235 research outputs found

    Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

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    This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.We thank Daniel Abebe for mouse colony maintenance and Kurt Auville for additional assistance with confocal imaging. We thank UNC Vector Core and Ed Boyden, MIT, Cambridge, MA, USA for generously providing AAV9-syn-Chrimson-TdTomato and AAV9-syn-Chronos-GFP. This work was supported by an intramural award to C.J.M. from the Eunice Kennedy–Shriver National Institute of Child Health and Human Development and a Competitive Fellowship Award to J.C.W. from the National Institute of Neurological Disorders and Strok

    mRNA decay analysis in Drosophila melanogaster: Drug-induced changes in glutathione S-transferase D21 mRNA stability

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    We have established an in vivo system to investigate mechanisms by which pentobarbital (PB), a psychoactive drug with a sedative effect, changes the rate of decay of gstD21 mRNA (encoding a Drosophila glutathione S-transferase). Here we describe methods for the use of hsp70 promoter-based transgenes and transgenic lines to determine mRNA half-lives by RNase protection assays in Drosophila. We are able to identify and map putative decay intermediates by cRT-PCR and DNA sequencing of the resulting clones. Our results indicate that the 3′-UTR of gstD21 mRNA is responsive to PB by regulating mRNA decay and that the cis-acting element(s) responsible for the PB-mediated stabilization resides in a 59 nucleotide sequence in the 3′-UTR of the gstD21 mRNA (Akgül and Tu, 2007).National Institute of Environmental Health Sciences (NIEHS) (ES02678

    2D-Based 3D Volume Retrieval Using Singular Value Decomposition of Detected Regions

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    In this paper, a novel 3D retrieval model to retrieve medical volumes using 2D images as input is proposed. The main idea consists of applying a multi–scale detection of saliency of image regions. Then, the 3D volumes with the regions for each of the scales are associated with a set of projections onto the three canonical planes. The 3D shape is indirectly represented by a 2D–shape descriptor so that the 3D–shape matching is transformed into measuring similarity between 2D–shapes. The shape descriptor is defined by the set of the k largest singular values of the 2D images and Euclidean distance between the vector descriptors is used as a similarity measure. The preliminary results obtained on a simple database show promising performance with a mean average precision (MAP) of 0.82 and could allow using the approach as part of a retrieval system in clinical routine

    Unlocking the secrets of Al-tobermorite in Roman seawater concrete

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    Ancient Roman syntheses of Al-tobermorite in a 2000-year-old concrete block submerged in the Bay of Pozzuoli (Baianus Sinus), near Naples, have unique aluminum-rich and silica-poor compositions relative to hydrothermal geological occurrences. In relict lime clasts, the crystals have calcium contents that are similar to ideal tobermorite, 33 to 35 wt%, but the low-silica contents, 39 to 40 wt%, reflect Al3+ substitution for Si4+ in Q(2)(1Al), Q(3)(1Al), and Q(3)(2Al) tetrahedral chain and branching sites. The Al-tobermorite has a double silicate chain structure with long chain lengths in the b [020] crystallographic direction, and wide interlayer spacing, 11.49 angstrom. Na+ and K+ partially balance Al3+ substitution for Si4+. Poorly crystalline calcium-aluminum-silicate-hydrate (C-A-S-H) cementitious binder in the dissolved perimeter of relict lime clasts has Ca/(Si+Al) = 0.79, nearly identical to the Al-tobermorite, but nanoscale heterogeneities with aluminum in both tetrahedral and octahedral coordination. The concrete is about 45 vol% glassy zeolitic tuff and 55 vol% hydrated lime-volcanic ash mortar; lime formed <10 wt% of the mix. Trace element studies confirm that the pyroclastic rock comes from Flegrean Fields volcanic district, as described in ancient Roman texts. An adiabatic thermal model of the 10 m(2) by 5.7 m thick Baianus Sinus breakwater from heat evolved through hydration of lime and formation of C-A-S-H suggests maximum temperatures of 85 to 97 degrees C. Cooling to seawater temperatures occurred in two years. These elevated temperatures and the mineralizing effects of seawater and alkali- and alumina-rich volcanic ash appear to be critical to Al-tobermorite crystallization. The long-term stability of the Al-tobermorite provides a valuable context to improve future syntheses in innovative concretes with advanced properties using volcanic pozzolans

    Comparative Study of RP-HPLC and UV Spectrophotometric Techniques for the Simultaneous Determination of Amoxicillin and Cloxacillin in Capsules

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    Reversed-phase HPLC and UV spectrophotometric techniques using water as solvent have been developed and validated for the simultaneous determination of amoxicillin and cloxacillin in capsules. For both techniques, the linearity range of 60.073x2013;140.0 µg/mL was studied. The spectrophotometric data show that non-derivative techniques, such as absorbance ratio and compensation, and ratio spectra first-order derivative could be successfully used for the co-assay of amoxicillin and cloxacillin. Based on the statistical comparison of spectrophotometric and chromatographic data, the interchangeability between HPLC and UV spectrophotometric techniques has been suggested for the routine analysis

    Garlic Accelerates Red Blood Cell Turnover and Splenic Erythropoietic Gene Expression in Mice: Evidence for Erythropoietin-Independent Erythropoiesis

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    Garlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects

    Viral infections in prostate carcinomas in Chilean patients

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    © 2015 Rodríguez et al.Background: A few viruses have been detected in prostate cancer, however their role in the development of this malignancy has not been determined. The aim of this study was to analyze the presence and functionality of human papillomavirus (HPV) and polyomaviruses (BKPyV and JCPyV) in prostate carcinomas in Chilean patients. Methods: Sixty-nine primary prostate carcinomas were analyzed for the presence of HPV, BKPyV and JCPyV using standard polymerase chain reaction protocols. In addition, when samples were positive for HPyV, large T antigen (TAg) transcripts were analyzed using reverse transcriptase PCR. Results: HPV and JCPyV were not detected in any specimens (0/69, 0 %); whereas, BKPyV was detected in 6/69 PCas (8.7 %). We did not find a statistically significant association between the presence of BKPyV and age (p∈=∈0.198) or Gleason score (p∈=∈0.268). In addition, 2/6 (33 %) BKPyV positive specimens showed detectable levels of TAg transcripts. Conclusions:

    Prediction model for phenology of grapevine cultivars with hot water treatment

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    O objetivo deste trabalho foi elaborar um modelo de previsão da fenologia de cultivares de videira (Bordô, Cabernet Sauvignon, Moscato Embrapa, Paulsen 1103, SO4 e IAC 572) com uso de tratamento de água quente. O tratamento térmico com água quente consistiu de combinações de três temperaturas (50, 53 e 55°C) com três intervalos de tempo (30, 45 e 60 min), com ou sem hidratação prévia por 30 min. Após os tratamentos, as estacas foram plantadas a campo e seu desenvolvimento fenológico foi avaliado por dois meses. As seis cultivares estudadas apresentaram respostas distintas quanto à influência dos fatores temperatura e tempo, mas não diferiram significativamente quanto à hidratação. Foi possível desenvolver um modelo matemático para uso do tratamento de água quente em estacas de videira, baseado no desenvolvimento fenológico (yfenologia= 48,268 - 0,811x1 - 0,058x2) e validado com as variáveis brotação e emissão de raízes. Recomenda-se, a partir do modelo desenvolvido, que o tratamento de água quente seja aplicado na faixa de temperatura entre 48 e 51°C para estacas de todas as cultivares.The objective of this work was to prepare a prediction model for the phenology of grapevine cultivars (Bordô, Cabernet Sauvignon, Moscato Embrapa, Paulsen 1103, SO4, and IAC 572) using hot water treatment. The heat treatment with hot water consisted of ombinations of three temperatures (50, 53, and 55°C) and three time periods (30, 45, and 60 min), with or without previous hydration for 30 min. After the treatments, the cuttings were planted in the field and their phenological development was evaluated during two months. The six studied cultivars presented different responses to the effects of the factors temperature and time, but did not differ significantly regarding hydration. It was possible to develop a mathematical model for the use of hot water treatment in grapevine cuttings, based on phenological development (yphenology = 48.268 - 0.811x1 - 0.058x2) and validated by the variables sprouting and root emission. From the developed model, it is recommended that the hot water treatment be applied in the temperature range between 48 and 51°C for cuttings of all cultivars
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