One-step synthesis of biodegradable curcumin-derived hydrogels as potential soft tissue fillers after breast cancer surgery

A one-step synthesis of a curcumin-derived hydrogel (curcumin content of 25-75 mol %) is reported. Curcumin is incorporated into the hydrogel backbone and cross-linked through biodegradable carbonate linkages. Curcumin as a part of the polymer backbone is protected from oxidation and degradation, while hydrogel hydrolysis results in the release of active curcumin. Nontoxic poly(ethylene glycol) and desaminotyrosyl-tyrosine ethyl ester are used to tune the hydrophilic/hydrophobic hydrogel properties. In this way, hydrogels with a wide range of physical properties including water-uptake (100-550%) and compression moduli (7-100 kPa) were obtained. Curcumin release is swelling-controlled and could be extended to 80 days. In vitro, curcumin-derived hydrogels showed selective cytotoxicity against MDA-MB-231 (IC(50) 9 μM) breast cancer cells but no cytotoxicity to noncancerous quiescent human dermal fibroblasts even at high curcumin concentrations (160 μM). One possible application of these curcumin-derived hydrogels is as soft tissue filler after surgical removal of cancerous tissue.     

Salmon aquaculture and antimicrobial resistance in the marine environment

Antimicrobials used in salmon aquaculture pass into the marine environment. This could have negative impacts on marine environmental biodiversity, and on terrestrial animal and human health as a result of selection for bacteria containing antimicrobial resistance genes. We therefore measured the numbers of culturable bacteria and antimicrobial-resistant bacteria in marine sediments in the Calbuco Archipelago, Chile, over 12-month period at a salmon aquaculture site approximately 20 m from a salmon farm and at a control site 8 km distant without observable aquaculture activities. Three antimicrobials extensively used in Chilean salmon aquaculture (oxytetracycline, oxolinic acid, and florfenicol) were studied. Although none of these antimicrobials was detected in sediments from either site, traces of flumequine, a fluoroquinolone antimicrobial also widely used in Chile, were present in sediments from both sites during this period. There were significant increases in bacterial numbers and antimicrobial-resistant fractions to oxytetracycline, oxolinic acid, and florfenicol in sediments from the aquaculture site compared to those from the control site. Interestingly, there were similar numbers of presumably plasmid-mediated resistance genes for oxytetracycline, oxolinic acid and florfenicol in unselected marine bacteria isolated from both aquaculture and control sites. These preliminary findings in one location may suggest that the current use of large amounts of antimicrobials in Chilean aquaculture has the potential to select for antimicrobial-resistant bacteria in marine sediments.     

Molecular Epidemiology of Influenza A(H1N1)pdm09 Viruses from Pakistan in 2009-2010

Background

In early 2009, a novel influenza A(H1N1) virus that emerged in Mexico and United States rapidly disseminated worldwide. The spread of this virus caused considerable morbidity with over 18000 recorded deaths. The new virus was found to be a reassortant containing gene segments from human, avian and swine influenza viruses.

Methods/Results

The first case of human infection with A(H1N1)pdm09 in Pakistan was detected on 18^th June 2009. Since then, 262 laboratory-confirmed cases have been detected during various outbreaks with 29 deaths (as of 31^st August 2010). The peak of the epidemic was observed in December with over 51% of total respiratory cases positive for influenza. Representative isolates from Pakistan viruses were sequenced and analyzed antigenically. Sequence analysis of genes coding for surface glycoproteins HA and NA showed high degree of high levels of sequence identity with corresponding genes of regional viruses circulating South East Asia. All tested viruses were sensitive to Oseltamivir in the Neuraminidase Inhibition assays.

Conclusions

Influenza A(H1N1)pdm09 viruses from Pakistan form a homogenous group of viruses. Their HA genes belong to clade 7 and show antigenic profile similar to the vaccine strain A/California/07/2009. These isolates do not show any amino acid changes indicative of high pathogenicity and virulence. It is imperative to continue monitoring of these viruses for identification of potential variants of high virulence or drug resistance.     

Metabolic state and cell cycle as determinants of facilitated uptake of genetic information by yeast <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

The transformation efficiency of yeast cells during exponential growth might be characterised as undulatory. The aim of the study was to investigate the reason for the fluctuation in transformation efficiency of yeast Saccharomyces cerevisiae p63-DC5 cells during exponential growth. The heightened response to exogenous DNA was observed with the growing yeast culture when budded cells were predominant. To confirm this phenomenon we carried out synchronization of yeast cells with 10 mM hydroxyurea. Results showed that synchronous yeast cells in the S-phase of cell cycle have enhanced transformation efficiency. Furthermore, S. cerevisiae p63-DC5 cells in the S-phase were successfully transformed with plasmid pl13 in the absence of lithium acetate. We indicated that the permeability of yeast cells in the S-phase to tetraphenylphosphonium (TPP) cations was significantly higher than in asynchronous culture. The results of our study showed that the fluctuation in transformation efficiency was strictly dependent on the metabolic state of yeast cells and the capacity of the yeast cells to become competent was related to the S-phase of cell cycle.     

GIS and Remote Sensing for Detecting Yield Loss in Cranberry Culture

The primary goal of our research is to develop key elements of a precision agriculture program applicable to high-value woody perennial crops, such as cranberries. These crop systems exhibit tremendous variability in crop yields and quality as imposed by variations in soil properties (water availability and nutrient deficiency) that lead to crop stress (disease development and weed competition). Some of the variability present in the growing environment results in persistent yield losses as well as crop-quality reductions. We are using state-of-the-art methodologies (GIS, GPS, remote sensing) to identify and map spatial variations of the crop. Through image-processing methods (NDVI and unsupervised classification), approximately 65% of the variation in yield was described using 4-m multispectral satellite data as a base image.     

The mantle, ink sac, ink, arm hooks and soft body debris associated with the shells in Late Triassic coleoid cephalopod Phragmoteuthis from the Austrian Alps

Fragmentarily preserved shells – mainly pro-ostraca, in several cases also phragmocones – occurring together with arm hooks and the ink sac of the Carnian (Late Triassic) coleoid cephalopod Phragmoteuthis bisinuata (Bronn) from Lunz (Austria) are examined with the scanning electron microscope and energy-dispersive spectrometer. The pro-ostracum bears black, shiny, pitch-like sheets. The black sheets, the ink sac content and the arm hooks have a granular ultrastructure of 0.1–1 μm grain size. The arm hooks and black sheets are micro-laminated; each lamina consists of fibres. The ink consists of an agglomerate of grains. On the ventral (internal) side of the pro-ostracum, the black sheets occasionally bear agglomerates of homogeneous, ink-like material along with heterogeneous structures. The pro-ostracum has crystal-shaped units with lamello-columnar ultrastructure of the inner layer and plate ultrastructure of the outer layer. This resembles the Late Triassic Lunzoteuthis [Doguzhaeva, L.A., Mutvei, H., Summesberger, H., 2005a. A Late Triassic coleoid from the Austrian Alps: the pro-ostracum viewpoint. In: Kostak, M., Marek, J. (Eds.), Proceedings of the 2nd International Symposium on Coleoid Cephalopods Through Time. Short Papers/Abstracts Vol. Prague, 26–29 September, 2005, pp. 55–59] and Early Jurassic Belemnotheutis [Doguzhaeva, L.A., Donovan, D.T., Mutvei, H., 2005b. The rostrum, conotheca and pro-ostracum in the Jurassic coleoid Belemnotheutis Pearce from Wiltshire, England. In: Kostak, M., Marek, J. (Eds.), Proceedings of the 2nd International Symposium on Coleoid Cephalopods Through Time. Short Papers/Abstracts Vol. Prague, 26–29 September, 2005, pp. 45–49]. The black sheets, the material on their inner surface, the ink and the arm hooks consist of carbon, occasionally with minor amounts of sulfur. The shell is of calcium carbonate.Based on their organic composition, position in the shell and lamello-fibrillar ultrastructure, the black sheets are considered to be remains of the mantle, sometimes with ink sac and soft body debris. The carbon composition and granular ultrastructure of arm hooks, ink, and soft tissue remains indicate that the non-mineralized structures are pseudomorphosed by carbon (carbonization), possibly due to C-accumulating bacteria.     

Distribution of legionellae in a hospital water system: prevalence of immunologically and genetically related Legionella pneumophila serogroup 6 isolates

A hospital warm water system was monitored for the presence and distribution of legionellae. Subtyping of ten selected Legionella pneumophila isolates, originating from four different sites in the system by using serogroup specific antisera in an indirect immunofluorescence test, revealed that nine of the ten isolates belong to serogroup 6, while the remaining one was serogroup 10. Two monoclonal antibodies (mAbs) specific for a subgroup of serogroup 6 strains were further used for characterization. None of the strains reacted with these mAbs. Genome analysis by elaborating NotI profiles using the pulsed field gel electrophoresis (PFGE) technique revealed that nearly all serogroup 6 isolates derived from different sites, including a new building connected by a ring pipe, were identical according to restriction fragment patterns. The patterns were distinguishable from those of the two L. pneumophila serogroup 6 reference strains, and from that of the L. pneumophila serogroup 10 isolate. These data argue for a relatively homogeneous L. pneumophila serogroup 6 population in the entire water system.     

Synthesis,molecular docking,and biological activity of 2-vinyl chromones: Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's disease therapeutics

We investigated the biological activity of a series of substituted chromeno[3,2-c]pyridines, including compounds previously synthesized by our group and novel compounds whose syntheses are reported here. Tandem transformation of their tetrahydropyridine ring under the action of activated alkynes yielding 2-vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of a biologically active chromone system. The inhibitory activity of these chromone derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and molecular docking. Antioxidant (antiradical) activity of the compounds was assessed in the ABTS assay. The results demonstrated that a subset of the studied chromone derivatives selectively inhibit BChE but do not exhibit antiradical activity. In addition, the results of molecular docking effectively explained the observed features in the efficacy, selectivity, and mechanism of BChE inhibition by the chromone derivatives.     

A membrane fusion protein,Ykt6, regulates epithelial cell migration via microRNA-mediated suppression of Junctional Adhesion Molecule A

Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven by soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, is an essential step of vesicle trafficking. Mammalian SNAREs represent a large group of proteins, but few have been implicated in the regulation of cell migration. Ykt6 is a unique SNARE existing in equilibrium between active membrane-bound and inactive cytoplasmic pools, and mediating vesicle trafficking between different intracellular compartments. The biological functions of this protein remain poorly understood. In the present study, we found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulates the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. This decreased JAM-A expression limits the activity of Rap1 and Rac1 small GTPases, thereby attenuating cell spreading and motility. The described novel functions of Ykt6 could be essential for the regulation of epithelial barriers, epithelial repair, and metastatic dissemination of cancer cells.