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The wave-induced local fluid flow mechanism is relevant to the complex heterogeneity of pore structures in rocks. The analysis of the local fluid flow mechanism is useful for accurately describing the wave propagation characteristics in reservoir rocks. In the exploration and production of hydrocarbon reservoirs, the real stratum may be partially saturated with a multi-phase fluid mixture in general. Therefore, it is of great significance to investigate the wave velocity dispersion and attenuation features in relation to pore structures and fluids. In this work, the characteristics of fabric microstructures are obtained on the basis of pressure dependency of dry rock moduli using the effective medium theory. A novel anelasticity theoretical model for the wave propagation in a partially-saturated medium is presented by combining the extended Gurevich squirt-flow model and White patchy-saturation theory. Numerical simulations are used to analyze wave propagation characteristics that depend on water saturation, external patchy diameter, and viscosity. We consider a tight sandstone from the Qingyang area of the Ordos Basin in west China and perform ultrasonic measurements under partial saturation states and different confining pressures, where the basic properties of the rock are obtained at the full gas saturation. The comparison of experimental data and theoretical modeling results shows a fairly good agreement, indicating that the new theory is effective. [ABSTRACT FROM AUTHOR]

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the 'bang-sensitive' sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABAA blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants. [ABSTRACT FROM AUTHOR]

GCaMP imaging is widely employed for investigating neuronal Ca2+ dynamics. The Drosophila larval neuromuscular junction (NMJ) consists of three distinct types of motor terminals (type Ib, Is and II). We investigated whether variability in synaptic bouton sizes and GCaMP expression levels confound interpretations of GCaMP readouts, in inferring the intrinsic Ca2+ handling properties among these functionally distinct synapses. Analysis of large data sets accumulated over years established the wide ranges of bouton sizes and GCaMP baseline fluorescence, with large overlaps among synaptic categories. We showed that bouton size and GCaMP baseline fluorescence were not confounding factors in determining the characteristic frequency responses among type Ib, Is and II synapses. More importantly, the drastic phenotypes that hyperexcitability mutations manifest preferentially in particular synaptic categories, were not obscured by bouton heterogeneity in physical size and GCaMP expression level. Our data enabled an extensive analysis of the distal-proximal gradient of GCaMP responses upon genetic and pharmacological manipulations. The results illustrate the conditions that disrupt or enhance the distal-proximal gradients. For example, stimulus frequencies just above the threshold level produced the steepest gradient in low Ca2+ (0.1 mM) saline, while supra-threshold stimulation flattened the gradient. Moreover, membrane hyperexcitability mutations (eag1 Sh120 and parabss1) and mitochondrial inhibition by dinitrophenol (DNP) disrupted the gradient. However, a novel distal-proximal gradient of decay kinetics appeared after long-term DNP incubation. We performed focal recording to assess the failure rates in transmission at low Ca2+ levels, which yielded indications of a mild distal-proximal gradient in release probability. [ABSTRACT FROM AUTHOR]

Tethered flies allow studies of biomechanics and electrophysiology of flight control. We performed microelectrode recordings of spikes in an indirect flight muscle (the dorsal longitudinal muscle, DLMa) coupled with acoustic analysis of wing beat frequency (WBF) via microphone signals. Simultaneous electrophysiological recording of direct and indirect flight muscles has been technically challenging; however, the WBF is thought to reflect in a one-to-one relationship with spiking activity in a subset of direct flight muscles, including muscle m1b. Therefore, our approach enables systematic mutational analysis for changes in temporal features of electrical activity of motor neurons innervating subsets of direct and indirect flight muscles. Here, we report the consequences of specific ion channel disruptions on the spiking activity of myogenic DLMs (firing at ∼5 Hz) and the corresponding WBF (∼200 Hz). We examined mutants of the genes enconding: 1) voltage-gated Ca2+ channels ( cacophony, cac), 2) Ca2+-activated K+ channels ( slowpoke, slo), and 3) voltage-gated K+ channels ( Shaker, Sh) and their auxiliary subunits ( Hyperkinetic, Hk and quiver, qvr). We found flight initiation in response to an air puff was severely disrupted in both cac and slo mutants. However, once initiated, slo flight was largely unaltered, whereas cac displayed disrupted DLM firing rates and WBF. Sh, Hk, and qvr mutants were able to maintain normal DLM firing rates, despite increased WBF. Notably, defects in the auxiliary subunits encoded by Hk and qvr could lead to distinct consequences, that is, disrupted DLM firing rhythmicity, not observed in Sh. Our mutant analysis of direct and indirect flight muscle activities indicates that the two motor activity patterns may be independently modified by specific ion channel mutations, and that this approach can be extended to other dipteran species and additional motor programs, such as electroconvulsive stimulation-induced seizures. [ABSTRACT FROM AUTHOR]

Although Obaid Siddiqi's major research focus in neurogenetics was on chemosensation and olfaction in Drosophila, he made seminal contributions to the study of temperature-sensitive paralytic mutants that paved the way for research that we and many other investigators have continued to pursue. Here we recount Siddiqi's investigation and the impact it had on our own studies especially at a formative stage of our careers. We acknowledge our debt to Obaid Siddiqi and remember him fondly as an inspired and inspiring scientist, mentor, role model and human being. [ABSTRACT FROM AUTHOR]

Professors Baruch Minke and William Pak recount the story of their early endeavor to reveal the phototransduction process mediated by the TRP channel in the fruit fly I Drosophila. i This light-sensitive TRP channel is now recognized as the founding member of the TRP channel superfamily, which encompasses a large category of channels underpinning different sensory mechanisms, including visual, auditory, thermal, and mechanosensory transduction. The 2021 Nobel Prize in Medicine and Physiology recognized the seminal work of David Julius, who established the temperature and pain sensory mechanisms based on the TRPV channel, and Ardem Patapoutian, who resolved the stretch activation mechanism for touch and proprietary sensation via Piezo channels. The light-activated TRP channel: The founding member of the TRP channel Superfamily. [Extracted from the article]

The article discusses studies on genetic linkage between between genes, brain, and behavior and establishment of the field of Neurogenetics by isolation of single-gene mutations that disrupt neural traits. Topics include epigenetic remodeling of DNAs, gene mutation of Huntingtin (Htt) causing Huntington's disease and pathogenic mechanisms, and progression of heterogeneous disease, Frontotemporal dementia (FTD) and it's linkage to degenerative disease, amyotrophic lateral sclerosis (ALS).

Folding-induced folding for the construction of artificial hybrid helices from two different kinds of aromatic sequences is described. Linear compounds 1a, 1b, and 2, containing one aromatic amide trimer or pentamer and one or two aromatic 1,2,3-triazole tetramers, have been designed and synthesized. The trimeric and pentameric amide segments are driven by intramolecluar N—H···F hydrogen bonding to adopt a folded or helical conformation, whereas the triazole segment is intrinsically disordered. In organic solvents of low polarity, the amide foldamer segment induces the attached triazole segment(s) to fold through intramolecular stacking, leading to the formation of hybrid helices. The helical conformation of these hybrid sequences has been confirmed by 1H and 19F NMR spectroscopy, UV/Vis spectroscopy, circular dichroism (CD) experiments, and theoretical calculations. It was found that the amide pentamer exhibits a stronger ability to induce the folding of the attached triazole segment(s) compared with that of the shorter trimer. Enantiomers (R)-3 and (S)-3, which contain an R- or S-(1-naphthyl)ethylamino group at the end of a tetraamide segment, have also been synthesized. CD experiments showed that introduction of a chiral group caused the whole framework to produce a strong helicity bias. Densityfunctional- theory calculations on (S)-3 suggested that this compound exists as a right-handed (P) helix. [ABSTRACT FROM AUTHOR]

Abelson tyrosine kinase (Abl) is known to regulate axon guidance, muscle development, and cell-cell interaction in vivo. The Drosophila primary culture system offers advantages in exploring the cellular mechanisms mediated by Abl with utilizing various experimental manipulations. Here we demonstrate that single-embryo cultures exhibit stage-dependent characteristics of cellular differentiation and developmental progression in neurons and myocytes, as well as nerve-muscle contacts. In particular, muscle development critically depends on the stage of dissociated embryos. In wild-type (WT) cultures derived from embryos before stage 12, muscle cells remained within cell clusters and were rarely detected. Interestingly, abundant myocytes were spotted in Abl mutant cultures, exhibiting enhanced myocyte movement and fusion, as well as neuron-muscle contacts even in cultures dissociated from younger, stage 10 embryos. Notably, Abl myocytes frequently displayed well-expanded lamellipodia. Conversely, Abl neurons were characterized with fewer large veil-like lamellipodia, but instead had increased numbers of filopodia and darker nodes along neurites. These distinct phenotypes were equally evident in both homo- and hetero-zygous cultures (Abl/Abl vs. Abl/+) of different alleles (Abl1 and Abl4) indicating dominant mutational effects. Strikingly, in WT cultures derived from stage 10 embryos, high temperature (HT) incubation promoted muscle migration and fusion, partially mimicking the advanced muscle development typical of Abl cultures. However, HT enhanced neuronal growth with increased numbers of enlarged lamellipodia, distinct from the characteristic Abl neuronal morphology. Intriguingly, HT incubation also promoted Abl lamellipodia expansion, with a much greater effect on nerve cells than muscle. Our results suggest that Abl is an essential regulator for myocyte and neuron development and that high-temperature incubation partially mimics the faster muscle development typical of Abl cultures. Despite the extensive alterations by Abl mutations, we observed myocyte fusion events and nerve-muscle contact formation between WT and Abl cells in mixed WT and Abl cultures derived from labeled embryos. [ABSTRACT FROM AUTHOR]

In recent years, the Yanchang shale-oil formations of the Ordos Basin are rich in reserves with complex lithology and structure characteristics, low porosity and low permeability, and weak anomalies for oil and water discriminations, have been the key targets of unconventional oil/gas resource exploration and development in the relevant areas. The joint acoustic-electrical (AE) properties can be used to interpret reservoir lithology, mineralogy, pore structure, and fluid saturation. To conduct tests of thin section analysis, X-ray diffraction, and ultrasonic and electrical experiments at different pressures and saturation degrees, cores from the shale-oil formations in the Q area of the basin are collected. The variations in AE properties with respect to clay content, porosity, pressure (microfracture), and saturation are analyzed. The experimental results indicate that the rock physics behaviors of sandstones with different clay contents vary significantly. The AE properties of clean sandstones are basically dependent on the microfractures (pressure), while for muddy sandstones, the clay content is an important factor affecting the responses. The target reservoir consists of interbedded sandstone and shale layers. The AE equivalent medium equations and the Gurevich theory are applied to establish the joint models for the different lithologies and simulate the variations in AE properties with respect to fluid type, pore structure, and mineral components. The three-dimensional joint templates of clean and muddy sandstones, as well as shale, are developed based on the elastic and electrical attributes and then calibrated using the experimental and well-log data. The reservoir properties are estimated with the templates and validated by the log data. The results indicate that the joint templates based on lithology characteristics can effectively characterize the properties of interbedded sandstone and shale layers. Furthermore, the combined application of AE data provides more beneficial information for the assessment of rock properties, leading to precise estimates that conform with the actual formation conditions. [ABSTRACT FROM AUTHOR]

'Bang-sensitive' mutants of Drosophila display characteristic repertoires of distinct seizure-and-paralysis behaviors upon mechanical shock (Ganetzky & Wu, 1982, Genetics, 100, 597-614). The authors found that each of the bang-sensitive mutants described in this paper ( bas, bss, eas, and tko) also displayed similar behavioral repertoires upon exposure to either high or low temperature. These repertoires are composed of interspersed periods of seizure and paralysis, and appear to have interesting parallels with vertebrate epileptiform behavior. Analysis of gynandromorph mosaics of these bang-sensitive mutant flies indicated that anatomical foci required for these two types of behaviors do not totally overlap, as they were separable among mosaic flies. Observations on mosaic and decapitated flies demonstrated an all-or-none expression of the seizure-and-paralysis behaviors, indicating global activity and long-range interactions in the nervous system. Therefore, the diverse collection of currently available Drosophila bang-sensitive mutants may serve as a rich source for mutational and cellular analysis to identify interacting molecular networks that are responsible for seizure phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: Two classic learning mutants in Drosophila, rutabaga ( rut) and dunce ( dnc), are defective in cyclic adenosine monophosphate (cAMP) synthesis and degradation, respectively, exhibiting a variety of neuronal and behavioral defects. We ask how the opposing effects of these mutations on cAMP levels modify subsets of phenotypes, and whether any specific phenotypes could be ameliorated by biochemical counter balancing effects in dnc rut double mutants. Our study at larval neuromuscular junctions (NMJs) demonstrates that dnc mutations caused severe defects in nerve terminal morphology, characterized by unusually large synaptic boutons and aberrant innervation patterns. Interestingly, a counterbalancing effect led to rescue of the aberrant innervation patterns but the enlarged boutons in dnc rut double mutant remained as extreme as those in dnc. In contrast to dnc, rut mutations strongly affect synaptic transmission. Focal loose-patch recording data accumulated over 4 years suggest that synaptic currents in rut boutons were characterized by unusually large temporal dispersion and a seasonal variation in the amount of transmitter release, with diminished synaptic currents in summer months. Experiments with different rearing temperatures revealed that high temperature (29-30°C) decreased synaptic transmission in rut, but did not alter dnc and wild-type (WT). Importantly, the large temporal dispersion and abnormal temperature dependence of synaptic transmission, characteristic of rut, still persisted in dnc rut double mutants. To interpret these results in a proper perspective, we reviewed previously documented differential effects of dnc and rut mutations and their genetic interactions in double mutants on a variety of physiological and behavioral phenotypes. The cases of rescue in double mutants are associated with gradual developmental and maintenance processes whereas many behavioral and physiological manifestations on faster time scales could not be rescued. We discuss factors that could contribute to the effectiveness of counterbalancing interactions between dnc and rut mutations for phenotypic rescue. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies showed that homocysteine (Hcy) reduces endothelial progenitor cells (EPCs) numbers and impairs functional activity. Atorvastatin, HMG-CoA inhibition has been showed to have protective effects on EPCs. Recent studies have demonstrated that reduced EPCs numbers and activity are associated with EPCs apoptosis. However, the protective mechanisms of atorvastatin on HHcy-induced EPCs apoptosis remain to be determined. This study was designed to examine the effect of atorvastatin on homocysteine-induced reactive oxygen species (ROS) production and apoptosis in EPCs. EPCs were isolated from peripheral blood and characterized, then challenged with Hcy (50–500μmol/L) in the presence or absence of atorvastatin (0.01–1μmol/L) or various stress signaling inhibitors, including mevalonate (100μmol/L), antioxidants N-acetyl cysteine (NAC, 10μmol/L), the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI 10μmol/L), the eNOS inhibitor NGmono-methyl-l-arginine LNMA (1mmol/L), and the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 (10μmol/L). Apoptosis was evaluated by FACS analysis and cell viability was determined by MTT assay. ROS were detected by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFH-DA). NADPH oxidases were evaluated with lucigenin-enhanced chemiluminescence. Expression of Nox4 mRNA and p-p38MAPK protein was measured by RT-PCR and Western blot analysis, respectively. Our data revealed that atorvastatin significantly suppressed Hcy-induced ROS accumulation and EPCs apoptosis. Atorvastatin also antagonized homocysteine-induced activation of NADPH oxidase and overexpression of Nox4 mRNA and p-p38MAPK protein. Similar effects occurred with EPCs transfected with Nox4 siRNA. These findings demonstrated that atorvastatin may inhibit Hcy-induced NADPH oxidase activation, ROS accumulation, and EPCs apoptosis through Nox4/p38MAPK dependent mechanisms, all of which may contribute to atorvastatin-induced beneficial effects on EPCs function. [Copyright &y& Elsevier]

Recent studies have indicated that the Shaker potassium channel regulates sleep in Drosophila. The Drosophila quiver ( qvr) gene encodes a novel potassium channel subunit that modulates the Shaker potassium channel. The Qvr peptide contains a signal sequence for extracellular localization and may regulate a unique feature of the Shaker IA current that confers special neuronal excitability patterns. Thus, studies of the Shaker channel properties in the qvr mutant background should provide an opportunity to uncover a new form of physiologic modulation of potassium channels. We have begun to investigate the impact of qvr protein on the Shaker channel properties and its implications in synaptic function in vivo. We studied synaptic transmission at the larval neuromuscular junction and characterized the transient potassium current IA in larval muscles. We identified two different functional states of IA in qvr larval muscles, as reflected by two distinct components, IAF and IAS, differing in their kinetics of recovery from inactivation and sensitivity to a K+ channel blocker. Correspondingly, qvr mutant larvae exhibit multiple synaptic discharges following individual nerve stimuli during repetitive activity. [ABSTRACT FROM AUTHOR]

Social deprivation is known to trigger a variety of behavioral and physiological modifications in animal species, but the underlying genetic and cellular mechanisms are not fully understood. As we described previously, adult female flies reared in isolation show increased frequency of aggressive behaviors than those reared in a group. Here, we report that isolated rearing also caused significantly altered nerve and muscle excitability and enhanced synaptic transmission at larval neuromuscular junctions (NMJs). We found that mutations of two genes, Hyperkinetic ( Hk) and glutathione S-transferase-S1 ( gsts1), alter the response to social isolation in Drosophila. Hk and gsts1 mutations increased adult female aggression and larval neuromuscular hyperexcitability, even when reared in a group. Unlike wild type, these behavioral and electrophysiological phenotypes were not further enhanced in these mutants by isolated rearing. Products of these two genes have been implicated in reactive oxygen species (ROS) metabolism. We previously reported in these mutants increased signals from an ROS probe at larval NMJs, and this study revealed distinct effects of isolation rearing on these mutants, compared to the control larvae in ROS-probe signals. Our data further demonstrated modified nerve and muscle excitability by a reducing agent, dithiothreitol. Our results suggest that altered cellular ROS regulation can exert pleiotropic effects on nerve, synapse, and muscle functions and may involve different redox mechanisms in different cell types to modify behavioral expressions. Therefore, ROS regulation may take part in the cellular responses to social isolation stress, underlying an important form of neural and behavioral plasticity. [ABSTRACT FROM AUTHOR]

Abstract: We review work in the major model systems for habituation in Drosophila melanogaster, encompassing several sensory modalities and behavioral contexts: visual (giant fiber escape response, landing response); chemical (proboscis extension reflex, olfactory jump response, locomotory startle response, odor-induced leg response, experience-dependent courtship modification); electric (shock avoidance); and mechanical (leg resistance reflex, cleaning reflex). Each model system shows several of Thompson and Spencer’s [Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16–43] parametric criteria for habituation: spontaneous recovery and dishabituation have been described in almost all of them and dependence of habituation upon stimulus frequency and stimulus intensity in the majority. Stimulus generalization (and conversely, the delineation of stimulus specificity) has given insights into the localization of habituation or the neural architecture underlying sensory processing. The strength of Drosophila for studying habituation is the range of genetic approaches available. Mutations have been used to modify specific neuroanatomical structures, ion channels, elements of synaptic transmission, and second-messenger pathways. rutabaga and dunce, genes of the cAMP signal pathway that have been studied most often in the reviewed experiments, have also been implicated in synaptic plasticity and associative conditioning in Drosophila and other species including mammals. The use of the Gal4/UAS system for targeting gene expression has enabled genetic perturbation of defined sets of neurons. One clear lesson is that a gene may affect habituation differently in different behaviors, depending on the expression, processing, and localization of the gene product in specific circuits. Mutations of specific genes not only provide links between physiology and behavior in the same circuit, but also reveal common mechanisms in different paradigms of behavioral plasticity. The rich repertoire of models for habituation in the fly is an asset for combining a genetic approach with behavioral, anatomical and physiological methods with the promise of a more complete understanding. [Copyright &y& Elsevier]

Abstract: Although modulation of presynaptic terminal excitability can profoundly affect transmission efficacy, how excitability along axonal terminal branches is regulated requires further investigations. We performed focal patch recording in Drosophila larval neuromuscular junctions (NMJs) to monitor the activity of individual synaptic boutons along the presynaptic terminal. Analysis of the learning mutant rutabaga (rut) suggests a tight regulation of presynaptic terminal excitability by rut adenylyl cyclase (AC) that is responsible for Ca2+/calmodulin-dependent cAMP synthesis. Focal excitatory junctional currents (ejcs) demonstrated that disrupted cAMP metabolism in rut mutant boutons leads to decreased transmitter release, coupled with temporal dispersion and amplitude fluctuation of ejcs during repetitive activity. Strikingly, rut motor terminals displayed greatly increased variability among corresponding terminal branches of identified NMJs in different preparations. However, boutons throughout single terminal branches were relatively uniform in either WT or rut mutant larvae. The use of electrotonic depolarization to directly evoke transmitter release from axonal terminals revealed that variability in neurotransmission originated from varying degrees of weakened excitability in rut terminals. Pharmacological treatments and axonal action potential recordings raised the possibility that defective rut AC resulted in reduced Ca2+ currents in the nerve terminal. Thus, our data indicate that rut AC not only affects transmitter release machinery, but also plays a previously unsuspected role in local excitability control, both contributing to transmission level and precision along the entire axonal terminal. [ABSTRACT FROM AUTHOR]

The Drosophila Hyperkinetic (Hk) gene encodes a β subunit of Shaker (Sh) K+ channels and shows high sequence homology to aldoketoreductase. Hk mutations are known to modify the voltage dependence and kinetics of Sh currents, which are also influenced by the oxidative state of the N-terminus region of the Sh channel, as demonstrated in heterologous expression experiments in frog oocytes. However, an in vivo role of Hk in cellular reduction/oxidation (redox) has not been demonstrated. By using a fluorescent indicator of reactive oxygen species (ROS), dihydrorhodamine-123 (DHR), we show that the presynaptic nerve terminal of larval motor axons is metabolically active, with more rapid accumulation of ROS in comparison with muscle cells. In Hk terminals, DHR fluorescence was greatly enhanced, indicating increased ROS levels. This observation implicates a role of the Hk β subunit in redox regulation in presynaptic terminals. This phenomenon was paralleled by the expected effects of the mutations affecting glutathione S-transferase S1 as well as applying H2O2 to wild-type synaptic terminals. Thus, our results also establish DHR as a useful tool for detecting ROS levels in the Drosophila neuromuscular junction. [ABSTRACT FROM AUTHOR]

Abstract: Y1−x BO3:xTb3+ phosphors were first synthesized by hydrothermal reaction, and the samples were characterized by X-ray powder diffractometry, infrared absorption, nuclear magnetic resonance, scanning electron microscopy and photoluminescence. The results show that single phase is obtained with Tb concentration up to 0.28 and all the samples exhibit flake-like morphology. The sample was determined to be vaterite-type orthoborate and the boron is both four-coordinated (chief) and three-coordinated (few). The Y1−x BO3:xTb3+ phosphors showed intense green emission at 550nm and the intensity of the emission increases with Tb3+ substitution up to 0.22 and then decreases for higher Tb3+ content. In the phosphors prepared by the hydrothermal method the concentration quenching is higher than in the phosphors prepared by solid-state reaction; the intensity of emission is stronger in the former than that of the latter. Y1−x BO3:xTb3+ is a promising phosphor for plasma display panels and hydrargyrum-free lamps. [Copyright &y& Elsevier]

The RNA-binding protein, Boule is conserved across species and is required for male fertility. Boule and the DAZ homologues in mice and humans appear specific to the testis. Boule functions in spermatogenesis by controlling the translation of the meiotic cell division cycle 25 (Cdc25) phosphatase, Twine. Here we show, for the first time, a function for the DAZ protein, Boule, outside of meiosis. We found that an isoform of Boule is expressed in the nervous system and when its expression is increased we observe mutant phenotypes in neural communication between the receptor and laminar cells of the fly eye, altered larval locomotion and when further overexpressed, viability. As in the germ line, genetic studies indicate that Boule functions in the Cdc25 phosphatase pathway in the nervous system. In a sensitized genetic background of Boule overexpression, we added a loss-of-function mutation of twine and demonstrated a role for Twine Cdc25, in the adult nervous system. Our results indicate that isoforms of boule are expressed outside of the male germ line and that these isoforms have a role in neural function, unlike the boule testis-specific isoform. [ABSTRACT FROM AUTHOR]

A new method for characterizing fiber bending flexibility was developed by worm-like chain model proposed by Kratky-Porod,[1] which was first introduced to the pulp and paper field in this study. For the three types of pulps, the experimental results were compared with the KP chain model, and the resulting determination coefficients were all above 0.95, which proved that the model was feasible to be applied to these three fibers. The relation between fiber bending rigidity and that of cellulosic chains inside was discussed to deduce the fiber bending flexibility. The flexibility of an individual fiber can be approximated as the contribution of that of all the cellulose chains inside. By this method, the fiber flexibility values were determined to be in the range of 0.6×1011−3.5×1011 N−1·m−2, which was comparable to that of the conventional methods recorded in the literature. [ABSTRACT FROM AUTHOR]

A chiral supramolecular alternate block copolymer has been self-assembled from a ureidopyrimidinone (UPy)-terminated arylamide-based hydrogen bonded foldamer and a structurally flexible pentamer, which is driven by the ion-pair binding of the two arylamide segments toward chiral ammonium and carboxylate guests. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various reports published within the issue, including one on light-regulated phosphoproteins, one on seizures and paralytic behaviors associated with Drosophila bang-sensitive mutants, and another on the gene required for rhodopsin maturation.

The article ponders on the origins of neurogenetics. It cites the reasons for publishing a special retrospective issue of the "Journal of Neurogenetics." It mentions the topics that will be published by the journal. It enumerates the changes in the presentation and mechanisms of access to the journal.

An introduction is presented in which the editor discusses various reports within the issue on topics including neurodegenerative diseases, brain diseases and concept of neurogenetics.

The article focuses on the argument regarding the usage of liquidity and clearing as alternative principles for the reform of international money policy. Cited is the currency rule settled during the Monetary and Financial Conference conducted by the United Nations in Bretton Woods, New Hampshire in 1944. The issue regarding the Bretton Woods System as an international monetary system is also tackled

In Drosophila, high-frequency electrical stimulation across the brain triggers a highly stereotypic repertoire of spasms. These electroconvulsive seizures (ECS) manifest as distinctive spiking discharges across the nervous system and can be stably assessed throughout the seizure repertoire in the large indirect flight muscles dorsal longitudinal muscles (DLMs) to characterize modifications in seizure-prone mutants. However, the relationships between ECS-spike patterns and native motor programs, including flight and grooming, are not known and their similarities and distinctions remain to be characterized. We employed quantitative spike pattern analyses for the three motor patterns including: (1) overall firing frequency, (2) spike timing between contralateral fibers, and (3) short-term variability in spike interval regularity (CV2) and instantaneous firing frequency (ISI−1). This base-line information from wild-type (WT) flies facilitated quantitative characterization of mutational effects of major neurotransmitter systems: excitatory cholinergic (Cha), inhibitory GABAergic (Rdl) and electrical (ShakB) synaptic transmission. The results provide an initial glimpse on the vulnerability of individual motor patterns to different perturbations. We found marked alterations of ECS discharge spike patterns in terms of either seizure threshold, spike frequency or spiking regularity. In contrast, no gross alterations during grooming and a small but noticeable reduction of firing frequency during Rdl mutant flight were found, suggesting a role for GABAergic modulation of flight motor programs. Picrotoxin (PTX), a known pro-convulsant that inhibits GABAA receptors, induced DLM spike patterns that displayed some features, e.g. left-right coordination and ISI−1 range, that could be found in flight or grooming, but distinct from ECS discharges. These quantitative techniques may be employed to reveal overlooked relationships among aberrant motor patterns as well as their links to native motor programs. [ABSTRACT FROM AUTHOR]

The article introduces various papers published within the issue including Gert Pflugfelder's review of the story about the optomotor-blind gene, and another about the interaction between neuroglian and semaphorin 1a.

A preface for the July 2008 issue of the "Journal of Neurogenetics" is presented.

Several photographs of retired professor Barry Ganetzky are presented including his lecture at Tsinghua University in Beijing, China in 2013, his magic trick in 2016, and at a conference in 1980.

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various articles within the issue on topics including ontogeny, genetic model animals and specific behaviours and the neural circuits.

The hemolymph-like HL3 saline(Stewart et al., 1994)and standard saline(Jan & Jan, 1976)are two widely used bathing solutions for physiological recordings at theDrosophilalarval neuromuscular junction. It has been established that longevity of larval preparations is better maintained in HL3 saline. However, HL3 can produce results that are inconsistent with previous findings in standard saline, particularly on temperature sensitivity and membrane excitability phenotypes. In wild-type larvae, the excitatory junctional potentials(EJPs)in standard saline(containing 4  mM Mg 2+ and 1.8  mM Ca 2+ )were not blocked by a temperature increase up to 39–40°C, consistent with unimpaired larval locomotion below these temperatures. However, in HL3 saline(containing 20  mM Mg 2+ and 1.5  mM Ca 2+ ), EJPs were blocked at 30°C. As for temperature-sensitive mutantsnap ts andpara ts , the EJP-blocking temperatures were decreased from about 29 and 33°C in standard saline to about 23 and 26°C in HL3, respectively. Compound action potential recordings confirmed that segmental nerve action potentials were more readily blocked by a temperature increase in HL3 than in standard saline. Axonal excitability was suppressed in HL3 even at room temperatures, as evidenced by a lengthened refractory period in wild-type larvae. Similar suppression occurred for the hyper-excitable double mutanteag Sh, which maintained high-frequency spontaneous EJPs in standard saline but showed a rapidly declining EJP frequency in HL3. Application of HL3 saline also strongly suppressed the prolonged transmitter release following removal of repolarization mechanisms by K + channel blockers or by theeag Shmutation previously described in standard saline. These discrepancies suggest that the high divalent cation content in HL3 may confer a surface charge screening effect to suppress nerve membrane excitability. We found that a minimal adjustment of the HL3 saline, decreasing the Mg 2+ ion concentration from 20 to 4  mM, was sufficient to resolve the discrepancies. While retaining the longevity of the larval neuromuscular preparation, the modified HL3 saline(HL3.1)restored the established wild-type EJP properties as well as phenotypes of several widely used temperature-sensitive and hyper-excitable mutants previously documented in standard saline. [ABSTRACT FROM AUTHOR]

The Drosophila mutant paraShu harbors a dominant, gain-of-function allele of the voltage-gated sodium channel gene, paralytic (para). The mutant flies display severe seizure-like phenotypes, including neuronal hyperexcitability, spontaneous spasms, ether-induced leg shaking, and heat-induced convulsions. We unexpectedly found that two distinct food recipes used routinely in the Drosophila research community result in a striking difference in severity of the paraShu phenotypes. Namely, when paraShu mutants were raised on the diet originally formulated by Edward Lewis in 1960, they showed severe neurological defects as previously reported. In contrast, when they were raised on the diet developed by Frankel and Brousseau in 1968, these phenotypes were substantially suppressed. Comparison of the effects of these two well-established food recipes revealed that the diet-dependent phenotypic suppression is accounted for by milk whey, which is present only in the latter. Inclusion of milk whey in the diet during larval stages was critical for suppression of the adult paraShu phenotypes, suggesting that this dietary modification affects development of the nervous system. We also found that milk whey has selective effects on other neurological mutants. Among the behavioral phenotypes of different para mutant alleles, those of paraGEFS+ and parabss were suppressed by milk whey, while those of paraDS and parats1 were not significantly affected. Overall, our study demonstrates that different diets routinely used in Drosophila labs could have considerably different effects on neurological phenotypes of Drosophila mutants. This finding provides a solid foundation for further investigation into how dietary modifications affect development and function of the nervous system and, ultimately, how they influence behavior. [ABSTRACT FROM AUTHOR]

Our earlier genetic screen uncovered a paraquat-sensitive leg-shaking mutantquiver1(qvr1), whose gene product interacts with theShaker(Sh) K+channel. We also mapped theqvrlocus to EY04063 and noticed altered day–night activity patterns in these mutants. Such circadian behavioral defects were independently reported by another group, who employed theqvr1allele we supplied them, and attributed the extreme restless phenotype of EY04063 to theqvrgene. However, their report adopted a new noncanonical gene namesleepless(sss) forqvr. In addition toqvr1andqvrEY, our continuous effort since the early 2000s generated a number of novel recessiveqvralleles, including ethyl methanesulfonate (EMS)-induced mutationsqvr2andqvr3, and P-element excision linesqvrip6(imprecise jumpout),qvrrv7, andqvrrv9(revertants) derived fromqvrEY. Distinct from the original intron-locatedqvr1allele that generates abnormal-sized mRNAs,qvr2, andqvr3had their lesion sites in exons 6 and 7, respectively, producing nearly normal-sized mRNA products. A set of RNA-editing sites are nearby the lesion sites ofqvr3andqvrEYon exon 7. Except for the revertants, allqvralleles display a clear ether-induced leg-shaking phenotype just likeSh, and weakened climbing abilities to varying degrees. UnlikeSh, all shakingqvralleles (except forqvrf01257) displayed a unique activity-dependent enhancement in excitatory junction potentials (EJPs) at larval neuromuscular junctions (NMJs) at very low stimulus frequencies, withqvrEYdisplaying the largest EJP and more significant NMJ overgrowth than other alleles. Our detailed characterization of a collection ofqvralleles helps to establish links between novel molecular lesions and different behavioral and physiological consequences, revealing how modifications of theqvrgene lead to a wide spectrum of phenotypes, including neuromuscular hyperexcitability, defective motor ability and activity-rest cycles. [ABSTRACT FROM PUBLISHER]

Vernalization is classically defined as the induction of flowering process by exposure of the plants to a prolonged cold condition. Normally, it is considered as a precondition of flowering. Vicia faba, commonly known as faba bean, belongs to family Fabaceae. It is one of the plant species that has been cultivated in the earliest human settlements. In this study, an iTRAQ-LC-MS/MS-based quantitative proteomic analysis has been conducted to compare the vernalized faba bean seedlings and its corresponding control. In total, 91 proteins from various functional categories were observed to be differentially accumulated in vernalized faba bean seedlings. Subsequent gene ontology analysis indicated that several biological processes or metabolic pathways including photosynthesis and phytic acid metabolism were differentially respond to vernalization in comparison to the control sample. Further investigation revealed that a family of proteins nominated as glycine-rich RNA-binding factor was accumulated in vernalized seedlings, indicating an extra layer of regulation by alternative splicing on transcript abundance in response to vernalization. These findings raise a possibility that these candidate proteins could be important to represent the responsive network under vernalization process. Therefore, we propose that the regulation of vernalization in faba bean not only occurs at the transcriptional level as previously reported, but also at the post-transcriptional level. [ABSTRACT FROM AUTHOR]

Intrinsic electric activities of neurons play important roles in establishing and refining neural circuits during development. However, how the underlying ionic currents undergo postembryonic reorganizations remains largely unknown. Using acutely dissociated neurons from larval, pupal, and adultDrosophilabrains, we show drastic re-assemblies and compensatory regulations of voltage-gated (IKv) and Ca2+-activated (IK(Ca)) K+ currents during postembryonic development. Larval and adult neurons displayed prominent fast-inactivating IKv, mediated by theShaker(Sh) channel to a large extent, while in the same neurons IK(Ca)was far smaller in amplitude. In contrast, pupal neurons were characterized by large sustained IKvand prominent IK(Ca), encoded predominantly by theslowpoke(slo) gene. Surprisingly, deletion ofShin theShMnull mutant removed inactivating, transient IKvfrom large portions of neurons at all stages. Interestingly, elimination ofShcurrents was accompanied by upregulation of non-Shtransient IKv. In comparison, theslo1mutation abolished the vast majority of IK(Ca), particularly at the pupal stage. Strikingly, the deficiency of IK(Ca)inslopupae was compensated by the transient component of IKvmediated byShchannels. Thus, IK(Ca)appears to play critical roles in pupal development and its absence induces functional compensations from a specific transient IKvcurrent. While mutants lacking eitherShorslocurrents survived normally,Sh;;slodouble mutants deficient in both failed to survive through pupal metamorphosis. Together, our data highlight significant reorganizations and homeostatic compensations of K+ currents during postembryonic development and uncover previously unrecognized roles forShandsloin this plastic process. [ABSTRACT FROM AUTHOR]

The article explores the contribution of Professor Yoshiki Hotta to the field of neurogenetics. It recalls the work of Hotta on muscle physiology research. It discusses the interest of Hotta in performing studies on brain functions. In addition, the article remembers the return of Hotta to Japan in 1972 to establish his own laboratory in the Department of Physics at the University of Tokyo.

An introduction to the journal is presented in which the editors feature physicist Erich Buchner, discuss an article on the role of Hox genes in regulating the morphogenesis of motorneurons and acknowledge Buchner's contribution to the field of Drosophila neuroscience.

Room-temperature negative differential resistance (NDR) has been observed in different types of organic materials. However, detailed study on the influence of the organic material on NDR performance is still scarce. In this work, room-temperature NDR is observed when CdSe quantum dot (QD) modified ITO is used as the electrode. Furthermore, material dependence of the NDR performance is observed by selecting materials with different charge transporting properties as the active layer, respectively. A peak-to-valley current ratio up to 9 is observed. It is demonstrated that the injection barrier between ITO and the organic active layer plays a decisive role for the device NDR performance. The influence of the aggregation state of CdSe QDs on the NDR performance is also studied, which indicates that the NDR is caused by the resonant tunneling process in the ITO/CdSe QD/organic active layer structure. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that theneurobeachin(NBEA) gene is disrupted in human patients with idiopathic autism (Castermans et al., 2003). TheNBEAgene spans the common fragile site FRA 13A and encodes a signal scaffold protein (Savelyeva et al., 2006). In mice,NBEAhas been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. (Medrihan et al., 2009; Savelyeva et al., 2006).Rugose (rg)is theDrosophilahomolog of the mammalian and humanNBEA. Our previous genetic and molecular analyses have shown thatrgencodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways (Shamloula et al., 2002). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adultrgloss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate thatDrosophila NBEA(rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs. [ABSTRACT FROM PUBLISHER]

Voltage-gated sodium channels (Na v channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster , besides the canonical Na v channel, Para (also called DmNa v ), there is a sodium channel-like cation channel called DSC1 ( Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNa v ( para ts ) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNa v and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNa v / DSC1 double mutant line by introducing a para ts1 allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNa v variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNa v channel. Furthermore, we found that I265N-mediated pyrethroid resistance in para ts1 mutant flies was almost completely abolished in para ts1 ; DSC1 −/− double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies ( w 1118A ), and the para ts1 ; DSC1 −/− double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para ts1 mutant. Our findings revealed distinct roles of the DmNa v and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss various articles within the issue on topics including Drosophila genetics, micro RNA (miRNA) response in alcohol treatment in flies, and the role of Huntingtin protein in neurons.