Motion as a phenotype: the use of live-cell imaging and machine visual screening to characterize transcription-dependent chromosome dynamics

BACKGROUND: Gene transcriptional activity is well correlated with intra-nuclear position, especially relative to the nuclear periphery, which is a region classically associated with gene silencing. Recently however, actively transcribed genes have also been found localized to the nuclear periphery in the yeast Saccharomyces cerevisiae. When genes are activated, they become associated with the nuclear pore complex (NPC) at the nuclear envelope. Furthermore, chromosomes are not static structures, but exhibit constrained diffusion in real-time, live-cell studies of particular loci. The relationship of chromosome motion with transcriptional activation and active-gene recruitment to the nuclear periphery has not yet been investigated. RESULTS: We have generated a yeast strain that enables us to observe the motion of the galactose-inducible GAL gene locus relative to the nuclear periphery in real-time under transcriptionally active and repressed conditions. Using segmented geometric particle tracking, we show that the repressed GAL locus undergoes constrained diffusive movement, and that transcriptional induction with galactose is associated with an enrichment in cells with GAL loci that are both associated with the nuclear periphery and much more constrained in their movement. Furthermore, we report that the mRNA export factor Sac3 is involved in this galactose-induced enrichment of GAL loci at the nuclear periphery. In parallel, using a novel machine visual screening technique, we find that the motion of constrained GAL loci correlates with the motion of the cognate nuclei in galactose-induced cells. CONCLUSION: Transcriptional activation of the GAL genes is associated with their tethering and motion constraint at the nuclear periphery. We describe a model of gene recruitment to the nuclear periphery involving gene diffusion and the mRNA export factor Sac3 that can be used as a framework for further experimentation. In addition, we applied to the analysis of chromosome motion a machine visual screening approach that used unbiased visual data rather than segmented geometric data. This novel analytical approach will allow for high-throughput study of processes that can be monitored via alterations in chromosome motion and connectivity with the nuclear periphery

Gaming and gaming disorder: a mediation model gender, salience, age of gaming onset, and time spent gaming

Females in empirically based peer-reviewed studies of Internet gaming disorder (IGD) are underrepresented, despite evidence that there are only minor gender disparities present in online gaming. Moreover, few studies have specifically evaluated adult gender effects, within a formal diagnosis of IGD, and behavioral motivation, as defined by the reinforcing behavioral function. A mediation analysis evaluated the relationship between gender, behavioral motivation, and the diagnostic features in online gaming among adults to understand the impact of motivation on videogame playing. This study interviewed 304 adults (aged >18 years) in which 178 identified as female. Participants completed the Video Game Functional Assessment-Revised (VGFA-R) and the 20-item Internet Gaming Disorder Test (IGDT-20) through an online survey. Results showed that number of hours played per week, and subfactors of the VGFA-R differed between gender, indicating that the function and the maintaining of videogame play are essential in evaluating videogame addiction. These findings support and extend the literature's limited findings concerning gender and online gaming

Simplicial quantum dynamics

Present-day quantum field theory can be regularized by a decomposition into quantum simplices. This replaces the infinite-dimensional Hilbert space by a high-dimensional spinor space and singular canonical Lie groups by regular spin groups. It radically changes the uncertainty principle for small distances. Gaugeons, including the gravitational, are represented as bound fermion-pairs, and space-time curvature as a singular organized limit of quantum non-commutativity. Keywords: Quantum logic, quantum set theory, quantum gravity, quantum topology, simplicial quantization.Comment: 25 pages. 1 table. Conference of the International Association for Relativistic Dynamics, Taiwan, 201

DEG/ENaC but Not TRP Channels Are the Major Mechanoelectrical Transduction Channels in a C. elegans Nociceptor

SummaryMany nociceptors detect mechanical cues, but the ion channels responsible for mechanotransduction in these sensory neurons remain obscure. Using in vivo recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as the major mechanotransduction channel in ASH, a polymodal nociceptor in Caenorhabditis elegans. But DEG-1 is not the only mechanotransduction channel in ASH: loss of deg-1 revealed a minor current whose properties differ from those expected of DEG/ENaC channels. This current was independent of two TRPV channels expressed in ASH. Although loss of these TRPV channels inhibits behavioral responses to noxious stimuli, we found that both mechanoreceptor currents and potentials were essentially wild-type in TRPV mutants. We propose that ASH nociceptors rely on two genetically distinct mechanotransduction channels and that TRPV channels contribute to encoding and transmitting information. Because mammalian and insect nociceptors also coexpress DEG/ENaCs and TRPVs, the cellular functions elaborated here for these ion channels may be conserved

Bridged Carbon Fabric Membrane with Boosted Performance in AC Line Filtering Capacitors

High frequency responsive capacitors with lightweight, flexibility, and miniaturization are among the most vital circuit components because they can be readily incorporated into various portable devices to smooth out the ripples for circuits. Electrode materials no doubt are at the heart of such devices. Despite tremendous efforts and recent advances, the development of flexible and scalable high frequency responsive capacitor electrodes with superior performance remains a great challenge. Herein, a straightforward and technologically relevant method is reported to manufacture a carbon fabric membrane glued by nitrogen doped nanoporous carbons produced through a polyelectrolyte complexation induced phase separation strategy. The as obtained flexible carbon fabric bearing a unique hierarchical porous structure, and high conductivity as well as robust mechanical properties, serves as the free standing electrode materials of electrochemical capacitors. It delivers an ultrahigh specific areal capacitance of 2632 F cm amp; 8722;2 at 120 Hz with an excellent alternating current line filtering performance, fairly higher than the state of the art commercial ones. Together, this system offers the potential electrode material to be scaled up for AC line filtering capacitors at industrial level

Rheological Characteristics of Municipal Thickened Excess Activated Sludge (TEAS): Impacts of pH, Temperature, Solid Concentration and Polymer Dose

Rheological characterization of sludge is known to be an essential tool to optimize flow, mixing and other process parameters in wastewater treatment plants. This study deals with the characterization of thickened excess activated sludge in comparison to raw primary sludge and excess activated sludge. The effects of key parameters (total solid concentration, temperature, and pH) on the rheology and flow behavior of thickened excess activated sludge were studied. The rheological investigations were carried out for total solid concentration range of 0.9–3.7 %w/w, temperature range of 23–55 °C, and pH range of 3.6–10.0. Different rheological model equations were fitted to the experimental data. The model equations with better fitting were used to calculate the yield stress, apparent, zero-rate, infinite-rate viscosities, flow consistency index, and flow index. The decrease in concentration from 3.7 to 3.1 %w/w resulted in a drastic reduction of yield stress from 27.6 to 11.0 Pa, while a further reduction of yield stress to 1.3 Pa was observed as solid concentration was reduced to 1.3 %w/w. The viscosity at higher shear rate (>600 s−1) decreased from 0.05 Pa·s down to 0.008 Pa·s when the total solid concentration was reduced from 3.7 to 0.9 %. Yield stress decreased from 20.1 Pa down to 8.3 Pa for the Bingham plastic model when the temperature was raised from 25 to 55 °C. Activation energy and viscosity also showed decreasing trends with increasing temperature. Yield stress of thickened excess activated sludge increased from a value of 6.0 Pa to 8.3 Pa when the pH was increased from 3.6 to 10.0. The effect of polymer dose on the rheological behavior of the thickening of excess activated sludge was also investigated, and the optimum polymer dosage for enhanced thickener performance was determined to be 1.3 kg/ton DS

Prx1 Expressing Cells Are Required for Periodontal Regeneration of the Mouse Incisor

Previous studies have shown that post-natal skeletal stem cells expressing Paired-related homeobox 1 (PRX1 or PRRX1) are present in the periosteum of long bones where they contribute to post-natal bone development and regeneration. Our group also identified post-natal PRX1 expressing cells (pnPRX1+ cells) in mouse calvarial synarthroses (sutures) and showed that these cells are required for calvarial bone regeneration. Since calvarial synarthroses are similar to dentoalveolar gomphosis (periodontium) and since there is no information available on the presence or function of pnPRX1+ cells in the periodontium, the present study aimed at identifying and characterizing pnPRX1+ cells within the mouse periodontium and assess their contribution to periodontal development and regeneration. Here we demonstrated that pnPRX1+ cells are present within the periodontal ligament (PDL) of the mouse molars and of the continuously regenerating mouse incisor. By means of diphtheria toxin (DTA)-mediated conditional ablation of pnPRX1+ cells, we show that pnPRX1+ cells contribute to post-natal periodontal development of the molars and the incisor, as ablation of pnPRX1+ cells in 3-days old mice resulted in a significant enlargement of the PDL space after 18 days. The contribution of pnPRX1+ cells to periodontal regeneration was assessed by developing a novel non-critical size periodontal defect model. Outcomes showed that DTA-mediated post-natal ablation of pnPRX1+ cells results in lack of regeneration in periodontal non-critical size defects in the regeneration competent mouse incisors. Importantly, gene expression analysis of these cells shows a profile typical of quiescent cells, while gene expression analysis of human samples of periodontal stem cells (PDLSC) confirmed that Prx1 is highly expressed in human periodontium. In conclusion, pnPRX1+ cells are present within the continuously regenerating PDL of the mouse incisor, and at such location they contribute to post-natal periodontal development and regeneration. Since this study further reports the presence of PRX1 expressing cells within human periodontal ligament, we suggest that studying the mouse periodontal pnPRX1+ cells may provide significant information for the development of novel and more effective periodontal regenerative therapies in humans

Anxiety Disorders and Sensory Over-Responsivity in Children with Autism Spectrum Disorders: Is There a Causal Relationship?

Anxiety disorders and sensory over-responsivity (SOR) are common in children with autism spectrum disorders (ASD), and there is evidence for an association between these two conditions. Currently, it is unclear what causal mechanisms may exist between SOR and anxiety. We propose three possible theories to explain the association between anxiety and SOR: (a) SOR is caused by anxiety; (b) Anxiety is caused by SOR; or (c) SOR and anxiety are causally unrelated but are associated through a common risk factor or diagnostic overlap. In this paper, we examine support for each theory in the existing anxiety, autism, and neuroscience literature, and discuss how each theory informs choice of interventions and implications for future studies

Single-Unit Activity in the Medial Prefrontal Cortex during Immediate and Delayed Extinction of Fear in Rats

Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit

Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study

Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N = 28; age- and gender-matched comparison group, N = 19) at baseline and 3-year follow-up (MDD group, N = 19; comparison group, N = 17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by highperformance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine–glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression