Biliary excretion of certain bile acids is mediated by multidrug resistance associated protein 2 (Mrp2) and the bile salt export pump (Bsep). In the present study, the transport properties of several bile acids were characterized in canalicular membrane vesicles (CMVs) isolated from Sprague--Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBR) whose Mrp2 function is hereditarily defective and in membrane vesicles isolated from Sf9 cells infected with recombinant baculovirus containing cDNAs encoding Mrp2 and Bsep. ATP-dependent uptake of [(3)H]taurochenodeoxycholate sulfate (TCDC-S) (K(m)=8.8 microM) and [(3)H]taurolithocholate sulfate (TLC-S) (K(m)=1.5 microM) was observed in CMVs from SD rats, but not from EHBR. In addition, ATP-dependent uptake of [(3)H]TLC-S (K(m)=3.9 microM) and [(3)H]taurocholate (TC) (K(m)=7.5 microM) was also observed in Mrp2- and Bsep-expressing Sf9 membrane vesicles, respectively. TCDC-S and TLC-S inhibited the ATP-dependent TC uptake into CMVs from SD rats with IC(50) values of 4.6 microM and 1.2 microM, respectively. In contrast, the corresponding values for Sf9 cells expressing Bsep were 59 and 62 microM, respectively, which were similar to those determined in CMVs from EHBR (68 and 33 microM, respectively). By co-expressing Mrp2 with Bsep in Sf9 cells, IC(50) values for membrane vesicles from these cells shifted to values comparable with those in CMVs from SD rats (4.6 and 1.2 microM). Moreover, in membrane vesicles where both Mrp2 and Bsep are co-expressed, preincubation with the sulfated bile acids potentiated their inhibitory effect on Bsep-mediated TC transport. These results can be accounted for by assuming that the sulfated bile acids trans-inhibit the Bsep-mediated transport of TC.

in 4 regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic. Conclusions Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, that facilitate greater scale and spread of telepsychiatry globally.

During courtship, many animals, including insects, birds, fish, and mammals, utilize acoustic signals to transmit information about species identity. Although auditory communication is crucial across phyla, the neuronal and physiologic processes are poorly understood. Sound-evoked chaining behavior, a display of homosexual courtship behavior in Drosophila males, has long been used as an excellent model for analyzing auditory behavior responses, outcomes of acoustic perception and higher-order brain functions. Here we developed a new method, termed ChaIN (Chain Index Numerator), in which we use a computer-based auto detection system for chaining behavior. The ChaIN system can systematically detect the chaining behavior induced by a series of modified courtship song playbacks. Two evolutionarily related Drosophila species, Drosophila melanogaster and Drosophila simulans, exhibited dramatic selective increases in chaining behavior when exposed to specific auditory cues, suggesting that auditory discrimination processes are involved in the acceleration of chaining behavior. Prolonged monotonous pulse sounds containing courtship song components also induced high intense chaining behavior. Interestingly, the chaining behavior was gradually suppressed over time when song playback continued. This behavioral change is likely to be a plastic behavior and not a simple sensory adaptation or fatigue, because the suppression was released by applying a different pulse pattern. This behavioral plasticity is not a form of habituation because different modality stimuli did not recover the behavioral suppression. Intriguingly, this plastic behavior partially depended on the cAMP signaling pathway controlled by the rutabaga adenylyl cyclase gene that is important for learning and memory. Taken together, this study demonstrates the selectivity and behavioral kinetics of the sound-induced interacting behavior of Drosophila males, and provides a basis for the systematic analysis of genes and neural circuits underlying complex acoustic behavior.

Drugs have multiple, not single, effects. Decomposition of drug effects into basic components helps us to understand the pharmacological properties of a drug and contributes to drug discovery. We have extended factor analysis and developed a novel profile data analysis method: orthogonal linear separation analysis (OLSA). OLSA contracted 11,911 genes to 118 factors from transcriptome data of MCF7 cells treated with 318 compounds in a Connectivity Map. Ontology of the main genes constituting the factors detected significant enrichment of the ontology in 65 of 118 factors and similar results were obtained in two other data sets. In further analysis of the Connectivity Map data set, one factor discriminated two Hsp90 inhibitors, geldanamycin and radicicol, while clustering analysis could not. Doxorubicin and other topoisomerase inhibitors were estimated to inhibit Na+/K+ ATPase, one of the suggested mechanisms of doxorubicin-induced cardiotoxicity. Based on the factor including PI3K/AKT/mTORC1 inhibition activity, 5 compounds were predicted to be novel inducers of autophagy, and other analyses including western blotting revealed that 4 of the 5 actually induced autophagy. These findings indicate the potential of OLSA to decompose the effects of a drug and identify its basic components.