Taste sorting and naming: can taste concepts be misrepresented by traditional psychophysical labelling systems?

Japanese and American subjects were required to sort filterpapers, soaked in taste stimuli, into categories that had conceptuallythe same taste. Both Japanese and Americans sorted in the samemanner, indicating similar conceptualization. Taste names weregiven to the taste categories obtained by using the traditional‘four basic taste’ naming system, common in tastepsychophysics. This method was seen to underestimate the numberof categories actually present. This suggests a re-assessmentof current psychophysical taste-naming techniques.     

Composite origin of major histocompatibility complex genes

Major histocompatibility complex WHO genes have now been cloned from representatives of all vertebrate classes except Agnatha. The recent accumulation of sequence data has given great insight into the course of evolution of these genes. Although the primary structure of the MHC genes varies greatly from class to class and also within the individual classes, the general features of the tertiary and quaternary structure have been conserved remarkably well during more than 400 million years.of evolution. The ancestral MHC genes may have been assembled from at least three structural elements derived from different gene families. Class II MHC genes appear to have been assembled first, and then to have given rise to class I genes.     

Analysis of chemometric models applied to Raman spectroscopy for monitoring key metabolites of cell culture

The Food and Drug Administration (FDA) initiative of Process Analytical Technology (PAT) encourages the monitoring of biopharmaceutical manufacturing processes by innovative solutions. Raman spectroscopy and the chemometric modeling tool partial least squares (PLS) have been applied to this aim for monitoring cell culture process variables. This study compares the chemometric modeling methods of Support Vector Machine radial (SVMr), Random Forests (RF), and Cubist to the commonly used linear PLS model for predicting cell culture components—glucose, lactate, and ammonia. This research is performed to assess whether the use of PLS as standard practice is justified for chemometric modeling of Raman spectroscopy and cell culture data. Model development data from five small-scale bioreactors (2 × 1 L and 3 × 5 L) using two Chinese hamster ovary (CHO) cell lines were used to predict against a manufacturing scale bioreactor (2,000 L). Analysis demonstrated that Cubist predictive models were better for average performance over PLS, SVMr, and RF for glucose, lactate, and ammonia. The root mean square error of prediction (RMSEP) of Cubist modeling was acceptable for the process concentration ranges of glucose (1.437 mM), lactate (2.0 mM), and ammonia (0.819 mM). Interpretation of variable importance (VI) results theorizes the potential advantages of Cubist modeling in avoiding interference of Raman spectral peaks. Predictors/Raman wavenumbers (cm⁻¹) of interest for individual variables are X1139–X1141 for glucose, X846–X849 for lactate, and X2941–X2943 for ammonia. These results demonstrate that other beneficial chemometric models are available for use in monitoring cell culture with Raman spectroscopy.     

Magnetic core-shell nanoparticles for drug delivery by nebulization

Background

Aerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe₃O₄ magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.

Results

Average particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 μg/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.

Conclusion

We have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route.     

Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.     

The diet of Little Owls Athene noctua in Gloucestershire,England

Capsule Little Owls take a wide variety of food, most of which is made up of earthworms, but also includes bats.     

Opt-Out Panel Testing for HIV,Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study

Objectives

Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.

Methods

An opt-out ED blood borne virus screening programme was piloted from March 2014 to January 2015. Patients undergoing blood sampling during routine clinical care were offered HIV 1&2 antibody/antigen assay, HBV surface antigen and HCV antibody tests. Linkage to care where necessary was co-ordinated by the study team. New diagnosis and prevalence rates were defined as the new cases per 1000 tested and number of positive tests per 1000 tested respectively.

Results

Over 45 weeks of testing, of 10,000 patient visits, 8,839 individual patient samples were available for analysis following removal of duplicates. A sustained target uptake of >50% was obtained after week 3. 97(1.09%), 44(0.49%) and 447(5.05%) HIV, Hepatitis B and Hepatitis C tests were positive respectively. Of these, 7(0.08%), 20(0.22%) and 58(0.66%) were new diagnoses of HIV, Hepatitis B and Hepatitis C respectively. The new diagnosis rate for HIV, Hepatitis B and Hepatitis C was 0.8, 2.26 and 6.5 per 1000 and study prevalence for HIV, Hepatitis B and Hepatitis C was 11.0, 5.0 and 50.5 per 1000 respectively.

Conclusions

Opt-out blood borne viral screening was feasible and acceptable in an inner-city ED. Blood borne viral infections were prevalent in this population and newly diagnosed cases were diagnosed and linked to care. These results suggest widespread blood borne viral testing in differing clinical locations with differing population demographic risks may be warranted.     

Differential responses by two closely related native fishes to restoration actions

Globally, river degradation has decimated freshwater fish populations. To help reverse this trend in a southeastern Australia river, we used multiple restoration actions, including reintroduction of instream woody habitat, riparian revegetation, removal of a weir hindering fish movement, fencing out livestock, and controlling riparian weeds. We monitored the responses of native fish at the segment scale (20 km) and reach scale (0.3 km) over 7 years to assess the effectiveness of the different restoration strategies. Two closely related species, Murray cod Maccullochella peeli and trout cod Maccullochella macquariensis, increased at the restored segment compared with the control segment. However, inherent differences between river segments and low sample size hampered assessment of the mechanisms responsible for segment‐scale changes in fish abundance. In contrast, at the reach scale, only M. peeli abundance significantly increased in reaches supplemented with wood. These differential responses by 2 closely related fish species likely reflect species‐specific responses to increased habitat availability and enhanced longitudinal connectivity when the weir improved passage around a fishway. Changes in M. peeli abundance in segments supplemented with and without wood suggest an increase in carrying capacity and not simply a redistribution of individuals within the segment, facilitated the observed expansion. Our findings confirm the need to consider individual fish species' habitat preferences carefully when designing restoration interventions. Further, species‐specific responses to restoration actions provide waterway managers with precise strategies to target fish species for recovery and the potential to predict fish outcomes based on ecological preferences.