Localized Brain Activation Related to the Strength of Auditory Learning in a Parrot

Parrots and songbirds learn their vocalizations from a conspecific tutor, much like human infants acquire spoken language. Parrots can learn human words and it has been suggested that they can use them to communicate with humans. The caudomedial pallium in the parrot brain is homologous with that of songbirds, and analogous to the human auditory association cortex, involved in speech processing. Here we investigated neuronal activation, measured as expression of the protein product of the immediate early gene ZENK, in relation to auditory learning in the budgerigar (Melopsittacus undulatus), a parrot. Budgerigar males successfully learned to discriminate two Japanese words spoken by another male conspecific. Re-exposure to the two discriminanda led to increased neuronal activation in the caudomedial pallium, but not in the hippocampus, compared to untrained birds that were exposed to the same words, or were not exposed to words. Neuronal activation in the caudomedial pallium of the experimental birds was correlated significantly and positively with the percentage of correct responses in the discrimination task. These results suggest that in a parrot, the caudomedial pallium is involved in auditory learning. Thus, in parrots, songbirds and humans, analogous brain regions may contain the neural substrate for auditory learning and memory

Memory-specific correlated neuronal activity in higher-order auditory regions of a parrot.

Funder: Kayamori Foundation for Informational Science AdvancementFunder: the Netherlands Organization for Scientific ResearchFunder: Multi-Career Path Support Model for Female Researchers project of Japan’s Women UniversityFunder: Japan Society for the Promotion of Science (JSPS) Grant-in-AidFunder: ALW Open Competition and GW Horizon ProgrammeMale budgerigars (Melopsittacus undulatus) are open-ended learners that can learn to produce new vocalisations as adults. We investigated neuronal activation in male budgerigars using the expression of the protein products of the immediate early genes zenk and c-fos in response to exposure to conspecific contact calls (CCs: that of the mate or an unfamiliar female) in three subregions (CMM, dNCM and vNCM) of the caudomedial pallium, a higher order auditory region. Significant positive correlations of Zenk expression were found between these subregions after exposure to mate CCs. In contrast, exposure to CCs of unfamiliar females produced no such correlations. These results suggest the presence of a CC-specific association among the subregions involved in auditory memory. The caudomedial pallium of the male budgerigar may have functional subdivisions that cooperate in the neuronal representation of auditory memory

Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients

The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration-time curve (AUC(0-12)) of everolimus was significantly lower in patients with the NR1I2 8055C/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC(0-12) of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC(0-12). Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C>T polymorphism before administration

Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation. Significant correlations between the AUC/D of tacrolimus and everolimus were found for patients with the CYP3A5*1 allele or CYP3A5*3/*3 at both one month and one year. At both stages, the determination coefficients were higher and the slopes of regression equations were larger for patients with CYP3A5*3/*3 compared to the CYP3A5*1 allele. A good correlation between single doses of tacrolimus and everolimus was found for CYP3A5*3/*3 patients at 1 year after transplantation (r = 0.794, p < 0.001). The variability of the AUC0–24/D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC0–12/D of everolimus. Clinicians may be able to comprehensively carry out the dose adjustments of tacrolimus and everolimus based on relationship with AUCs of both drugs in each CYP3A5 genotype

Prognostic value of plasminogen activator inhibitor-1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib

Background and AimsVascular endothelial growth factor-directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers. MethodsFrom September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4weeks after axitinib initiation. Bio-Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation. ResultsPatients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor-1 (PAI-1) level from pre-treatment to 4weeks after axitinib initiation compared with those with progressive disease (P = .022). The median progression-free survival (PFS) and median overall survival (OS) in patients with increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation were significantly shorter than those with decreased serum PAI-1 level (P = .027 and P = .026, respectively). Increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses (P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI-1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis (P = .026 and P = .010, respectively). ConclusionsThe initial change in serum PAI-1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC

Sex-inducing effects toward planarians widely present among parasitic flatworms

Summary Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.journal articl

2006ネン ニ トクシマシ シロヤマ ニ ショクジュ サレタ ホルトノキ ノ ナエギ ノ ゲンジョウ : セイイク ジョウキョウ ト ホルトノキ イオウビョウ カンセン ジョウキョウ ニツイテ

Elaeocarpus zollingeri (synonym: E. sylvestris) was one of dominant trees in Mt. Shiroyama in the Tokushima City until 1970s, however, most of adult trees have died by Elaeocarpus yellows. To prevent extinction 300 nursery trees were planted at the foot of the mountain by local volunteers in 2006. In this study we investigated their survival, growth, and infection status of the disease. We found 40 nursery trees have survived (survival rate was 13%). Survived trees were abundant in areas facing the south, and most trees disappeared in areas facing the north and the west. Growth of the trees was well also in areas facing the south. Among the survived 40 nursery trees, we found three trees infected with phytoplasma, the pathogen of Elaeocarpus yellows, based on PCR analysis. It is not clear when they were infected with phytoplasma, whether they have infected after the plantation or they already had phytoplasma in the seed. Anyway, the fact that only a few tree is infected must be gratifying in considering the conservation E. zollinger in Mt. Shiroyama

Genetic Predisposition to Ischemic Stroke

Background and Purpose—The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk.Methods—We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets).Results—In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001).Conclusions—The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors