in advanced gas turbines. While past requirements for TBCs primarily addressed the function of insulation/life extension of the metallic components, new demands necessitate a requirement for spallation resistance/strain tolerance, i.e., prime reliance, on the part of the TBC. In an extensive effort to incorporate these TBCs, a design-of-experiment approach was undertaken to develop tailored coating properties by processing under varied conditions. Efforts focusing on achieving durable/high-performance coatings led to dense vertically cracked (DVC) TBCs, exhibiting quasi-columnar microstructures approximating electron-beam physical-vapor-deposited (EB-PVD) coatings. Quantitative representation of the microstructural features in these vastly different coatings is obtained, in terms of porosity, opening dimensions, orientation, morphologies, and pore size distribution, by means of small-angle neutron scattering (SANS) and ultra-small-angle X-ray scattering (USAXS) studies. Such comprehensive characterization, coupled with elastic modulus and thermal conductivity measurements of the coatings, help establish relationships between microstructure and properties in a systematic manner.     

Electronic properties of AlVO<Subscript>4</Subscript> for gas sensor applications

The binary oxide AlVO₄ is being proposed as a new gas sensor material. An X-ray investigation, IR spectrum analysis, resistivity and a calculation of the electronic structure of this compound have been carried out in order to determine its structural, absorptive and sensor properties. The fragment [Al₃V₃O₂₃]¹⁸⁻ is the chain chosen to study the electronic properties of AlVO₄ in the framework of the frontier orbital theory and the interaction between molecules has been described by the Molecular Electrostatic Potential (MEP). The vibration analysis and the simulated infrared spectrum (IR) were calculated for the unit [Al₃V₃O₂₃]¹⁸⁻ and a comparative analysis with the experimental spectrum of AlVO₄ is also presented.     

Rapid Communication: Experimental Evidence that Juvenile Pelagic Jacks (Carangidae) Respond Behaviorally to DMSP

Dimethylsulfoniopropionate (DMSP) is produced by marine algae and released during foraging activity by zooplankton and fish. Pelagic fishes depend on patchily distributed foraging opportunities, and DMSP may be an important signaling molecule for these events. We have previously shown that the abundance of carangid jacks is positively associated with elevated DMSP levels over coral reefs in the Gulf of Mexico, suggesting that these fishes may use spatial and temporal variation in DMSP to locate foraging opportunities. Here, we extend this work by demonstrating that juveniles of two species of pelagic jack, crevalle jack, Caranx hippos, and bluefin trevally, C. melampygus, detect and respond to DMSP in a flow-through tank in the laboratory. Juveniles of these species showed elevated swimming activity in response to ecologically relevant concentrations of DMSP (10⁻⁹ M). These results provide further evidence that this chemical may serve as a chemosensory cue for carangid species.