Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons

Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep

Electrical reliability and leakage mechanisms in highly resistive multiferroic La0.1Bi0.9FeO3 ceramics

Multiferroic La0.1 Bi0.9 FeO3 (LBFO) ceramics with high resistivity were synthesized by using a modified rapid thermal process. The LBFO ceramics show very low leakage and low dielectric loss. Well saturated ferroelectric hysteresis loops and polarization switching currents have been observed. For a maximum applied electric field of 145 kV/cm, the remanent polarization is 17.8 μC/ cm2 and the coercive filed is 75 kV/cm. The dominant conduction mechanism in the LBFO ceramics has been found to be the space-charge-limited current mechanism rather than the thermal excitation mechanism. Electrical reliability related to the fatigue and polarization retention of the LBFO ceramics has also been discussed with the leakage mechanisms. © 2011 American Institute of Physics.published_or_final_versio

Increased expression of cyclooxygenase-2 in first-degree relatives of gastric cancer patients

Aim: To study the expression of cyclooxygenase-2 (COX-2) in human gastric cancer tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum and corpus of the first-degree relatives of the recruited cancer patients. Methods: The expression of COX-2 mRNA in 38 patients with gastric cancer and their 29 first-degree relatives and 18 healthy controls was assessed by the real time RT-PCR. The expression of COX-2 protein was determined by Western blot. Results: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%) cancerous tissues compared to their respective paired normal mucosa (P<0.001). Interestingly, increased COX-2 mRNA expression was also found in mucosa of the corpus (6/29) and antrum (13/29) of their first-degree relatives. Increased COX-2 mRNA expression was more frequently observed in the antrum biopsies from cancer patients than in the antrum biopsies from healthy controls (P<0.05). In addition, 3 of 23 (13%) patients with atrophic mucosa and 6 of 35 (17%) patients with intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2 expression increased in H pylori-positive tissues, especially in antrum mucosa. Conclusion: Increased COX-2 expression is involved in gastric carcinogenesis, and may be necessary for maintenance of the malignant phenotype and contribute to Helicobacter pylori-associated malignant transformation. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Resistive switching and threshold switching behaviors in La 0.1Bi 0.9Fe 1-xCo xO 3 ceramics

The effects of cobalt doping on the electrical conductivity of La 0.1Bi 0.9Fe 1-xCo xO 3 (LBFCO, x=0, 0.01, 0.03) ceramics were investigated. It is found that the leakage current increases with cobalt dopant concentration in LBFCO. On the application of bias voltage LBFCO ceramics with cobalt doping exhibits resistive switching effects at room temperature and threshold switching effects at elevated temperatures (50°C and 80°C). X-ray photoelectron spectroscopy of LBFCO ceramics show that cobalt dopant is bivalent as an acceptor, which induces an enhancement of oxygen vacancy concentration in LBFCO ceramics. Possible mechanisms for both resistive switching and threshold switching effects are discussed on the basis of the interplay of bound ferroelectric charges and mobile charged defects. © 2012 American Institute of Physics.published_or_final_versio

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

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Self-administered acupressure for symptom management among Chinese family caregivers with caregiver stress: a randomized, wait-list controlled trial

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Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes

Introduction: In recent years, there has been an exponential increase in the number of studies aiming to understand the biology of exosomes, as well as other extracellular vesicles. However, classification of membrane vesicles and the appropriate protocols for their isolation are still under intense discussion and investigation. When isolating vesicles, it is crucial to use systems that are able to separate them, to avoid cross-contamination. Method: EVs released from three different kinds of cell lines: HMC-1, TF-1 and BV-2 were isolated using two centrifugation-based protocols. In protocol 1, apoptotic bodies were collected at 2,000&#x00D7;g, followed by filtering the supernatant through 0.8 &#x00B5;m pores and pelleting of microvesicles at 12,200&#x00D7;g. In protocol 2, apoptotic bodies and microvesicles were collected together at 16,500&#x00D7;g, followed by filtering of the supernatant through 0.2 &#x00B5;m pores and pelleting of exosomes at 120,000&#x00D7;g. Extracellular vesicles were analyzed by transmission electron microscopy, flow cytometry and the RNA profiles were investigated using a Bioanalyzer&#x00AE;. Results: RNA profiles showed that ribosomal RNA was primary detectable in apoptotic bodies and smaller RNAs without prominent ribosomal RNA peaks in exosomes. In contrast, microvesicles contained little or no RNA except for microvesicles collected from TF-1 cell cultures. The different vesicle pellets showed highly different distribution of size, shape and electron density with typical apoptotic body, microvesicle and exosome characteristics when analyzed by transmission electron microscopy. Flow cytometry revealed the presence of CD63 and CD81 in all vesicles investigated, as well as CD9 except in the TF-1-derived vesicles, as these cells do not express CD9. Conclusions: Our results demonstrate that centrifugation-based protocols are simple and fast systems to distinguish subpopulations of extracellular vesicles. Different vesicles show different RNA profiles and morphological characteristics, but they are indistinguishable using CD63-coated beads for flow cytometry analysis

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual residual fluid intelligence scores from cortical grey matter morphology

We predicted residual fluid intelligence scores from T1-weighted MRI data available as part of the ABCD NP Challenge 2019, using morphological similarity of grey-matter regions across the cortex. Individual structural covariance networks (SCN) were abstracted into graph-theory metrics averaged over nodes across the brain and in data-driven communities/modules. Metrics included degree, path length, clustering coefficient, centrality, rich club coefficient, and small-worldness. These features derived from the training set were used to build various regression models for predicting residual fluid intelligence scores, with performance evaluated both using cross-validation within the training set and using the held-out validation set. Our predictions on the test set were generated with a support vector regression model trained on the training set. We found minimal improvement over predicting a zero residual fluid intelligence score across the sample population, implying that structural covariance networks calculated from T1-weighted MR imaging data provide little information about residual fluid intelligence.Comment: 8 pages plus references, 3 figures, 2 tables. Submission to the ABCD Neurocognitive Prediction Challenge at MICCAI 201

Selective-logging and oil palm: Multitaxon impacts, biodiversity indicators, and trade-offs for conservation planning

Strong global demand for tropical timber and agricultural products has driven large-scale logging and subsequent conversion of tropical forests. Given that the majority of tropical landscapes have been or will likely be logged, the protection of biodiversity within tropical forests thus depends on whether species can persist in these economically exploited lands, and if species cannot persist, whether we can protect enough primary forest from logging and conversion. However, our knowledge of the impact of logging and conversion on biodiversity is limited to a few taxa, often sampled in different locations with complex land-use histories, hampering attempts to plan cost-effective conservation strategies and to draw conclusions across taxa. Spanning a land-use gradient of primary forest, once- and twice-logged forests, and oil palm plantations, we used traditional sampling and DNA metabarcoding to compile an extensive data set in Sabah, Malaysian Borneo for nine vertebrate and invertebrate taxa to quantify the biological impacts of logging and oil palm, develop cost-effective methods of protecting biodiversity, and examine whether there is congruence in response among taxa. Logged forests retained high species richness, including, on average, 70% of species found in primary forest. In contrast, conversion to oil palm dramatically reduces species richness, with significantly fewer primary-forest species than found on logged forest transects for seven taxa.Using a systematic conservation planning analysis, we show that efficient protection of primary-forest species is achieved with land portfolios that include a large proportion of logged-forest plots. Protecting logged forests is thus a cost-effective method of protecting an ecologically and taxonomically diverse range of species, particularly when conservation budgets are limited. Six indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies, and true bugs) proved to be consistently good predictors of the response of the other taxa to logging and oil palm. Our results confidently establish the high conservation value of logged forests and the low value of oil palm. Cross-taxon congruence in responses to disturbance also suggests that the practice of focusing on key indicator taxa yields important information of general biodiversity in studies of logging and oil palm