Miracle-dz/UniFAR-FTUs huggingface dataset:
Aurone synthase is a catechol oxidase with hydroxylase activity and provides insights into the mechanism of plant polyphenol oxidases

Significance Catechol oxidases and tyrosinases belong to the family of polyphenol oxidases (PPOs). In contrast to tyrosinases, catechol oxidases were so far defined to lack hydroxylase activity toward monophenols. Aurone synthase (AUS1) is a plant catechol oxidase that specializes in the conversion of chalcones to aurones (flower pigments). We evidence for the first time, to our knowledge, hydroxylase activity for a catechol oxidase (AUS1) toward its natural monophenolic substrate (chalcone). The presented first crystal structure of a plant pro-PPO provides insights into its activation mechanisms, and based on biochemical and structural studies of AUS1, we propose a novel catalytic reaction mechanism for plant PPOs. The proven hydroxylase functionality of AUS1 suggests that other catechol oxidases might also be involved in the plant’s secondary metabolism. Tyrosinases and catechol oxidases belong to the family of polyphenol oxidases (PPOs). Tyrosinases catalyze the o-hydroxylation and oxidation of phenolic compounds, whereas catechol oxidases were so far defined to lack the hydroxylation activity and catalyze solely the oxidation of o-diphenolic compounds. Aurone synthase from Coreopsis grandiflora (AUS1) is a specialized plant PPO involved in the anabolic pathway of aurones. We present, to our knowledge, the first crystal structures of a latent plant PPO, its mature active and inactive form, caused by a sulfation of a copper binding histidine. Analysis of the latent proenzyme’s interface between the shielding C-terminal domain and the main core provides insights into its activation mechanisms. As AUS1 did not accept common tyrosinase substrates (tyrosine and tyramine), the enzyme is classified as a catechol oxidase. However, AUS1 showed hydroxylase activity toward its natural substrate (isoliquiritigenin), revealing that the hydroxylase activity is not correlated with the acceptance of common tyrosinase substrates. Therefore, we propose that the hydroxylase reaction is a general functionality of PPOs. Molecular dynamics simulations of docked substrate–enzyme complexes were performed, and a key residue was identified that influences the plant PPO’s acceptance or rejection of tyramine. Based on the evidenced hydroxylase activity and the interactions of specific residues with the substrates during the molecular dynamics simulations, a novel catalytic reaction mechanism for plant PPOs is proposed. The presented results strongly suggest that the physiological role of plant catechol oxidases were previously underestimated, as they might hydroxylate their—so far unknown—natural substrates in vivo.
Who Benefits from Teams? Comparing Workers, Supervisors, and Managers

This article offers a political explanation for the diffusion and sustainability of team-based work systems by examining the differential outcomes of team structures for 1200 workers, supervisors, and middle managers in a large unionized telecommunications company. Regression analyses show that participation in self-managed teams is associated with significantly higher levels of perceived discretion, employment security, and satisfaction for workers and the opposite for supervisors. Middle managers who initiate team innovations report higher employment security but otherwise are not significantly different from their counterparts who are not involved in innovations. By contrast, there are no significant outcomes for employees associated with their participation in off-line problem-solving teams.
Patient Burden of Trigeminal Neuralgia: Results from a Cross‐Sectional Survey of Health State Impairment and Treatment Patterns in Six European Countries

Abstract: Trigeminal neuralgia (TN) is an uncommon neuropathic condition associated with excruciating facial pain. It is important to determine the effect of TN pain on patient functioning and to characterize relevant pharmacologic treatment patterns and health resource utilization in general practice. Eighty‐two patients with TN were identified in a general practice setting during an observational survey of broad neuropathic pain syndromes in six European countries. Patients answered a questionnaire that included pain severity and interference items from the modified Short Form Brief Pain Inventory (mBPI‐SF), the EuroQol Survey of functioning and well‐being (EQ‐5D), and questions related to current treatment, health status, and resource utilization. Physicians provided information on medications prescribed for TN pain and pain‐related comorbidities (anxiety, depression, and sleep disturbance). The mean patient age was 62.7 ± 15.8 years, 46% were ≥65 years, and 66% of patients had TN >1 year of duration. The mean Pain Severity Index was 4.2 (range 0–10), reflecting moderate pain despite 94% of patients taking prescription medications for their TN pain. Prescription medications included carbamazepine (mean daily dose 534.1 ± 269.8 mg), the recommended first‐line pharmacologic therapy for TN. Pain severity was significantly associated with reduced EQ‐5D health state valuation (P < 0.001) and greater pain interference (mBPI‐SF) (P < 0.001). These findings demonstrate that TN pain presents a substantial patient burden expressed as interference with daily functioning and reduced health status associated with pain severity. This burden may result from both suboptimal management strategies and the frequent resistance of this neuropathic condition to treatment, and suggests a need for more effective pain management strategies.
Genetic interactions suggest that Danforth's short tail (Sd) is a gain-of-function mutation.

Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2 that acts cell autonomously in the notochord and leads to its distintegration, and thus causes severe defects in somite patterning and vertebral column development. The molecular nature of the Sd gene and mutation is unknown, and it is unclear whether Sd is a loss-of-function mutation and the semidominant inheritance of the Sd phenotype is due to haploinsufficiency, or whether Sd represents a gain-of-function mutation in a gene essential for notochord development and maintenance. Here, we report on the genetic interaction between Sd and an insertional mutation called Etl4lacZ, which provides genetic evidence that Sd is a gain-of-function mutation. Etl4lacZ is an enhancer trap insertion, which gives rise to lacZ expression in distinct cell types, including the notochord. In homozygosity, the lacZ insertion leads to abnormal vertebrae in the caudal part of the vertebral column. Etl4lacZ maps approximately 0.75 cM distal to Sd, and in double heterozy gotes modifies the Sd phenotype contrarily, depending on the chromosomal configuration of the Sd and Etl4lacZ mutations: when Etl4lacZ is present on the chromosome wild type for Sd (Sd+/+ Etl4lacZ; trans configuration), the Sd phenotype is enhanced, i.e., vertebral malformations extend to more anterior positions and the vertebral body of the axis is further reduced. Conversely, when Etl4lacZ is present on the same chromosome as Sd (Sd Etl4lacZ/+ +; cis configuration), the Sd phenotype is attenuated, i.e., vertebral malformations are confined to more posterior levels, and the dens axis, which is severely reduced or absent in Sd heterozygotes, is restored. The different effect of the Etl4lacZ insertion on Sd, depending on its presence in trans or cis, suggests a direct interaction of the transgene insertion with the Sd gene. Additionally, the attenuation of the Sd phenotype by Etl4lacZ in cis suggests that Sd is a gain-of-function mutation and lends support to the idea that Etl4lacZ is a new allele of Sd. Dev. Genet. 23:86-96, 1998.
Strategies for Achieving High Sequencing Accuracy for Low Diversity Samples and Avoiding Sample Bleeding Using Illumina Platform

Sequencing microRNA, reduced representation sequencing, Hi-C technology and any method requiring the use of in-house barcodes result in sequencing libraries with low initial sequence diversity. Sequencing such data on the Illumina platform typically produces low quality data due to the limitations of the Illumina cluster calling algorithm. Moreover, even in the case of diverse samples, these limitations are causing substantial inaccuracies in multiplexed sample assignment (sample bleeding). Such inaccuracies are unacceptable in clinical applications, and in some other fields (e.g. detection of rare variants). Here, we discuss how both problems with quality of low-diversity samples and sample bleeding are caused by incorrect detection of clusters on the flowcell during initial sequencing cycles. We propose simple software modifications (Long Template Protocol) that overcome this problem. We present experimental results showing that our Long Template Protocol remarkably increases data quality for low diversity samples, as compared with the standard analysis protocol; it also substantially reduces sample bleeding for all samples. For comprehensiveness, we also discuss and compare experimental results from alternative approaches to sequencing low diversity samples. First, we discuss how the low diversity problem, if caused by barcodes, can be avoided altogether at the barcode design stage. Second and third, we present modified guidelines, which are more stringent than the manufacturer’s, for mixing low diversity samples with diverse samples and lowering cluster density, which in our experience consistently produces high quality data from low diversity samples. Fourth and fifth, we present rescue strategies that can be applied when sequencing results in low quality data and when there is no more biological material available. In such cases, we propose that the flowcell be re-hybridized and sequenced again using our Long Template Protocol. Alternatively, we discuss how analysis can be repeated from saved sequencing images using the Long Template Protocol to increase accuracy.
The Apache Point Observatory Lunar Laser-ranging Operation: Instrument Description and First Detections

A next-generation lunar laser-ranging apparatus using the 3.5 m telescope at the Apache Point Observatory in southern New Mexico has begun science operation. The Apache Point Observatory Lunar Laser-ranging Operation (APOLLO) has achieved 1 mm range precision to the moon, which should lead to approximately 1 order-of-magnitude improvements in several tests of fundamental properties of gravity. We briefly outline the scientific goals, and then give a detailed discussion of the APOLLO instrumentation.
Introducing BigMag — A novel system for 3D magnetic actuation of flexible surgical manipulators

Magnetic interaction can be utilized for remote actuation of surgical manipulators. However, platforms currently available for that purpose have limited workspaces, inadequate field strength or very low bandwidth of the electrical subsystem. In this paper, we present BigMag, a novel platform capable of magnetic steering of continuum manipulators for medical purposes. BigMag comprises of 6 mobile coils and is capable of generating the fields of at least 40 mT in any direction at every point of its workspace. Moreover, we introduce a mathematical model for 3D mobile coil arrays. Each coil is modelled using finite element data adjusted by measurement-based correction, (a maximum observed mean error between the model and the prediction of 3.36 ± 5.62%). The model for a full system is validated in two tasks. In the first task, the system executes a prescribed rotating field (mean error between the model and measurement of 7.51% and minimum R2 of 0.964). The second task tests the estimation of the field for known 3D trajectories (minimum R2 of 0.967). The investigation concludes with a demonstration of BigMag capabilities in actuation of magnetic catheters in confined spaces usinguser-controlled steering.
Modeling and optimization of high-power Nd3+-Yb3+codoped fiber lasers

High-power continuous-wave Nd 3+ -Yb 3+ codoped fiber lasers (NYDFL) are analyzed, based on a rate-propagation equations model. The model takes into account energy transfer between Nd 3+ and Yb 3+ , as well as cross relaxation between Nd 3+ ions, and contributions from high-order modes to the amplified spontaneous emission (ASE). Examples of cladding-pumped NYDFLs with distributed Bragg reflector (DBR) at either end are presented. We demonstrate the optimal laser design by considering the effects of the Nd 3+ and Yb 3+ concentrations, pump wavelengths multiplexing, output mirror reflectivity, and the laser wavelength. Approximate quasi-analytical solutions are shown to be in good agreement with the exact numerical solutions of the rate equations for practical conditions.
Post-chikungunya chronic arthritis--our experience with DMARDs over two year follow up.

AIM 1) To study clinical features and laboratory findings in patients of post chikungunya chronic arthritis (PCCA). 2) To study effectivity of disease modifying antirheumatic drugs (DMARDs) in treatment of post-chikungunya chronic arthritis. MATERIALS AND METHODS Sixteen Chikungunya IgM positive patients having arthritis lasting more than 3 months in spite of NSAIDs and Hydroxychloroquine therapy were selected. Their clinical, laboratory and radiological features were noted. Disease activity was assessed by clinical parameters and Disease Activity Score System (DAS 28). Functional status was assessed by HAQ Questionnaire on follow-up visits over next 2 years. Effectivity of treatment with Sulfasalazine and Methotrexate was assessed. RESULTS Chronic inflammatory polyarthritis does occur following chikungunya infection. It involves large and small joints of hands and feet and is erosive and deforming. It is rheumatoid factor negative. AntiCCP antibody was positive in majority. Synovial biopsy revealed nongranulomatous chronic synovitis with infiltration with lymphocytes and plasma cells. It was negative for chikungunya RNA. Treatment with Sulfasalazine with and without methotrexate produced good response in 71.4 % and 12.5% respectively. CONCLUSIONS Chronic inflammatory, erosive and rarely deforming polyarthritis does occur after acute chikungunya infection in some (5.6%). It is seronegative and AntiCCP positive in majority. DMARDs like sulfasalazine and methotrexate are required and effective in treatment of PCCA.
In Vivo and In Vitro Anaerobic Mating in Candida albicans

ABSTRACT Candida albicans cells of opposite mating types are thought to conjugate during infection in mammalian hosts, but paradoxically, the mating-competent opaque state is not stable at mammalian body temperatures. We found that anaerobic conditions stabilize the opaque state at 37°C, block production of farnesol, and permit in vitro mating at 37°C at efficiencies of up to 84%. Aerobically, farnesol prevents mating because it kills the opaque cells necessary for mating, and as a corollary, farnesol production is turned off in opaque cells. These in vitro observations suggest that naturally anaerobic sites, such as the efficiently colonized gastrointestinal (GI) tract, could serve as niches for C. albicans mating. In a direct test of mating in the mouse GI tract, prototrophic cells were obtained from auxotrophic parent cells, confirming that mating will occur in this organ. These cells were true mating products because they were tetraploid, mononuclear, and prototrophic, and they contained the heterologous hisG marker from one of the parental strains.
Examining the neural basis of decision-making using social stimuli, dopamine and oxytocin in schizophrenia

2 BRIEF TABLE OF CONTENTS . 4 DETAILED TABLE OF CONTENTS . 5 LIST OF FIGURES . 9 LIST OF TABLES . 11 ACKNOWLEDGEMENTS . 12 CHAPTER 1 INTRODUCTION . 13 CHAPTER 2 METHODS AND MATERIALS . 35 CHAPTER 3 THE NEURAL CORRELATES OF DECISION-MAKING DURING AN ASSOCIATIVE LEARNING TASK WITH A SOCIAL COMPONENT – THE EFFECTS OF DOPAMINERGIC MANIPULATION IN HEALTHY PARTICIPANTS . 56 CHAPTER 4 THE NEURAL CORRELATES OF DECISION-MAKING DURING AN ASSOCIATIVE LEARNING TASK WITH A SOCIAL COMPONENT – IN PATIENTS WITH SCHIZOPHRENIA . 103 CHAPTER 5 NEUROPYHSIOLOGICAL EFFECTS OF ACUTE OXYTOCIN ADMINISTRATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PLACEBOCONTROLLED IMAGING STUDIES . 146 CHAPTER 6 THE NEURAL CORRELATES OF DECISION-MAKING DURING AN ASSOCIATIVE LEARNING TASK WITH A SOCIAL COMPONENT THE EFFECTS OF OXYTOCIN ADMINISTRATION IN PATIENTS WITH SCHIZOPHRENIA . 197 CHAPTER 7 GENERAL DISCUSSION . 241 REFERENCES . 254
Querying Incomplete Information in Semistructured Data

Semistructured data occur in situations where information lacks a homogeneous structure and is incomplete. Yet, up to now the incompleteness of information has not been reflected by special features of query languages. Our goal is to investigate the principles of queries that allow for incomplete answers. We do not present, however, a concrete query language. Queries over classical structured data models contain a number of variables and constraints on these variables. An answer is a binding of the variables by elements of the database such that the constraints are satisfied. In the present paper, we loosen this concept in so far as we allow also answers that are partial; that is, not all variables in the query are bound by such an answer. Partial answers make it necessary to refine the model of query evaluation. The first modification relates to the satisfaction of constraints: in some circumstances we consider constraints involving unbound variables as satisfied. Second, in order to prevent a proliferation of answers, we only accept answers that are maximal in the sense that there are no assignments that bind more variables and satisfy the constraints of the query. Our model of query evaluation consists of two phases, a search phase and a filter phase. Semistructured databases are essentially labeled directed graphs. In the search phase, we use a query graph containing variables to match a maximal portion of the database graph. We investigate three different semantics for query graphs, which give rise to three variants of matching. For each variant, we provide algorithms and complexity results. In the filter phase, the maximal matchings resulting from the search phase are subjected to constraints, which may be weak or strong. Strong constraints require all their variables to be bound, while weak constraints do not. We describe a polynomial algorithm for evaluating a special type of queries with filter constraints, and assess the complexity of evaluating other queries for several kinds of constraints. In the final part, we investigate the containment problem for queries consisting only of search constraints under the different semantics.
Social hierarchy in local Spanish-language print media: The discursive representation of Latino social actors in the United States

This study critically examines the discursive construction of social hierarchy in local Spanish-language print media with the goal of determining the extent to which these representations challenge those found in the mainstream media. It focuses on the ways in which four linguistic and two sociosemantic constructs represent Latino social actors in local Spanish-language print media. It finds two patterns in the representation of Latino social actors, each of which leads to the establishment of a particular social hierarchy. The first pattern reifies a traditional Us/Them hierarchy by representing Latinos as subordinate social actors to Anglo Americans. The second pattern represents Latinos as equal or dominant to Anglo Americans and thus levels or reverses the traditional Us/Them hierarchy. The latter pattern is indicative of the potential for local Spanish-language print media to challenge the putative subordinate position of Latinos in the United States.
Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue.
Retrograde endocannabinoid regulation of GABAergic inhibition in the rat dentate gyrus granule cell

The dentate gyrus is a key input gateway for the hippocampus, and dentate function is potently regulated by GABAergic inhibition. GABAergic inhibition is plastic and modulated by many factors. Cytoplasmic calcium ([Ca+]i) is one of these factors, and its elevation inhibits GABA‐mediated transmission in the hippocampus including the dentate gyrus granule cells (DGCs). We examined whether the [Ca+]i‐dependent decrease of GABAA receptor‐mediated inhibitory postsynaptic current (IPSC) is explained by the retrograde suppression of GABA release caused by the depolarization‐induced elevation of [Ca+]i in DGCs (DSI: depolarization‐induced suppression of inhibition). Repeated brief depolarizations or a single long depolarization inhibited spontaneous IPSCs with amplitudes over 25 pA for up to a minute, and reduced the amplitude of IPSCs evoked by direct stimulation in the molecular layer, suggesting that DGCs are susceptible to DSI. The magnitude of DSI correlated linearly with the duration of depolarization, and so did the increase of [Ca+]i. DSI was blocked by intrapipette application of BAPTA. In addition, bath application of thapsigargin and ryanodine, and intrapipette application of ryanodine and ruthenium red reduced the [Ca+]i increase caused by the DSI‐inducing depolarization, and substantially reduced the magnitude of DSI. Finally, the cannabinoid receptor agonists, CP55,942 and WIN55,212‐2, mimicked DSI and prevented further IPSC reduction by DSI. DSI was blocked by the antagonist, SR141716A. We conclude that GABAergic inhibition in DGCs is subject to endogenous cannabinoid (eCB)‐mediated retrograde regulation, and this process involves a depolarization‐initiated release of Ca+ from ryanodine‐sensitive stores. Our findings suggest eCBs probably have physiological functions in the regulation of GABAergic plasticity in the dentate gyrus.
Interaction between Lactic Acid Bacteria and Mycobacterium bovis in Ethiopian Fermented Milk: Insight into the Fate of M. bovis

ABSTRACT Mycobacterium bovis causes tuberculosis in animals and humans. Infected cows can transmit the bacillus to humans via milk. Milk also contains lactic acid bacteria (LAB). LAB isolated from milk were put in milk cultures together with spiked M. bovis. Different LAB had different abilities to reduce M. bovis counts, as M. bovis was undetectable in some while it persisted in two of the cultures.