Evaluation of cognitive function in adult rhesus monkeys using the finger maze test

In research on cognitive function, the use of experimental animals is essential for the study of human cognitive processes and mechanisms. Furthermore, non-human primates are necessary for understanding higher cognitive functions in humans. However, there are few cognitive function tests available for non-human primates, Thus, we modified a finger maze test for application to non-human primates. In this study, we assessed learning and memory in 12 adult rhesus monkeys using a finger maze test that was developed to assess cognitive functions in captive non-human primates. The monkeys were trained with moving rewards indicating the correct direction, which allowed the monkeys to obtain the reward. Following training, subjects completed a learning trial and a memory trial two months later. Although the time required for training varied among the monkeys, 11 out of 12 monkeys completed the training and achieved a high success rate in the learning trial as well as in the memory trial conducted 2 months later. This is the first study to apply the finger maze test to adult rhesus monkeys. The finger maze test enabled us to assess learning and memory in several adult rhesus monkeys simultaneously

Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases

BACKGROUND: Despite aggressive treatment with radiation therapy and concurrent adjuvant temozolomide (TMZ), glioblastoma multiform (GBM) still has a dismal prognosis. We aimed to identify strategies to improve the therapeutic outcome of combined radiotherapy and TMZ in GBM by targeting pro-survival signaling from the epidermal growth factor receptor (EGFR). METHODS: Glioma cell lines U251, T98G were used. Colony formation, DNA damage repair, mode of cell death, invasion, migration and vasculogenic mimicry as well as protein expression were determined. RESULTS: U251 cells showing a low level of methyl guanine transferase (MGMT) were highly responsive to the radiosensitizing effect of TMZ compared to T98G cells having a high level of MGMT. Treatment with a dual inhibitor of Class I PI3K/mTOR, PI103; a HSP90 inhibitor, 17-DMAG; or a HDAC inhibitor, LBH589, further increased the cytotoxic effect of radiation therapy plus TMZ in U251 cells than in T98G cells. However, treatment with a mTOR inhibitor, rapamycin, did not discernibly potentiate the radiosensitizing effect of TMZ in either cell line. The mechanism of enhanced radiosensitizing effects of TMZ was multifactorial, involving impaired DNA damage repair, induction of autophagy or apoptosis, and reversion of EMT (epithelial-mesenchymal transition). CONCLUSIONS: Our results suggest possible strategies for counteracting the pro-survival signaling from EGFR to improve the therapeutic outcome of combined radiotherapy and TMZ for high-grade gliomas

Slow Control Systems of the Reactor Experiment for Neutrino Oscillation

The RENO experiment has been in operation since August 2011 to measure reactor antineutrino disappearance using identical near and far detectors. For accurate measurements of neutrino mixing parameters and efficient data taking, it is crucial to monitor and control the detector in real time. Environmental conditions also need to be monitored for stable operation of detectors as well as for safety reasons. In this article, we report the design, hardware, operation, and performance of the slow control system

Gene expression links functional networks across cortex and striatum

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease

Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Background Despite aggressive treatment with radiation therapy and concurrent adjuvant temozolomide (TMZ), glioblastoma multiform (GBM) still has a dismal prognosis. We aimed to identify strategies to improve the therapeutic outcome of combined radiotherapy and TMZ in GBM by targeting pro-survival signaling from the epidermal growth factor receptor (EGFR). Methods Glioma cell lines U251, T98G were used. Colony formation, DNA damage repair, mode of cell death, invasion, migration and vasculogenic mimicry as well as protein expression were determined. Results U251 cells showing a low level of methyl guanine transferase (MGMT) were highly responsive to the radiosensitizing effect of TMZ compared to T98G cells having a high level of MGMT. Treatment with a dual inhibitor of Class I PI3K/mTOR, PI103; a HSP90 inhibitor, 17-DMAG; or a HDAC inhibitor, LBH589, further increased the cytotoxic effect of radiation therapy plus TMZ in U251 cells than in T98G cells. However, treatment with a mTOR inhibitor, rapamycin, did not discernibly potentiate the radiosensitizing effect of TMZ in either cell line. The mechanism of enhanced radiosensitizing effects of TMZ was multifactorial, involving impaired DNA damage repair, induction of autophagy or apoptosis, and reversion of EMT (epithelial-mesenchymal transition). Conclusions Our results suggest possible strategies for counteracting the pro-survival signaling from EGFR to improve the therapeutic outcome of combined radiotherapy and TMZ for high-grade gliomas

Cross-Linking Amine-Rich Compounds into High Performing Selective CO2 Absorbents

Amine-based absorbents play a central role in CO2 sequestration and utilization. Amines react selectively with CO2, but a drawback is the unproductive weight of solvent or support in the absorbent. Efforts have focused on metal organic frameworks (MOFs) reaching extremely high CO2 capacity, but limited selectivity to N2 and CH4, and decreased uptake at higher temperatures. A desirable system would have selectivity (cf. amine) and high capacity (cf. MOF), but also increased adsorption at higher temperatures. Here, we demonstrate a proof-of-concept where polyethyleneimine (PEI) is converted to a high capacity and highly selective CO2 absorbent using buckminsterfullerene (C60) as a cross-linker. PEI-C60 (CO2 absorption of 0.14 g/g at 0.1 bar/90°C) is compared to one of the best MOFs, Mg-MOF-74 (0.06 g/g at 0.1 bar/90°C), and does not absorb any measurable amount of CH4 at 50 bar. Thus, PEI-C60 can perform better than MOFs in the sweetening of natural gas

Percutaneous coronary intervention in asians- are there differences in clinical outcome?

<p>Abstract</p> <p>Background</p> <p>Ethnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD).</p> <p>Methods</p> <p>A prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months.</p> <p>Results</p> <p>7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients.</p> <p>Conclusion</p> <p>These data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.</p

Measurement of cosmogenic 9^9Li and 8^8He production rates at RENO

We report the measured production rates of unstable isotopes $^9$Li and $^8$He produced by cosmic muon spallation on $^{12}$C using two identical detectors of the RENO experiment. Their beta-decays accompanied by a neutron make a significant contribution to backgrounds of reactor antineutrino events in precise determination of the smallest neutrino mixing angle. The mean muon energy of its near (far) detector with an overburden of 120 (450) m.w.e. is estimated as 33.1 +- 2.3 (73.6 +- 4.4) GeV. Based on roughly 3100 days of data, the cosmogenic production rate of $^9$Li ($^8$He) isotope is measured to be 44.2 +- 3.1 (10.6 +- 7.4) per day at near detector and 10.0 +- 1.1 (2.1 +- 1.5) per day at far detector. This corresponds to yields of $^9$Li ($^8$He), 4.80 +- 0.36 (1.15 +- 0.81) and 9.9 +- 1.1 (2.1 +- 1.5) at near and far detectors, respectively, in a unit of 10$^{-8}$ $\mu^{-1}$ g${^-1}$ cm${^2}$. Combining the measured $^9$Li yields with other available underground measurements, an excellent power-law relationship of the yield with respect to the mean muon energy is found to have an exponent of $\alpha$ = 0.76 +- 0.05.Comment: 11 pages, 14 figure