Prohormone convertase 2 (PC2) is essential for the biosynthesis of many neuropeptides, including several of them in hippocampus. In mouse brain, lacking an enzymatically active PC2 (PC2-null) causes accumulation of many neuropeptides in their precursor or intermediate forms. Little is known about how a PC2-null state may affect the function of the hippocampus. In this study, adult PC2-null mice and their wildtype (WT) littermates were subjected to three analyses to determine possible changes associated with PC2-null at physiological, behavioral, and molecular levels, respectively, under normal and stressed conditions. Electrophysiological recordings of hippocampal slices were performed to measure evoked field-excitatory postsynaptic potentials (EPSP), long-term potentiation (LTP), and paired-pulse facilitation (PPF). Morris water maze (MWM) testing was conducted to examine behavioral changes that are indicative of hippocampal integrity. Quantitative mass spectrometry analysis was used to determine changes in resses originating in other regions of the brain. © 2020 Wiley Periodicals, Inc.Overexpression of either miR-302 or miR-302/367 cluster induces reprogramming of cancer cells and exerts tumor-suppressive effects by induction of mesenchymal-to-epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR-16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR-16 in MDA-MB-231 and SK-BR-3 breast cancer cells following overexpression of miR-302/367 cluster and investigated whether transfection of these cells by a mature miR-16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR-16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR-16 counteracted both the reprogramming effect and the antitumor function of miR-302/367 in the breast cancer cells. Current results indicate that miR-16 can work as an adjuvant to improve both cancer cell reprogramming and tumor-suppressive function of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer. © 2020 International Union of Biochemistry and Molecular Biology.For nearly 50 years immunogold labeling on ultrathin sections has been successfully used for protein localization in laboratories worldwide. In theory and in practice, this method has undergone continual improvement over time. In this study, we carefully analyzed circulating protocols for postembedding labeling to find out if they are still valid under modern laboratory conditions, and in addition, we tested unconventional protocols. For this, we investigated immunolabeling of Epon-embedded cells, immunolabeling of cells treated with osmium, and the binding behavior of differently sized gold particles. Here we show that (in contrast to widespread belief) immunolabeling of Epon-embedded cells and of cells treated with osmium tetroxide is actually working. Furthermore, we established a "speed protocol" for immunolabeling by reducing antibody incubation times. Finally, we present our results on three-dimensional immunogold labeling. © 2020 The Authors. Microscopy Research and Technique Published by Wiley Periodicals, Inc.Behavioral data shows that humans and animals have the capacity to learn rules of associations applied to specific examples, and generalize these rules to a broad variety of contexts. https://www.selleckchem.com/products/direct-red-80.html This article focuses on neural circuit mechanisms to perform a context-dependent association task that requires linking sensory stimuli to behavioral responses and generalizing to multiple other symmetrical contexts. The model uses neural gating units that regulate the pattern of physiological connectivity within the circuit. These neural gating units can be used in a learning framework that performs low-rank matrix factorization analogous to recommender systems, allowing generalization with high accuracy to a wide range of additional symmetrical contexts. The neural gating units are trained with a biologically inspired framework involving traces of Hebbian modification that are updated based on the correct behavioral output of the network. This modeling demonstrates potential neural mechanisms for learning context-dependent association rules and for the change in selectivity of neurophysiological responses in the hippocampus. The proposed computational model is evaluated using simulations of the learning process and the application of the model to new stimuli. Further, human subject behavioral experiments were performed and the results validate the key observation of a low-rank synaptic matrix structure linking stimuli to responses. © 2020 Wiley Periodicals, Inc.The effect of caffeine on sleep has been well documented. However, most studies examined this relationship in laboratories or used a cross-sectional design analysing between-person differences. This study investigated the within-person relationship between caffeine intake and sleep duration at home. In a national database, 377 participants (aged 35-85 years) completed a 7-day diary study. Sleep duration was measured by Actigraphy and caffeine intake was self-reported in sleep logs. Three analytic strategies were used. The average sleep duration and the average caffeine intake were not significantly correlated. Multilevel regressions using daytime caffeine intake to predict night-time sleep, and using night-time sleep to predict next day caffeine intake, also did not detect any significant effect. Then dynamical systems analysis was performed, where the daily change rate and change tendency of caffeine and sleep were estimated, and the relationship among these momentums was examined. Results revealed a significant effect of sleep duration on the change tendency of caffeine use a shorter sleep duration predicted a stronger tendency to consume caffeine, and this phenomenon was only found in middle-aged adults (aged 35-55 years) not in older adults (aged 55+). This study did not detect any effect of daily caffeine intake on sleep duration, implying that habitual use of caffeine in real life may not coincide with laboratory findings, and that using caffeine to compensate for sleep loss is the habit of middle-aged adults, not the elderly. The advantage of using a dynamic approach to analyse interrelated processes with uncertain time lags is also highlighted. © 2020 European Sleep Research Society.