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991.
《Bioorganic & medicinal chemistry letters》2020,30(4):126882
Development of highly effective, safe, and fast-acting anti-depressants is urgently required for the treatment of major depressive disorder. It has been suggested that targeting 5-HT2A and 5-HT2C in addition to inhibition of serotonin reuptake may be beneficial in generating anti-depressant agents with better pharmacology and less adverse effects. We have developed phthalazinone-based compounds that potently bind to 5-HT2A, 5-HT2C, and the serotonin transporter. The representative compounds 11j and 11l displayed strong binding affinities against these targets, and showed favorable toxicity profiles as determined by hERG binding and CYP inhibition assays. Furthermore, these compounds presented promising anti-depressant effects comparable to fluoxetine and also synergistic effects with fluoxetine in forced swimming test, which implicates these compounds can be developed to help the treatment of major depressive disorder. 相似文献
992.
993.
自闭症谱系障碍(autism spectrum disorder,ASD)是一种精神致残的重要疾病,严重影响儿童身心健康,给家庭和社会带来沉重的负担。患者常出现不同程度胃肠道症状和伴有肠道微生物组成的改变,以此为切入点,近年越来越多的研究聚焦于ASD和肠道微生物的关系上。本文介绍了肠道微生物组成、肠―脑轴及ASD患者肠道微生物的主要变化,并从多个方面阐述了ASD与肠道微生物的关系。 相似文献
994.
Hirosi Matuo D. K. Rice D. M. Balthasar D. A. Cadenhead 《Chemistry and physics of lipids》1982,30(4):367-380
Mixed monolayers of two bipolar/bipolar systems have been studied and the results are compared with those obtained from similar monopolar/monopolar systems. DL-12-Hydroxyoctadecanoic acid, methyl DL-12-hydroxyoctadecanoate, and ethyl DL-12-hydroxyoctadecanoate were used as the bipolar substances in this paper. The surface pressure-area/molecule isotherms of both the DL-12-hydroxyoctadecanoic acid/methyl DL-12-hydroxyoctadecanoate system and the methyl DL-12-hydroxyoctadecanoate/ethyl DL-12-hydroxyoctadecanoate system were measured at a variety of compositions and temperatures. Taking advantage of the thermodynamic threatment which has been formulated by Motomura, the two-dimensional phase diagrams and the apparent molar entrophy, enthalpy and energy changes were evaluated for both systems. The DL-12-hydroxyoctadecanoic acid/ethyl DL-12-hydroxyoctadecanoate system exhibited a deformed cigar type diagram while the methyl DL-12-hydroxyoctadecanoate/ethyl DL-12-hydroxoctadecanoate system formed a normal cigar type diagram. The transition thermodynamic quantities of both the DL-12-hydroxyoctadecanoic acid/ethyl DL-12-hydroxoctadecanoate system and the methyl DL-12-hydroxyoctadecanoate/ethyl DL-12-hydroxyoctadecanoate system were respectively much larger than those of similar monopolar/monopolar systems: hexadecanoic acid/ethyl hexadecanoate and ethyl hexadecanoate/ethyl heptadecanoate. 相似文献
995.
Peter Tompa Monika Fuxreiter Christopher J. Oldfield Istvan Simon A. Keith Dunker Vladimir N. Uversky 《BioEssays : news and reviews in molecular, cellular and developmental biology》2009,31(3):328-335
Protein–protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein–protein recognition mechanism, mediated by disordered regions longer than 20–30 residues. Bioinformatics predictions and well‐characterized examples, such as the kinase‐inhibitory domain of Cdk inhibitors and the Wiskott–Aldrich syndrome protein (WASP)‐homology domain 2 of actin‐binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains. 相似文献
996.
Paul C. Archibald 《The Yale journal of biology and medicine》2021,94(3):383
Introduction: Work-related stress (WRS) and posttraumatic disorder (PTSD) is higher among Black adults relative to their White counterparts. Trauma exposure is not the only connection to increased risk for PTSD as WRS is highly associated with risk for PTSD. However, the factors that link WRS and PTSD among working Black adults is not well understood. Materials and Methods: Cross-sectional data from the National Survey of American Life was used to examine the relationship between WRS and PTSD among 2,139 working Black adults and to determine whether there are influencing factors. Results: Logistic regression analyses revealed that working Black adults who reported experiencing WRS was associated with higher odds of PTSD than those who reported no WRS (OR: 1.24, 95% CI: 1.04-1.48). The relationship was attenuated when depression, alcohol abuse, and major discrimination were added to the model (OR: 1.09, 95% CI: 0.87-1.36). Mediation analyses show that the average indirect effect of WRS on PTSD were 0.09 ± 0.04 for alcohol abuse, 0.14 ± 0.06 for depression, and 0.35 ± 0.10 for major discrimination. Conclusion: The results underscore the need for culturally responsive trauma-informed public health interventions for working Black adults. Public health practitioners should be alerted to the relationship between WRS and PTSD among working Black adults and the potential contributing factors (alcohol abuse, depression, and major discrimination). Special attention should be given to working Black females with their worse PTSD status and major discrimination experiences which demonstrated greater effect on the relationship between WRS and PTSD. 相似文献
997.
酵母过氧化物体生物合成缺陷突变株的诱变、筛选和鉴定 总被引:2,自引:0,他引:2
过氧化物体对生物的生长和发育非常重要,人类很多疾病就是由于过氧化物体生物合成缺陷引起。以解脂耶氏酵母E122为出发菌,采用硫酸二乙酯诱变,获得了两株过氧化物体生物合成缺陷突变株,其中一株为温度敏感的突变株。在正常生长条件下,突变株的免疫荧光分析显示弥散的染色模式,且在电镜下观察不到过氧化物体的形态结构。将克隆于表达载体pINA445上的目前所发现的与过氧化物体生物合成有关的基因转化这两株突变株,发现它们均不能恢复其在含油酸的培养基上的生长,表明这两个突变株是由与过氧化物体生物合成相关的新基因的突变引起。这两个突变株的获得为参与过氧化物体生物合成的新基因的发现奠定了基础。 相似文献
998.
alpha-Synuclein (alphaS) is an amyloidogenic neuronal protein associated with several neurodegenerative disorders. Although unstructured in solution, alphaS forms alpha-helices in the presence of negatively charged lipid surfaces. Moreover, alphaS was shown to interact with FAs in a manner that promotes protein aggregation. Here, we investigate whether alphaS has specific FA binding site(s) similar to fatty acid binding proteins (FABPs), such as the intracellular FABPs. Our NMR experiments reveal that FA addition results in i) the simultaneous loss of alphaS signal in both (1)H and (13)C spectra and ii) the appearance of a very broad FA (13)C-carboxyl signal. These data exclude high-affinity binding of FA molecules to specific alphaS sites, as in FABPs. One possible mode of binding was revealed by electron microscopy studies of oleic acid bilayers at pH 7.8; these high-molecular-weight FA aggregates possess a net negative surface charge because they contain FA anions, and they were easily disrupted to form smaller particles in the presence of alphaS, indicating a direct protein-lipid interaction. We conclude that alphaS is not likely to act as an intracellular FA carrier. Binding to negatively charged membranes, however, appears to be an intrinsic property of alphaS that is most likely related to its physiological role(s) in the cell. 相似文献
999.
Muhammad A. Usmani Zubair M. Ahmed Pamela Magini Victor Murcia Pienkowski Kristen J. Rasmussen Rebecca Hernan Faiza Rasheed Mureed Hussain Mohsin Shahzad Brendan C. Lanpher Zhiyv Niu Foong-Yen Lim Tommaso Pippucci Rafal Ploski Verena Kraus Karolina Matuszewska Flavia Palombo Jessica Kianmahd Saima Riazuddin 《American journal of human genetics》2021,108(7):1330-1341
1000.
E. Ba?ar B. Güntekin ?. Atagün B. Turp G?lba?? E. Tülay A. ?zerdem 《Cognitive neurodynamics》2012,6(1):11-20
Brain’s alpha activity and alpha responses belong to major electrical signals that are related to sensory/cognitive signal
processing. The present study aims to analyze the spontaneous alpha activity and visual evoked alpha response in drug free
euthymic bipolar patients. Eighteen DSM-IV euthymic bipolar patients (bipolar I n = 15, bipolar II n = 3) and 18 healthy controls were enrolled in the study. Patients needed to be euthymic at least for 4 weeks and psychotrop
free for at least 2 weeks. Spontaneous EEG (4 min eyes closed, 4 min eyes open) and evoked alpha response upon application
of simple visual stimuli were analyzed. EEG was recorded at 30 positions. The digital FFT-based power spectrum analysis was
performed for spontaneous eyes closed and eyes open conditions and the response power spectrum was also analyzed for simple
visual stimuli. In the analysis of spontaneous EEG, the ANOVA on alpha responses revealed significant results for groups (F(1,34) = 8.703; P < 0.007). Post-hoc comparisons showed that spontaneous EEG alpha power of healthy subjects was significantly higher than
the spontaneous EEG alpha power of euthymic patients. Furthermore, visual evoked alpha power of healthy subjects was significantly
higher than visual evoked alpha power of euthymic patients (F(1,34) = 4.981; P < 0.04). Decreased alpha activity in spontaneous EEG is an important pathological EEG finding in euthymic bipolar patients.
Together with an evident decrease in evoked alpha responses, the findings may lead to a new pathway in search of biological
correlates of cognitive impairment in bipolar disorder. 相似文献