Homology model of thyroxine binding globulin and elucidation of the thyroid hormone binding site.

The tertiary structure of thyroxine binding globulin (TBG) has been modelled on the basis of its close homology to alpha 1-antitrypsin, the archetype of the serine protease inhibitor (serpin) superfamily. Energy minimization was applied to the model to refine the structure further. The putative thyroid hormone binding region suggested in previous labelling studies was found to exist within a beta-barrel structure of complementary dimensions to the thyroid hormones. The model also revealed that the binding cleft provides the hydrophobic environment and specific ionic interaction sites deemed important for thyroid hormone binding. The model is in good agreement with evidence derived from previously reported T3 and T4 binding, stability and isoelectric focussing studies of TBG and TBG variants. Finally, T4 analogue and drug binding studies have enabled us to postulate the orientation and manner of hormone binding to TBG. This may prove to be of assistance in the development of potent and specific, non-thyroidal ligands and also aid in the understanding of physiological thyroid hormone binding interactions.     

Modelling Infectious Hematopoietic Necrosis Virus Dispersion from Marine Salmon Farms in the Discovery Islands,British Columbia,Canada

Finite volume ocean circulation and particle tracking models are used to simulate water-borne transmission of infectious hematopoietic necrosis virus (IHNV) among Atlantic salmon (Salmo salar) farms in the Discovery Islands region of British Columbia, Canada. Historical simulations for April and July 2010 are carried out to demonstrate the seasonal impact of river discharge, wind, ultra-violet (UV) radiation, and heat flux conditions on near-surface currents, viral dispersion and survival. Numerical particles released from infected farm fish in accordance with IHNV shedding rates estimated through laboratory experiments are dispersed by model oceanic flows. Viral particles are inactivated by ambient UV radiation levels and by the natural microbial community at rates derived through laboratory studies. Viral concentration maps showing temporal and spatial changes are produced and combined with lab-determined minimum infectious dosages to estimate the infective connectivity among farms. Results demonstrate that neighbouring naïve farms can become exposed to IHNV via water-borne transport from an IHNV diseased farm, with a higher risk in April than July, and that many events in the sequence of farm outbreaks in 2001-2002 are consistent with higher risks in our farm connectivity matrix. Applications to other diseases, transfers between farmed and wild fish, and the effect of vaccinations are also discussed.     

Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples

Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.     

Studies on ulcerative dermal necrosis of salmonids

Fourteen fresh run salmon Satmo salar L. with early extant lesions of ulcerative dermal necrosis (UDN) were kept in separate tanks and treated with zinc free malachite green. Ten of the fish were held at 10° C and 4 at 2° C. The treatment precluded infection with Saprolegnia fungus and allowed natural resolution of the lesions. There was a marked difference in rate of healing between warm and cold water conditions.
Histological examination of healing lesions at different stages showed that there was a primary invasion of cuboidal epithelium over the collagen scar followed by a phase of disorganized proliferation which eventually organized itself into normal epithelium. Melanocytes were very obvious in the dermis of healing lesions.     

A New Electrolyte Formulation for Securing High Temperature Cycling and Storage Performances of Na‐Ion Batteries

The Na‐ion battery is recognized as a possible alternative to the Li‐ion battery for applications where power and cost override energy density performance. However, the increasing instability of their electrolyte with temperature is still problematic. Thus, a central question remains how to design Na‐based electrolytes. Here, the discovery of a Na‐based electrolyte formulation is reported which enlists four additives (vinylene carbonate, succinonitrile, 1,3‐propane sultone, and sodium difluoro(oxalate)borate) in proper quantities that synergistically combine their positive attributes to enable a stable solid electrolyte interphase at both negative and positive electrodes surface at 55 °C. Moreover, the role of each additive that consists in producing specific NaF coatings, thin elastomers, sulfate‐based deposits, and so on via combined impedance and X‐ray photoelectron spectroscopy is rationalized. It is demonstrated that empirical electrolyte design rules previously established for Li‐ion technology together with theoretical guidance is vital in the quest for better Na‐based electrolytes that can be extended to other chemistries. Overall, this finding, which is implemented to 18 650 cells, widens the route to the rapid development of the Na‐ion technology based on Na₃V₂(PO₄)₂F₃/C chemistry.