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1.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
2.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
3.
4.
McIntyre Christa K.; Marriott Lisa K.; Gold Paul E. 《Canadian Metallurgical Quarterly》2003,117(2):320
The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
We could not imagine a more appropriate inauguration of the Psychology of Aesthetics, Creativity, and the Arts (PACA) going to four issues per year than with a special issue honoring the life and work of the great aesthetician and psychologist, Rudolf Arnheim. PACA is off to a great start. With this move to four issues per year, we are restarting our numbering system, so this special issue is Volume 1, Issue 1. As you read the articles in this issue, we hope that you enjoy reflecting on how much Rudolf Arnheim has contributed to the field of psychology of aesthetics. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
6.
Luginbuhl P. Collins S.D. Racine G.-A. Gretillat M.-A. De Rooij N.F. Brooks K.G. Setter N. 《Journal of microelectromechanical systems》1997,6(4):337-346
The fabrication using silicon micromachining and characterization of an acoustic Lamb wave actuator is presented. The intended use of the device is for mass transport and sensor applications. The device consists of dual interdigitated transducers patterned on a thin-film composite membrane of silicon nitride, platinum, and a sol-gel-derived piezoelectric ceramic (PZT) thin film. The acoustic properties of the device are presented along with preliminary applications to mechanical transport and liquid delivery systems. Improved acoustic signals and improved mass transport are achieved with PZT over present Lamb wave devices utilizing ZnO or AlN as the piezoelectric transducer 相似文献
7.
Converging inputs to the entorhinal cortex from the piriform cortex and medial septum: facilitation and current source density analysis. J. Neurophysiol. 78: 2602-2615, 1997. The entorhinal cortex receives sensory inputs from the piriform cortex and modulatory inputs from the medial septum. To examine short-term synaptic facilitation effects in these pathways, current source density (CSD) analysis was used first to localize the entorhinal cortex membrane currents, which generate field potentials evoked by stimulation of these afferents. Field potentials were recorded at 50-micron intervals through the medial entorhinal cortex in urethan-anesthetized rats and the one-dimensional CSD was calculated. Piriform cortex stimulation evoked a surface-negative, deep-positive field potential component in the entorhinal cortex with mean onset and peak latencies of 10.4 and 18.4 ms. The component followed brief 100-Hz stimulation, consistent with a monosynaptic response. CSD analysis linked the component to a current sink, which often began in layer I before peaking in layer II. A later, surface-positive field potential component peaked at latencies near 45 ms and was associated with a current source in layer II. Medial septal stimulation evoked positive and negative field potential components which peaked at latencies near 7 and 16 ms, respectively. A weaker and more prolonged surface-negative, deep-positive component peaked at latencies near 25 ms. The early components were generated by currents in the hippocampal formation, and the late surface-negative component was generated by currents in layers II to IV of the entorhinal cortex. Short-term facilitation effects in conscious animals were examined using electrodes chronically implanted near layer II of the entorhinal cortex. Paired-pulse stimulation of the piriform cortex at interpulse intervals of 30 and 40 ms caused the largest facilitation (248%) of responses evoked by the second pulse. Responses evoked by medial septal stimulation also were facilitated maximally (59%) by a piriform cortex conditioning pulse delivered 30-40 ms earlier. Paired pulse stimulation of the medial septum caused the largest facilitation (149%) at intervals of 70 ms, but piriform cortex evoked responses were facilitated maximally (46%) by a septal conditioning pulse 100-200 ms earlier. Frequency potentiation effects were maximal during 12- to 18-Hz stimulation of either the piriform cortex or medial septum. Occlusion tests suggested that piriform cortex and medial septal efferents activate the same neurons. The CSD analysis results show that evoked field potential methods can be used effectively in chronically prepared animals to examine synaptic responses in the converging inputs from the piriform cortex and medial septum to the entorhinal cortex. The short-term potentiation phenomena observed here suggest that low-frequency activity in these pathways during endogenous oscillatory states may enhance entorhinal cortex responsivity to olfactory inputs. 相似文献
8.
MH Boyle DR Offord D Campbell G Catlin P Goering E Lin YA Racine 《Canadian Metallurgical Quarterly》1996,41(9):549-558
OBJECTIVE: To describe the methodology of a province-wide, cross-sectional, epidemiologic study of psychiatric disorder among those aged 15 years and over living in household dwellings in Ontario. METHOD: Respondents for the survey were drawn from households (N = 13002) participating in a province-wide health survey. One person per household was selected, and 9953 (76.5%) participated. RESULTS: Participants and nonparticipants were similar to each other. An extensive array of data, including measures of psychiatric disorder classified using a revised version of the Composite International Diagnostic Interview (CIDI), are available for all respondents. CONCLUSIONS: The Ontario Health Supplement is contained in a public-use data file at the Ontario Ministry of Health and is available to investigators for study. A strong survey design, careful measurement, and acceptable levels of response provide the rationale for our inviting researchers to access and use the Ontario Health Supplement data base. 相似文献
9.
In a conceptual replication of A. Biglan et al (see record 1989-39898-001), 288 Ss rated their emotional and behavioral responses to aggressive, distressed, and neutral behaviors. The stimulus behaviors occurred in the context of casual relationships and were portrayed by male and female actors. Consistent with Biglan et al, it was found that aggressive behaviors evoked angry emotions and negative behavioral responses; distressed behaviors evoked both angry and concerned emotions and supportive behavioral responses. However, in contrast to the original results, evidence was also found of negative (primarily avoidant) behavioral responses to distressed behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
10.
This study evaluates the impact assessment methodologies used by Uganda's Water Hyacinth Control Programme in Lake Victoria, a domestic project with transboundary implications. The Control Programme sought to reduce infestations of water hyacinth (Eichhornia crassipes), an aquatic weed native to South America, through the use of integrated chemical, mechanical and biological methods. The environmental impact assessment for the project was conducted by Aquatics Unlimited, with support from the United States Agency for International Development. Although the case study involves a domestic impact assessment, it raised transboundary concerns. One of the major outcomes of the assessment was recognition of the need for informed involvement of the other riparian countries, Kenya and Tanzania, in the assessment process to ensure a regional effort among all three East African Community Partner States to control water hyacinth and other invasive weeds in Lake Victoria. 相似文献