Stochastic theory of large-scale enzyme-reaction networks: Finite copy number corrections to rate equation models

Chemical reactions inside cells occur in compartment volumes in the range of atto- to femtolitres. Physiological concentrations realized in such small volumes imply low copy numbers of interacting molecules with the consequence of considerable fluctuations in the concentrations. In contrast, rate equation models are based on the implicit assumption of infinitely large numbers of interacting molecules, or equivalently, that reactions occur in infinite volumes at constant macroscopic concentrations. In this article we compute the finite-volume corrections (or equivalently the finite copy number corrections) to the solutions of the rate equations for chemical reaction networks composed of arbitrarily large numbers of enzyme-catalyzed reactions which are confined inside a small sub-cellular compartment. This is achieved by applying a mesoscopic version of the quasi-steady state assumption to the exact Fokker-Planck equation associated with the Poisson Representation of the chemical master equation. The procedure yields impressively simple and compact expressions for the finite-volume corrections. We prove that the predictions of the rate equations will always underestimate the actual steady-state substrate concentrations for an enzyme-reaction network confined in a small volume. In particular we show that the finite-volume corrections increase with decreasing sub-cellular volume, decreasing Michaelis-Menten constants and increasing enzyme saturation. The magnitude of the corrections depends sensitively on the topology of the network. The predictions of the theory are shown to be in excellent agreement with stochastic simulations for two types of networks typically associated with protein methylation and metabolism.Comment: 13 pages, 4 figures; published in The Journal of Chemical Physic

Purification and Analysis of Nucleotides and Nucleosides from Plants

This protocol describes necessary steps to isolate and quantify nucleotides and nucleosides from plant samples. Proper sample preparation in combination with liquid chromatography coupled to mass spectrometry enables the sensitive detection and quantification of metabolites of low abundance. Utilizing a liquid–liquid extraction in combination with a weak anion-exchange solid phase extraction enables the separation of negatively charged molecules from uncharged metabolites or cations

Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS):a randomized, monocentric clinical trial

Background Aim of the study was assessment of efficacy and safety of transcutaneous stimulation of the auricular branch of the vagal nerve (t-VNS) in the treatment of chronic migraine. Methods A monocentric, randomized, controlled, double-blind study was conducted. After one month of baseline, chronic migraine patients were randomized to receive 25 Hz or 1 Hz stimulation of the sensory vagal area at the left ear by a handhold battery driven stimulator for 4 h/day during 3 months. Headache days per 28 days were compared between baseline and the last month of treatment and the number of days with acute medication was recorded The Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires were used to assess headache-related disability. Results Of 46 randomized patients, 40 finished the study (per protocol). In the per protocol analysis, patients in the 1 Hz group had a significantly larger reduction in headache days per 28 days than patients in the 25 Hz group (−7.0 ± 4.6 vs. −3.3 ± 5.4 days, p = 0.035). 29.4 % of the patients in the 1 Hz group had a ≥50 % reduction in headache days vs. 13.3 % in the 25 Hz group. HIT-6 and MIDAS scores were significantly improved in both groups, without group differences. There were no serious treatment-related adverse events. Conclusion Treatment of chronic migraine by t-VNS at 1 Hz was safe and effective. The mean reduction of headache days after 12 weeks of treatment exceeded that reported for other nerve stimulating procedures

Gesture's body orientation modulates the N400 for visual sentences primed by gestures

Body orientation of gesture entails social‐communicative intention, and may thus influence how gestures are perceived and comprehended together with auditory speech during face‐to‐face communication. To date, despite the emergence of neuroscientific literature on the role of body orientation on hand action perception, limited studies have directly investigated the role of body orientation in the interaction between gesture and language. To address this research question, we carried out an electroencephalography (EEG) experiment presenting to participants (n = 21) videos of frontal and lateral communicative hand gestures of 5 s (e.g., raising a hand), followed by visually presented sentences that are either congruent or incongruent with the gesture (e.g., “the mountain is high/low…”). Participants underwent a semantic probe task, judging whether a target word is related or unrelated to the gesture‐sentence event. EEG results suggest that, during the perception phase of handgestures, while both frontal and lateral gestures elicited a power decrease in both the alpha (8–12 Hz) and the beta (16–24 Hz) bands, lateral versus frontal gestures elicited reduced power decrease in the beta band, source‐located to the medial prefrontal cortex. For sentence comprehension, at the critical word whose meaning is congruent/incongruent with the gesture prime, frontal gestures elicited an N400 effect for gesture‐sentence incongruency. More importantly, this incongruency effect was significantly reduced for lateral gestures. These findings suggest that body orientation plays an important role in gesture perception, and that its inferred social‐communicative intention may influence gesture‐language interaction at semantic level

‘‘Lozenge’’ contour plots in scattering from polymer networks

We present a consistent explanation for the appearance of “lozenge” shapes in contour plots of the two dimensional scattering intensity from stretched polymer networks. By explicitly averaging over quenched variables in a tube model, we show that lozenge patterns arise as a result of chain material that is not directly deformed by the stretch. We obtain excellent agreement with experimental data

Antagonism between brain regions relevant for cognitive control and emotional memory facilitates the generation of humorous ideas

The ability to generate humor gives rise to positive emotions and thus facilitate the successful resolution of adversity. Although there is consensus that inhibitory processes might be related to broaden the way of thinking, the neural underpinnings of these mechanisms are largely unknown. Here, we use functional Magnetic Resonance Imaging, a humorous alternative uses task and a stroop task, to investigate the brain mechanisms underlying the emergence of humorous ideas in 24 subjects. Neuroimaging results indicate that greater cognitive control abilities are associated with increased activation in the amygdala, the hippocampus and the superior and medial frontal gyrus during the generation of humorous ideas. Examining the neural mechanisms more closely shows that the hypoactivation of frontal brain regions is associated with an hyperactivation in the amygdala and vice versa. This antagonistic connectivity is concurrently linked with an increased number of humorous ideas and enhanced amygdala responses during the task. Our data therefore suggests that a neural antagonism previously related to the emergence and regulation of negative affective responses, is linked with the generation of emotionally positive ideas and may represent an important neural pathway supporting mental health

Schizotypy and mentalizing: An fMRI study

Introduction: Schizotypy is a personality trait characterized by subclinical schizophrenia symptoms. Individuals with schizophrenia typically display behavioral mentalizing deficits and altered neural correlates during mentalizing. While schizotypy has been inconsistently related to behavioral mentalizing skills, its neural correlates of mentalizing are understudied so far. With this study we tested the association between schizotypy traits in healthy subjects and mentalizing-related neural correlates to provide new insights into neural processes associated with subclinical schizophrenia traits.Methods: Brain activation was measured using fMRI during an interactive mentalizing paradigm (Prisoner's Dilemma Game) in 164 healthy subjects. The Schizotypal Personality Questionnaire (SPQ-B) was administered to assess the three dimensions of schizotypy, i.e., cognitive-perceptual, interpersonal and disorganized.Results: We found that interpersonal schizotypy was significantly negatively correlated with brain activation in bilateral precunei and right caudate nucleus (among others) during mentalizing. By contrast, disorganized schizotypy was significantly positively correlated with mentalizing-associated neural activation in right precuneus, left middle cingulate cortex and right cerebellar hemisphere. No significant associations for cognitive-perceptual schizotypy and the SPQ-B total score were found.Discussion: Our study showed that interpersonal and disorganized schizotypy are associated with neural correlates of mentalizing in brain regions that are involved in self-processing and mentalizing. These brain regions have also been linked to mentalizing in schizophrenia.</p

Cryptic persistence and loss of local endemism in Lake Constance charr subject to anthropogenic disturbance

In the welcome circumstance that species believed extinct are rediscovered, it is often the case that biological knowledge acquired before the presumed extinction is limited. Efforts to address these knowledge gaps, in particular to assess the taxonomic integrity and conservation status of such species, can be hampered by a lack of genetic data and scarcity of samples in museum collections. Here, we present a proof-of-concept case study based on a multidisciplinary data evaluation approach to tackle such problems. The approach was developed after the rediscovery, 40 years after its presumed extinction, of the enigmatic Lake Constance deep-water charr Salvelinus profundus. Targeted surveys led to the capture of further species and additional sympatric normal charr, Salvelinus cf. umbla. Since the lake had been subject to massive stocking in the past, an evaluation of the genetic integrity of both extant forms was called for in order to assess possible introgression. A two-step genomic approach was developed based on restriction site associated DNA (RAD). Diagnostic population genomic (single nucleotide polymorphism [SNP]) data were harvested from contemporary samples and used for RNA bait design to perform target capture in DNA libraries of archival scale material, enabling a comparison between extant and historic samples. Furthermore, life history traits and morphological data for both extant forms were gathered and compared with historical data from the past 60–120 years. While extant deep-water charr matched historical deep-water specimens in body shape, gill raker count, and growth rates, significant differences were discovered between historical and extant normal charr. These resulted were supported by genomic analyses of contemporary samples, revealing the two extant forms to be highly divergent. The results of population assignment tests suggest that the endemic deep-water charr persisted in Lake Constance during the eutrophic phase, but not one of the historical genomic samples could be assigned to the extant normal charr taxon. Stocking with non-endemic charr seems to be the most likely reason for these changes. This proof-of-concept study presents a multidisciplinary data evaluation approach that simultaneously tests population genomic integrity and addresses some of the conservation issues arising from rediscovery of a species characterized by limited data availability.publishedVersio

Dual RF Astrodynamic GPS Orbital Navigator Satellite

Dual RF Astrodynamic GPS Orbital Navigator Satellite (DRAGONSat) will demonstrate autonomous rendezvous and docking (ARD) in low Earth orbit (LEO) and gather flight data with a global positioning system (GPS) receiver strictly designed for space applications. ARD is the capability of two independent spacecraft to rendezvous in orbit and dock without crew intervention. DRAGONSat consists of two picosatellites (one built by the University of Texas and one built by Texas A and M University) and the Space Shuttle Payload Launcher (SSPL); this project will ultimately demonstrate ARD in LEO