1,721,135 research outputs found
Short-term maintenance on a high-sucrose diet alleviates aging-induced sleep fragmentation in drosophila
Full text linkSleep is a fundamental behavior in an animal’s life influenced by many internal and external factors, such as aging and diet. Critically, poor sleep quality places people at risk of serious medical conditions. Because aging impairs quality of sleep, measures to improve sleep quality for elderly people are needed. Given that diet can influence many aspects of sleep, we investigated whether a high-sucrose diet (HSD) affected aging-induced sleep fragmentation using the fruit fly, Drosophila melanogaster. Drosophila is a valuable model for studying sleep due to its genetic tractability and many similarities with mammalian sleep. Total sleep duration, sleep bout numbers (SBN), and average sleep bout length (ABL) were compared between young and old flies on a normal sucrose diet (NSD) or HSD. On the NSD, old flies slept slightly more and showed increased SBN and reduced ABL, indicating increased sleep fragmentation. Short-term maintenance of flies in HSD (up to 8 days), but not long-term maintenance (up to 35 days), suppressed aging-induced sleep fragmentation. Our study provides meaningful strategies for preventing the deterioration of sleep quality in the elderly
Metabolic control of daily locomotor activity mediated by tachykinin in Drosophila
Full text linkMetabolism influences locomotor behaviors, but the understanding of neural curcuit control for that is limited. Under standard light-dark cycles, Drosophila exhibits bimodal morning (M) and evening (E) locomotor activities that are controlled by clock neurons. Here, we showed that a high-nutrient diet progressively extended M activity but not E activity. Drosophila tachykinin (DTk) and Tachykinin-like receptor at 86C (TkR86C)-mediated signaling was required for the extension of M activity. DTk neurons were anatomically and functionally connected to the posterior dorsal neuron 1s (DN1ps) in the clock neuronal network. The activation of DTk neurons reduced intracellular Ca2+ levels in DN1ps suggesting an inhibitory connection. The contacts between DN1ps and DTk neurons increased gradually over time in flies fed a high-sucrose diet, consistent with the locomotor behavior. DN1ps have been implicated in integrating environmental sensory inputs (e.g., light and temperature) to control daily locomotor behavior. This study revealed that DN1ps also coordinated nutrient information through DTk signaling to shape daily locomotor behavior
The Change in Circadian Rhythms in P301S Transgenic Mice is Linked to Variability in Hsp70-related Tau Disaggregation
Full text linkCircadian disruption often involves a neurodegenerative disorder, such as Alzheimer's disease or frontotemporal dementia, which are characterized by intraneuronal tau accumulations. The altered sleep pattern and diurnal rhythms in these disorders are the results of tau pathology. The circadian disturbance in reverse is thought to develop and potentially aggravate the condition. However, the underlying mechanism is not fully understood. In this study, perturbed oscillations in BMAL1 , the core clock gene, were observed in P301S tau transgenic mice. Tau fractionation analysis of the hippocampus revealed profound fluctuations in soluble and insoluble tau protein levels that were in opposite directions to each other according to zeitgeber time. Interestingly, a diurnal oscillation was detected in the heat shock 70 kDa protein 1A (Hsp70) chaperone that was in-phase with soluble tau but out-of-phase with insoluble tau. Tau protein levels decreased in the soluble and insoluble fractions when Hsp70 was overexpressed in HEK293T cells. Transfection of the BMAL1 carrying vector was continual with the increase in Hsp70 expression and diminished tau protein levels, and it was effectively attenuated by the knockdown of Hsp70, suggesting that Bmal1 could modulate tau protein by Hsp70. Our results suggest that altered circadian oscillations affect tau status and solubility by modulating Hsp70 expression in an experimental model of tau pathology. These findings suggest Hsp70 as a possible pathogenic link between circadian disruption and aggravations of tau pathology
Systematic modeling-driven experiments identify distinct molecular clockworks underlying hierarchically organized pacemaker neurons
Full text linkIn metazoan organisms, circadian ( approximately 24 h) rhythms are regulated by pacemaker neurons organized in a master-slave hierarchy. Although it is widely accepted that master pacemakers and slave oscillators generate rhythms via an identical negative feedback loop of transcription factor CLOCK (CLK) and repressor PERIOD (PER), their different roles imply heterogeneity in their molecular clockworks. Indeed, in Drosophila, defective binding between CLK and PER disrupts molecular rhythms in the master pacemakers, small ventral lateral neurons (sLN(v)s), but not in the slave oscillator, posterior dorsal neuron 1s (DN1(p)s). Here, we develop a systematic and expandable approach that unbiasedly searches the source of the heterogeneity in molecular clockworks from time-series data. In combination with in vivo experiments, we find that sLN(v)s exhibit higher synthesis and turnover of PER and lower CLK levels than DN1(p)s. Importantly, light shift analysis reveals that due to such a distinct molecular clockwork, sLN(v)s can obtain paradoxical characteristics as the master pacemaker, generating strong rhythms that are also flexibly adjustable to environmental changes. Our results identify the different characteristics of molecular clockworks of pacemaker neurons that underlie hierarchical multi-oscillator structure to ensure the rhythmic fitness of the organism
Abnormality Detection in Wireless Capsule Endoscopy with Unsupervised Feature Extraction
No full textMASS-TRANSPORT STUDY OF NAFION(R) COATINGS SATURATED WITH [OS(BPY)(3)](2+) BY AN ELECTROCHEMICAL QUARTZ-CRYSTAL MICROBALANCE
No full textIon transport out of and into the Nafion(R) coating on an electrode during the electrochemical processes was studied using an electrochemical quartz crystal microbalance (EQCM). After saturated loading of [Os(bpy)(3)](2+), the first cyclic voltammogram (CV) initiated from the lower limit showed an anodic peak around 0.85 V vs. Ag\AgCl which, according to a previous study by Anson's group, corresponds to ejection of the [Os(bpy)(3)](3+) complex from the Nafion(R) coating. However, the frequency change-potential (Delta f-E) curve obtained by EQCM showed an increase in the mass on the first positive scan. These contradictory results can be explained by the movement of water molecules in a direction opposite to that of [Os(bpy)(3)](3+) complexes. After a number of successive cycles, a steady state voltammogram was obtained. In this case the mass change was attributed mainly to the movement of the hydrated electroinactive counter-cations of the supporting electrolyte. The hydration numbers for two of the supporting electrolyte cations are in good agreement with the published results.We would like to acknowledge enlightening discussions with Professor Fred C. Anson and Dr. Minglian Shi. We thank Dr. Chanseung Park for the help with the impedance measurements. This work was supported by the Non-Directed Research Fund, Korea Research Foundation, 1993
Drosophila peptidyl-prolyl cis/trans isomerase-like 4 regulates circadian rhythm by supporting high-amplitude oscillations of PERIOD
No full textPeptidyl-prolyl cis/trans isomerases (PPIases) accelerate proline peptide bond isomerization, affecting substrate protein function. In this study, through RNAi-based behavioral screening of PPIases in Drosophila melanogaster, we identified CG5808, termed Drosophila peptidyl-prolyl cis/trans isomerase-like 4 (dPPIL4), as crucial for circadian rhythm regulation. Knockdown of dppil4 in clock cells lengthened the circadian rhythm period and decreased rhythmicity, accompanied by a significant reduction of core clock protein PERIOD (PER). d ppil4 knockdown downregulated per transcription and reduced phosphorylation at Ser5 in the RNA polymerase II C-terminal domain, critical for transcription elongation. In addition, dPPIL4 stabilized Cullin1 of the Skp1-Cullin1-F-box protein complex, a key regulator of PER degradation. Our findings suggest that dPPIL4 supports high-amplitude PER oscillation by enhancing both synthesis and degradation processes in a timely manner. In conclusion, our study underscores the importance of high-amplitude PER oscillations in PER for robust circadian rhythms and highlights the critical role of dPPIL4 in this process
Drosophila ubiquitin-specific peptidase 14 stabilizes the PERIOD protein by regulating a ubiquitin ligase SLIMB
No full textThe circadian clock orchestrates behavior and physiology through the oscillation of key clock proteins like PERIOD (PER). Here, we investigate the role of ubiquitin-specific peptidase 14 (USP14) in modulating PER stability and circadian rhythms in Drosophila. We find that overexpression of USP14 in clock cells reduces PER protein levels without altering its mRNA levels whereas USP14 knockdown increases PER protein levels, suggesting that USP14 regulates PER post-translationally. Interestingly, despite these alterations in PER levels, neither USP14 overexpression nor knockdown significantly impacts circadian behavioral rhythms, likely because of slight effects on PER levels in small ventral lateral neurons (sLN(v)s). Further analysis shows that USP14 physically interacts with Supernumerary Limbs (SLIMB), a protein involved in PER degradation. Moreover, reducing slimb expression mitigates the effects of USP14 on PER protein stability. Mass spectrometry identifies two ubiquitination sites on PER (Lys1117 and Lys1118) critical for its degradation. Expression of PER(1117A, 1118A) mutant in per(01) background impairs circadian rhythm strength. In conclusion, this study demonstrates that Drosophila USP14 indirectly modulates PER protein stability by affecting SLIMB and highlights the critical role of specific ubiquitination sites on PER in maintaining circadian rhythms
Implementing an artificial synapse and neuron using a Si nanowire ion-sensitive field-effect transistor and indium-gallium-zinc-oxide memristors
No full textIn this study, we implement an artificial synapse and neuron in a single platform by combining a silicon nanowire (SiNW) ion-sensitive field-effect transistor (ISFET), an indium-gallium-zinc-oxide (IGZO) memristor, and a voltage-controlled oscillator (VCO). The chemical and electrical operations of the synapse are emulated using the pH sensor operation of the ISFET and long-term potentiation/short-term plasticity of the IGZO memristor, respectively. The concentration of hydrogen ions in an electrolyte is successfully transformed via a VCO-based neuron into modulation of synaptic strength, i.e., the current of the memristor. It mimics the strength of the synaptic connection modulated by the concentration of the neurotransmitter. Thus, the chemical-electrical signal conversion in chemical synapses is clearly demonstrated. Furthermore, the proposed artificial platform can discriminate the chemical synapse from the electrical synapse and the path of the neuro-signal propagation and that of memorization/update of synaptic strength. This can potentially provide a new insight into the principles of brain-inspired computing that can overcome the bottleneck of the state-of-the-art von-Neumann computing systems
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