Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of motor neurons and a mechanosensitive sensory neuron in the defecation circuitry of Drosophila larvae

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca2+ imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction. DOI: http://dx.doi. org/10.7554/eLife.03293. 001
Molecular basis of inherited epilepsy.

Epilepsy is a common, paroxysmal, and heterogeneous neurological disorder. Many factors, including complex genetic influences, contribute to the pathogenesis of epilepsy. However, several epilepsy syndromes are caused by mutations in single genes (Table). Most epilepsy-associated genes that have been identified within the past 5 years encode ion channels. This review illustrates the progress in defining the molecular basis of inherited epilepsies and highlights conditions caused by dysfunctional ion channels. Ion channels may be broadly classified as voltage or ligand gated, depending on whethertheprimarystimulusfortheiractivity is a change in local membrane potential or a chemical messenger (eg, neurotransmitter). The role of ion channels in neuronal excitability is well established, and the identification of mutationsinneuronalionchannelgeneslinked to inherited epilepsy emphasizes the delicate balances that maintain electrical harmonyinthecentralnervoussystem.These discoveries have also revealed new approaches to diagnosis and disease categorization, with the ultimate hope of new, gene-specific therapeutics.
Peer review under the microscope. An agent-based model of scientific collaboration

This paper investigates whether the quality and efficiency of peer review is more influenced by scientists' behaviour or by the type of scientific community structure (homogeneous vs. heterogeneous). We looked especially at the importance of reciprocity and fairness to ensure cooperation between everyone involved and the role of evaluation standards to reduce parochialism. We modelled peer review as a process based on knowledge asymmetries and subject to evaluation bias. We found that reciprocity can have a positive effect on peer review only when agents are not driven by self-interest motivation and are inspired by standards of fairness. Secondly, we found that in a strong competitive scientific landscape, high quality of peer review can be achieved when shared evaluation standards are supported by normative standards of conduct. Finally, we found that unequal resource allocation in science (e.g., reputation and funds) is the consequence of good peer review standards.
Continuous subcutaneous insulin infusion treatment in insulin-dependent diabetic patients: a comparison with conventional optimized treatment in a long-term study.

The effects of continuous subcutaneous insulin infusion (CSII) by portable pump (Microjet MC2, Miles) and conventional optimized insulin therapy (OCT) on metabolic control were compared in a group of five insulin-dependent diabetic patients. A group of seven normal volunteers was examined as control. CSII treatment consisted of a basal insulin infusion and three boluses of 60 min, starting 30 min before each main meal. OCT was characterized by three daily s.c. insulin injections: regular insulin before breakfast and lunch, regular plus lente before dinner. Two protocols of study were performed. In the first one the metabolic (blood glucose, NEFA, 3-beta-OH-butyrate) and hormonal (free insulin, pancreatic glucagon, cortisol, growth hormone) profiles were examined in the hospital with the patients connected to a "blood glucose monitor," after 45 days of OCT and CSII treatment, respectively. In the course of CSII treatment, a better blood glucose profile was observed than during OCT (OCT: MBG = 162 +/- 18 mg/dl, M = 43 +/- 11, MAGE = 151 +/- 26 mg/dl. CSII: MBG = 133 +/- 8 mg/dl, M = 29 +/- 5, MAGE = 138 +/- 19 mg/dl: P less than 0.05), although the indices remained higher than in normal subjects (MBG = 85 +/- 3 mg/dl, M = 0.98 +/- 0.18, MAGE = 49 +/- 3.6 mg/dl). CSII treatment was also associated with an improvement of NEFA and 3-beta-OH-butyrate profiles. Plasma "free" insulin (IRI) ranged between 18.2 +/- 5.4 and 32 +/- 5.5 microU/ml during CSII. Plasma glucagon (IRG) concentration after overnight fast was 195 +/- 65 pg/ml and 220 +/- 55 pg/ml during OCT and CSII treatment, respectively, with minor changes throughout the day. (ABSTRACT TRUNCATED AT 250 WORDS)
Fast orthogonal iteration adaptive algorithms for the generalized symmetric eigenproblem

A class of sequential orthogonal iteration updating algorithms for the time-varying generalized symmetric eigenproblem (GSE) is presented. These algorithms are maximally fast, requiring N/sup 2/+O(Nr) arithmetic operations each time step for tracking the r dominant eigenvectors and eigenvalues of an exponentially updated GSE of dimension N. Applications to subspace adaptive filtering and frequency estimation are also discussed. Detailed computer experiments lend empirical support to the theoretical findings.
Output-based event-triggered control with Guaranteed ℒ∞-gain and improved event-triggering

Most event-triggered controllers available nowadays are based on static state-feedback controllers. As in many control applications the full state is not available for feedback, it is the objective of this paper to propose event-triggered dynamical output-based controllers. The fact that the controller is based on output feedback instead of state feedback does not allow for straightforward extensions of existing event-triggering mechanisms if a minimum time between two subsequent events, the so-called ‘minimum inter-event time’, has to be guaranteed. Therefore, we will propose an event-triggering mechanism that invokes execution of the control task when the difference between the measured output or the control input of the plant or controller, respectively, and its previously sampled value becomes ‘large’ compared to its current value and an additional threshold. For such event-triggering mechanisms, we will study closed-loop stability and ℒ∞-performance and provide bounds on the minimum inter-event time. In addition, we will model the event-triggered control system using impulsive systems, which truly describe the behaviour of the event-triggered control system. As a result, we can guarantee stability and performance for improved event-triggered controllers with larger minimum inter-event times than existing results in literature.
The Economic Effects of Energy Price Shocks

Large fluctuations in energy prices have been a distinguishing characteristic of the U.S. economy since the 1970s. Turmoil in the Middle East, rising energy prices in the U.S. and evidence of global warming recently have reignited interest in the link between energy prices and economic performance. This paper addresses a number of the key issues in this debate: What are energy price shocks and where do they come from? How responsive is energy demand to changes in energy prices? How do consumers' expenditure patterns evolve in response to energy price shocks? How do energy price shocks affect real output, inflation, stock markets and the balance-of-payments? Why do energy price increases seem to cause recessions, but energy price decreases do not seem to cause expansions? Why has there been a surge in gasoline prices in recent years? Why has this new energy price shock not caused a recession so far? Have the effects of energy price shocks waned since the 1980s and, if so, why? As the paper demonstrates, it is critical to account for the endogeneity of energy prices and to differentiate between the effects of demand and supply shocks in energy markets, when answering these questions.
A class of hybrid collocation methods for third-order ordinary differential equations

A class of numerical methods is proposed for solving general third-order ordinary differential equations directly by collocation at the grid points x = x n+j , i = 0(1)k and at an off grid point x = x n+u , where k is the step number of the method and u is an arbitrary rational number in (x n , x n+k ). A predictor of order 2k − 1 is also proposed to cater for y n+k in the main method. Taylor series expansion is employed for the calculation of y n+1, y n+2, y n+u and their higher derivatives. Evaluation of the resulting method at x = x n+k for any value of u in the specified open interval yields a particular discrete scheme as a special case of the method. The efficiency of the method is tested on some general initial value problems of third-order ordinary differential equations.
Relation of plasma Obestatin levels with BMI and HOMA-IR in Syrian obese patients with type 2 diabetes

Methods: 23 normal weight subjects, 35 obese subjects and 31 obese patients with T2D participated in the study, the body mass index was calculated. Fasting glucose and insulin levels were measured and the homeostasis model assessment of insulin resistance (HOMAIR) was determined. Plasma obestatin levels were measured with enzyme-linked immune sorbent assay (ELISA). The relationship between plasma obestatin levels and biochemical parameters was also analyzed.
Internal dynamics of the radio halo cluster Abell 2744

Aims. We present a detailed dynamical analysis of the rich galaxy cluster A2744, containing a powerful diffuse radio halo. Methods. Our analysis is based on redshift data for 102 galaxies, part of them recovered from unexplored spectra in the ESO archive. We combine galaxy velocity and position information to select the cluster members and determine global dynamical properties of the cluster. We use a variety of statistical tests to detect possible substructures. Results. We find that A2744 appears as a well isolated peak in the redshift space at $\left =0.306$, which includes 85 galaxies recognized as cluster members. We compute the line-of-sight (LOS) velocity dispersion of galaxies, $\sigma_{\rm V}=1767_{-99}^{+121}$ km s -1 , which is significantly larger than what is expected in the case of a relaxed cluster with an observed X-ray temperature of 8 keV. We find evidence that this cluster is far from dynamical equilibrium, as shown by the non-Gaussian nature of the velocity distribution, the presence of a velocity gradient and a significant substructure. Our analysis shows the presence of two galaxy clumps of different mean LOS velocities $\Delta V \sim 4000$ km s -1 . We detect a main, low-velocity clump with $\sigma_{\rm V}\sim 1200{-}1300$ km s$^{-1} \;$and a secondary, high-velocity clump with $\sigma_{\rm V}= 500{-}800$ km s -1 and located in the S-SW cluster region. We estimate a cluster mass within 1 Mpc$\;$of $1.4{-}2.4\times 10^{15}~M_{\odot}$, depending on the model adopted to describe the cluster dynamics. Conclusions. Our results suggest a merging scenario of two clumps with a mass ratio of 3:1 and a LOS impact velocity of $\Delta V_{\rm rf} \sim 3000$ km s -1 , likely observed just after the core passage. The merging is occuring roughly in the NS direction with the axis close to the LOS. This scenario agrees with that proposed on the basis of recent Chandra results in its general lines although suggesting a somewhat more advanced merging phase. Our conclusions support the view of the connection between extended radio emission and energetic merging phenomena in galaxy clusters.
Water solubilization of glycated carp and scallop myosin rods, and their soluble state under physiological conditions

Myosin rod regions prepared from carp Cyprinus carpio dorsal muscle and scallop Pecten yessoensis striated adductor muscle were non-enzymatically reacted with glucose (glycation), and the changes in the filament-forming ability and the size distribution of the rod filaments during glycation were examined to discuss the molecular mechanism of the water solubilization of myosin molecules under physiological conditions. Both myosin rods became solubilized in 0.1 M NaCl (pH 7.5), and their filament-forming ability was weakened with the progress of glycation. The size of the insoluble filaments of the myosin rods was diminished with an increase in the solubility under physiological conditions, and glycated myosin rods finally existed as monomers in 0.1 M NaCl (pH 7.5). These results supported the hypothesis that the water solubilization of myosin by glycation was caused by the loss of the filament-forming ability of myosin molecules. Water solubilization seemed to occur through the same molecular mechanism regardless of the species, whereas the scallop myosin rods required a much larger number of lysine residues reacted with glucose to collapse the insoluble filaments, in contrast to the carp myosin rods.
Multiparametric MRI Characterization and Prediction in Autism Spectrum Disorder Using Graph Theory and Machine Learning

This study employed graph theory and machine learning analysis of multiparametric MRI data to improve characterization and prediction in autism spectrum disorders (ASD). Data from 127 children with ASD (13.5±6.0 years) and 153 age- and gender-matched typically developing children (14.5±5.7 years) were selected from the multi-center Functional Connectome Project. Regional gray matter volume and cortical thickness increased, whereas white matter volume decreased in ASD compared to controls. Small-world network analysis of quantitative MRI data demonstrated decreased global efficiency based on gray matter cortical thickness but not with functional connectivity MRI (fcMRI) or volumetry. An integrative model of 22 quantitative imaging features was used for classification and prediction of phenotypic features that included the autism diagnostic observation schedule, the revised autism diagnostic interview, and intelligence quotient scores. Among the 22 imaging features, four (caudate volume, caudate-cortical functional connectivity and inferior frontal gyrus functional connectivity) were found to be highly informative, markedly improving classification and prediction accuracy when compared with the single imaging features. This approach could potentially serve as a biomarker in prognosis, diagnosis, and monitoring disease progression.
Statistical Inference of Selection and Divergence of the Rice Blast Resistance Gene Pi-ta

The resistance gene Pi-ta has been effectively used to control rice blast disease, but some populations of cultivated and wild rice have evolved resistance. Insights into the evolutionary processes that led to this resistance during crop domestication may be inferred from the population history of domesticated and wild rice strains. In this study, we applied a recently developed statistical method, time-dependent Poisson random field model, to examine the evolution of the Pi-ta gene in cultivated and weedy rice. Our study suggests that the Pi-ta gene may have more recently introgressed into cultivated rice, indica and japonica, and U.S. weedy rice from the wild species, O. rufipogon. In addition, the Pi-ta gene is under positive selection in japonica, tropical japonica, U.S. cultivars and U.S. weedy rice. We also found that sequences of two domains of the Pi-ta gene, the nucleotide binding site and leucine-rich repeat domain, are highly conserved among all rice accessions examined. Our results provide a valuable analytical tool for understanding the evolution of disease resistance genes in crop plants.
Transcriptomic Changes Triggered by Hypoxia: Evidence for HIF-1α -Independent, [Na+]i/[K+]i-Mediated, Excitation-Transcription Coupling

This study examines the relative impact of canonical hypoxia-inducible factor-1alpha- (HIF-1α and Na+ i/K+ i-mediated signaling on transcriptomic changes evoked by hypoxia and glucose deprivation. Incubation of RASMC in ischemic conditions resulted in ∼3-fold elevation of [Na+]i and 2-fold reduction of [K+]i. Using global gene expression profiling we found that Na+,K+-ATPase inhibition by ouabain or K+-free medium in rat aortic vascular smooth muscle cells (RASMC) led to the differential expression of dozens of genes whose altered expression was previously detected in cells subjected to hypoxia and ischemia/reperfusion. For further investigations, we selected Cyp1a1, Fos, Atf3, Klf10, Ptgs2, Nr4a1, Per2 and Hes1, i.e. genes possessing the highest increments of expression under sustained Na+,K+-ATPase inhibition and whose implication in the pathogenesis of hypoxia was proved in previous studies. In ouabain-treated RASMC, low-Na+, high-K+ medium abolished amplification of the [Na+]i/[K+]i ratio as well as the increased expression of all tested genes. In cells subjected to hypoxia and glucose deprivation, dissipation of the transmembrane gradient of Na+ and K+ completely eliminated increment of Fos, Atf3, Ptgs2 and Per2 mRNAs and sharply diminished augmentation expression of Klf10, Edn1, Nr4a1 and Hes1. In contrast to low-Na+, high-K+ medium, RASMC transfection with Hif-1a siRNA attenuated increments of Vegfa, Edn1, Klf10 and Nr4a1 mRNAs triggered by hypoxia but did not impact Fos, Atf3, Ptgs2 and Per2 expression. Thus, our investigation demonstrates, for the first time, that Na+ i/K+ i-mediated, Hif-1α- -independent excitation-transcription coupling contributes to transcriptomic changes evoked in RASMC by hypoxia and glucose deprivation.
Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors

Significance Reversible and repetitive structural changes are essential for ligand-gated ion channels to mediate biological signaling. The inositol 1,4,5-trisphosphate receptor (IP3R) assembles ligand-gated ion channels that mediate calcium signaling. IP3 activates channels at a distance by reversible allosteric changes in the IP3R tetramer. Here we show a new mode of posttranslational modification that irreversibly blocks allosteric changes in the IP3R. We identified an IP3R-modifying enzyme as tissue transglutaminase that inhibits IP3R function by locking subunit configurations. This modification chronically impaired calcium signaling and autophagy regulation in living cells, and up-regulated modification was observed in Huntington disease models. To our knowledge, this is the first demonstration of transglutaminase-catalyzed posttranslational modification in ligand-gated channel allostery and provides a new framework for enzymatic regulation of allostery. The inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum mediates calcium signaling that impinges on intracellular processes. IP3Rs are allosteric proteins comprising four subunits that form an ion channel activated by binding of IP3 at a distance. Defective allostery in IP3R is considered crucial to cellular dysfunction, but the specific mechanism remains unknown. Here we demonstrate that a pleiotropic enzyme transglutaminase type 2 targets the allosteric coupling domain of IP3R type 1 (IP3R1) and negatively regulates IP3R1-mediated calcium signaling and autophagy by locking the subunit configurations. The control point of this regulation is the covalent posttranslational modification of the Gln2746 residue that transglutaminase type 2 tethers to the adjacent subunit. Modification of Gln2746 and IP3R1 function was observed in Huntington disease models, suggesting a pathological role of this modification in the neurodegenerative disease. Our study reveals that cellular signaling is regulated by a new mode of posttranslational modification that chronically and enzymatically blocks allosteric changes in the ligand-gated channels that relate to disease states.
Cold Transiently Activates Calcium-Permeable Channels in Arabidopsis Mesophyll Cells1[W]

Living organisms are capable of discriminating thermal stimuli from noxious cold to noxious heat. For more than 30 years, it has been known that plant cells respond to cold with a large and transient depolarization. Recently, using transgenic Arabidopsis (Arabidopsis thaliana) expressing the calcium-sensitive protein aequorin, an increase in cytosolic calcium following cold treatment was observed. Applying the patch-clamp technique to Arabidopsis mesophyll protoplasts, we could identify a transient plasma membrane conductance induced by rapid cooling. This cold-induced transient conductance was characterized as an outward rectifying 33 pS nonselective cation channel. The permeability ratio between calcium and cesium was 0.7, pointing to a permeation pore >3.34 Å (ø of cesium). Our experiments thus provide direct evidence for the predicted but not yet measured cold-activated calcium-permeable channel in plants.
Overexpression of Arabidopsis Molybdenum Cofactor Sulfurase Gene Confers Drought Tolerance in Maize (Zea mays L.)

Abscisic acid (ABA) is a key component of the signaling system that integrates plant adaptive responses to abiotic stress. Overexpression of Arabidopsis molybdenum cofactor sulfurase gene (LOS5) in maize markedly enhanced the expression of ZmAO and aldehyde oxidase (AO) activity, leading to ABA accumulation and increased drought tolerance. Transgenic maize (Zea mays L.) exhibited the expected reductions in stomatal aperture, which led to decreased water loss and maintenance of higher relative water content (RWC) and leaf water potential. Also, transgenic maize subjected to drought treatment exhibited lower leaf wilting, electrolyte leakage, malondialdehyde (MDA) and H2O2 content, and higher activities of antioxidative enzymes and proline content compared to wild-type (WT) maize. Moreover, overexpression of LOS5 enhanced the expression of stress-regulated genes such as Rad 17, NCED1, CAT1, and ZmP5CS1 under drought stress conditions, and increased root system development and biomass yield after re-watering. The increased drought tolerance in transgenic plants was associated with ABA accumulation via activated AO and expression of stress-related gene via ABA induction, which sequentially induced a set of favorable stress-related physiological and biochemical responses.
Molecular dynamics simulations highlight mobile regions in proteins: A novel suggestion for converting a murine V(H) domain into a more tractable species.

The V(H) region of the murine antibody 1F7 has been identified as a single-domain chorismate mutase, but a tendency to denature and aggregate has hampered its biochemical characterization. Standard mutagenesis approaches targeting antibody chain dimerization areas have been exhausted. We describe a new approach to the problem, where we use molecular dynamics (MD) simulations to find the differences between the untractable protein and the known soluble V(H) domain from a llama antibody. MD simulations of proteins yield information on the relative stability and fluctuations of parts of the proteins. By comparing simulation results of two related proteins their differences in stability and fluctuations can be analyzed and may suggest mutations aimed at (de)stabilization of one of the two proteins. For the mouse versus llama simulations, this approach highlights an untried area in the protein which shows increased fluctuations. The replacement of this eight-residue segment with the corresponding llama sequence gave a chimeric mutant which shows significantly decreased fluctuations. We see this as a general scheme to generate suggestions for mutagenesis experiments, not only obviously generalizable to other immunoglobulin domains, but to other protein systems as well.