Drosophila CrebB is a Substrate of the Nonsense-Mediated mRNA Decay Pathway that Sustains Circadian Behaviors

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on geni-talia 5 (Smg5) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila

The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology

Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKa, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively deterrnine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities

AVQS: Attack Route-Based Vulnerability Quantification Scheme for Smart Grid

A smart grid is a large, consolidated electrical grid system that includes heterogeneous networks and systems. Based on the data, a smart grid system has a potential security threat in its network connectivity. To solve this problem, we develop and apply a novel scheme to measure the vulnerability in a smart grid domain. Vulnerability quantification can be the first step in security analysis because it can help prioritize the security problems. However, existing vulnerability quantification schemes are not suitable for smart grid because they do not consider network vulnerabilities. We propose a novel attack route-based vulnerability quantification scheme using a network vulnerability score and an end-to-end security score, depending on the specific smart grid network environment to calculate the vulnerability score for a particular attack route. To evaluate the proposed approach, we derive several attack scenarios from the advanced metering infrastructure domain. The experimental results of the proposed approach and the existing common vulnerability scoring system clearly show that we need to consider network connectivity for more optimized vulnerability quantification

Metabolic flux from the Krebs cycle to glutamate transmission tunes a neural brake on seizure onset

Kohlschutter-Tonz syndrome (KTS) manifests as neurological dysfunctions, including early-onset seizures. Mutations in the citrate transporter SLC13A5 are associated with KTS, yet their underlying mechanisms remain elusive. Here, we report that a Drosophila SLC13A5 homolog, I'm not dead yet (Indy), constitutes a neurometabolic pathway that suppresses seizure. Loss of Indy function in glutamatergic neurons caused "bang-induced" seizure-like behaviors. In fact, glutamate biosynthesis from the citric acid cycle was limiting in Indy mutants for seizure-suppressing glutamate transmission. Oral administration of the rate-limiting alpha-ketoglutarate in the metabolic pathway rescued low glutamate levels in Indy mutants and ameliorated their seizure-like behaviors. This metabolic control of the seizure susceptibility was mapped to a pair of glutamatergic neurons, reversible by optogenetic controls of their activity, and further relayed onto fan-shaped body neurons via the ionotropic glutamate receptors. Accordingly, our findings reveal a micro-circuit that links neural metabolism to seizure, providing important clues to KTS-associated neurodevelopmental deficits. Author summary Kohlschutter-Tonz syndrome (KTS) is a neurodevelopmental disorder linked to two distinct genomic loci encoding the citrate transporter SLC13A5 and synaptic protein ROGDI, respectively. An early-onset seizure is the most prominent neurological symptom in KTS patients, yet how these genes contribute to the control of seizure susceptibility remains poorly understood. Our study establishes behavioral models of seizure in Drosophila mutants of KTS-associated genes and demonstrates a genetic, metabolic, and neural pathway of seizure suppression. We discover that the metabolic flux of the Krebs cycle to glutamate biosynthesis plays a critical role in scaling seizure-relevant glutamate transmission. We further map this seizure-suppressing pathway to a surprisingly small number of glutamatergic neurons and their ionotropic glutamate transmission onto a key sleep-promoting locus in the adult fly brain. Given that the excitatory amino acid glutamate is considered a general seizure-promoting neurotransmitter, our findings illustrate how glutamatergic transmission can have opposing effects on seizure susceptibility in the context of a micro-neural circuit, possibly explaining drug-resistant epilepsy. This seizure-suppressing locus in the Drosophila brain is also implicated in metabolism, circadian rhythms, and sleep, revealing the conserved neural principles of their intimate interaction with epilepsy across species

Memory-in-pixel circuit with low temperature poly-Si and oxide TFTs

Memory-in-pixel (MIP) circuit has been studied for years to reduce power consumption of display products. Displays with MIP circuit can reduce power consumption because of their much lower frame rate than that of conventional displays using memory characteristics. Meanwhile, commercial display products have begun to introduce display circuits using low temperature poly-silicon and oxide (LTPO) TFTs to improve the performance and to use an advantage of extremely low leakage current of oxide TFTs. In this paper, we propose a new MIP circuit to achieve low power consumption as well as high reliability using LTPO TFTs

Detection of Broken Outer-Cage Bars for Double-Cage Induction Motors Under the Startup Transient

(c) 2009 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Unlike single-cage rotor fault detection, fast Fourier transform (FFT)-based steady-state spectrum analysis techniques can fail to detect outer-cage faults in double-cage induction motors due to the small outer-cage current under running conditions. Double-cage motors are typically employed in applications that require loaded starts. This makes the outer cage vulnerable to fatigue failure since it must withstand the high starting current and long startup time frequently. However, there are only a few publications that investigate detection techniques specifically for double-cage motors. In this paper, considering that the influence of the faulty outer cage is strong at startup due to the large outer-cage current, detection of outer-cage faults under the startup transient is investigated. A discrete-wavelet-transform-based method is proposed as a viable solution to the detection of outer-cage faults for double-cage motors. An experimental study on fabricated copper double-cage induction motors shows that the proposed method provides sensitive and reliable detection of double-cage rotor faults compared to FFT.This work was supported in part by the Spanish “Ministerio de Educación y Ciencia,” in the framework of the “Programa Nacional de Proyectos de Investigación Fundamental,” under Project Reference DPI2008-06583/DPI, and in part by the Human Resources Development of Korea Institute of Energy Technology Evaluation and Planning under Grant 20114010203010 funded by the Korean Government Ministry of Knowledge EconomyAntonino-Daviu, J.; Riera-Guasp, M.; Pons Llinares, J.; Park, J.; Lee, SB.; Yoo, J.; Kral, C. (2012). Detection of Broken Outer-Cage Bars for Double-Cage Induction Motors Under the Startup Transient. IEEE Transactions on Industry Applications. 48(5):1539-1548. https://doi.org/10.1109/TIA.2012.2210173S1539154848

A sleep-like state in Hydra unravels conserved sleep mechanisms during the evolutionary development of the central nervous system

Sleep behaviors are observed even in nematodes and arthropods, yet little is known about how sleep-regulatory mechanisms have emerged during evolution. Here, we report a sleep-like state in the cnidarian Hydra vulgaris with a primitive nervous organization. Hydra sleep was shaped by homeostasis and necessary for cell proliferation, but it lacked free-running circadian rhythms. Instead, we detected 4-hour rhythms that might be generated by ultradian oscillators underlying Hydra sleep. Microarray analysis in sleep-deprived Hydra revealed sleep-dependent expression of 212 genes, including cGMP-dependent protein kinase 1 (PRKG1) and ornithine aminotransferase. Sleep-promoting effects of melatonin, GABA, and PRKG1 were conserved in Hydra. However, arousing dopamine unexpectedly induced Hydra sleep. Opposing effects of ornithine metabolism on sleep were also evident between Hydra and Drosophila, suggesting the evolutionary switch of their sleep-regulatory functions. Thus, sleep-relevant physiology and sleep-regulatory components may have already been acquired at molecular levels in a brain-less metazoan phylum and reprogrammed accordingly

INVESTIGATING WATER QUALITY WITH RESPECT TO ALTITUDE OF LAKES AROUND THE NORTHERN ROCKLAND COUNTY IN NEW YORK

Water is essential to the survival of all living organisms, and protecting this valuable resource is vitally important. Water quality is a measure of the conditions of water relative to the requirements of one or more biotic species. Knowing water’s physical, chemical and biological characteristics allow experts to determine whether it is suitable for aquatic life or human consumption. This study attempted to examine the relations of water quality parameters with lake altitudes. Ten lakes were chosen to evaluate their water quality with essential parameters such as ORP, total hardness, pH change, total alkalinity change, dissolved carbonate concentration and dissolved copper concentration. The ten lakes were located within 30 miles diameter, and altitudes were well distributed. Our conclusion suggests that the heavy metals and compounds such as lead, fluoride, iron, mercury, nitrate, nitrite, chromium, bromine, chlorine and sulfate were undetectable with the kits used in this research. The change of ORP, total hardness, pH, total alkalinity and dissolved copper concentration had weak correlation on linear regression analysis (R2 <0.4352), while the change of carbonate concentration was highly correlated with the increase of altitude (R2 0.8814). There could exist a subtle relationship among parameters other than those of water quality, such as the resident population near the water sources