Risk communication in clinical trials: A cognitive experiment and a survey

10.1186/1472-6947-10-55BMC Medical Informatics and Decision Making101

Targeted CRISPR activation and knockout screenings identify novel doxorubicin transporters

PurposeTissue-specific drug uptake has not been well studied, compared to the deeper understanding of drug resistance mediated by the cellular efflux system such as MDR1 proteins. It has been suggested that many drugs need active or defined transporters to pass the cell membrane. In contrast to efflux components induced after anti-cancer drugs reach the intracellular compartment, drug importers are required for initial drug responses. Furthermore, tissue-specific uptake of anti-cancer drugs may directly impact the side effects of many drugs when they accumulate in healthy tissues. Therefore, linking anti-cancer drugs to their respective drug import transporters would directly help to predict drug responses, whilst minimizing side effects.MethodsTo identify drug transporters of the commonly used anti-cancer drug doxorubicin, we performed focused CRISPR activation and knockout genetic screens targeting all potential membrane-associated transporters and proteins. We monitored the direct uptake of doxorubicin by fluorescence-activated cell sorting (FACS) as the screening readout for identifying transporters/proteins directly involved in doxorubicin uptake.ResultsIntegrating the data from these comprehensive CRISPR screenings, we confirmed previously indicated doxorubicin exporters such as ABCB1 and ABCG2 genes, and identified novel doxorubicin importer gene SLC2A3 (GLUT3). Upregulation of SLC2A3 led to higher doxorubicin uptake and better cell killing, indicating SLC2A3 could be a new marker to predict doxorubicin drug response and minimize side effects for the personalized application of this conventional chemotherapeutic drug.ConclusionsOur study provides a comprehensive way for identifying drug transporters, as exemplified by the commonly used anti-cancer drug doxorubicin. The newly identified importers may have direct clinical implications for the personalized application of doxorubicin in treating distinct tumors. Our results also highlight the necessity of combining both CRISPR knockout and CRISPR activation genetic screens to identify drug transporters.Chemical Immunolog

Effects of Exogenous Cellulase Source on In Vitro Fermentation Characteristics and Methane Production of Crop Straws and Grasses

In vitro fermentation experiments were conducted to investigate the effects of 3 sources of exogenous cellulase products (EC) at 4 dose rates (DR) (0, 12, 37 and 62 IU/g of DM) on degradation of forage and methane production by mixed rumen micro-organisms of goats. The maximum gas production (Vf) of grasses was higher (P<0.001) in Neocallimastix patriciarum (NP) group than those in Trichoderma reesei (TR) and Trichoderma longibrachiatum (TL) groups. Quadratic increases in dry matter degradation (DMD) of forage and neutral detergent fiber (NDFD) of straw were observed for all EC, with optimum DR in the low range. Supplementation of EC originated from TR and NP increased (P<0.001) DMD of forage compared to that from TL. Addition of EC originated from TR and NP also decreased pH value, ammonia nitrogen (NH3-N) and methane (CH4) production compared to that from TL. Quadratic decreases in pH value, NH3-N and CH4 of forage were noted for EC of TR and NP, and with optimum DR in the low range. For short chain fatty acid, the EC of NP increased total volatile fatty acid (TVFA) and acetate concentration and the ratio of acetate to propionate of forage compared with EC of TL and TR, and with optimum DR in the low to medium range. It was concluded that the source of EC differed in fiber degradation and methane emission, and with optimum DR of TR in the low range (from 12 to 37 U/g DM) in improving fiber degradation and decreasing methane emission

Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia

Hand, foot and mouth disease (HFMD) is a prevalent contagious childhood disease typically associated with fever, oral lesions and limb exanthema. While HFMD is caused by a plethora of serotypes of viruses under the genus Enterovirus within the Picornaviridae family, Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are considered the main etiological agents. In recent years however, other viruses have also been isolated in considerable numbers from infected individuals in many regions, joining the legion commonly associated with HFMD. The present study investigated the cytokine and chemokine profiles of HFMD patients from Singapore and Malaysia for the first time. Comparative cohort studies of EV-A71-associated HFMD cases revealed that the Malaysia cohort had a distinct profile from the Singapore cohort, and this could be partly attributed by different EV-A71 genotypes. As the isolation of CV-A6, instead of CV-A16, had become prevalent in the Singapore cohort, it was also of particular interest to study the differential cytokine and chemokine profiles. Our data revealed that overlapping as well as unique profiles exist between the two major causative clinical isolates in the Singapore cohort. Having a better understanding of the respective immunological profiles could be useful for more accurate HFMD diagnosis, which is imperative for disease transmission control until multi-valent vaccines and/or broad-spectrum anti-viral drugs become available

Multimodal Tumor Imaging By Iron Oxides and Quantum Dots Formulated in Poly (Lactic Acid)-D-Alpha-Tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles

Master'sMASTER OF ENGINEERIN

Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-

We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi --> D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7 J/Psi events collected with the BESII detector at the BEPC. No excess of signal above background is observed, and 90% confidence level upper limits on the branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi --> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure

Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar

The branching ratios and Angular distributions for J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure

Chirality of internal metallic and semiconducting carbon nanotubes

We have assigned the chirality of the internal tubes of double walled carbon nanotubes grown by catalytic chemical vapor deposition using the high sensitivity of the radial breathing ~RB! mode in inelastic lightscattering experiments. The deduced chirality corresponds to several semiconducting and only two metallic internal tubes. The RB modes are systematically shifted to higher energies when compared to theoretical values. The difference between experimental and theoretical energies of the RB modes of metallic tubes and semiconducting tubes are discussed in terms of the reduced interlayer distance between the internal and the external tube and electronic resonance effects. We find several pairs of RB modes corresponding to different diameters of internal and external tubes