171 research outputs found

    P143 Articular cartilage repair using in situ polymerizable hydrogel implant in osteochondral defects

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    Oops, our earnings were indeed preliminary: Market reactions to companies that subsequently file different earnings with the SEC

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    Abstract This study examines market reactions to earnings surprises in those special cases where firms revise earnings in their SEC filings from those reported just a few weeks earlier in the preliminary earnings announcements. We find that investors react to the new surprise in earnings upon the SEC filings in contrast to most of the prior literature which was unable to document market reactions to information in the SEC filings. Thus, our findings provide evidence that when the SEC filings contain material new information, investors incorporate it in pricing the firms' shares. We also find that market reactions are stronger for cases of downward earnings revisions than upward earnings revisions, but that an inverse drift in abnormal returns occurs for upward earnings revisions beyond the SEC filing date. Finally, we document that security analysts revise their forecasts upon the preliminary earnings announcement, but ignore the new information contained in the SEC filings

    The psychophysics of uneconomical choice: non-linear reward evaluation by a nectar feeder

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    Uneconomical choices by humans or animals that evaluate reward options challenge the expectation that decision-makers always maximize the return currency. One possible explanation for such deviations from optimality is that the ability to sense differences in physical value between available alternatives is constrained by the sensory and cognitive processes for encoding profitability. In this study, we investigated the capacity of a nectarivorous bat species (Glossophaga commissarisi) to discriminate between sugar solutions with different concentrations. We conducted a two-alternative free-choice experiment on a population of wild electronically tagged bats foraging at an array of computer-automated artificial flowers that recorded individual choices. We used a Bayesian approach to fit individual psychometric functions, relating the strength of preferring the higher concentration option to the intensity of the presented stimulus. Psychometric analysis revealed that discrimination ability increases non-linearly with respect to intensity. We combined this result with a previous psychometric analysis of volume perception. Our theoretical analysis of choice for rewards that vary in two quality dimensions revealed regions of parameter combinations where uneconomic choice is expected. Discrimination ability may be constrained by non-linear perceptual and cognitive encoding processes that result in uneconomical choice

    Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro

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    Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuromodulatory effect has been suggested to rest on acetylcholine receptor (AChR) activation on tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was shown involve adrenergic, splenic, pathways. Here we provide evidence that the adrenergic, rather than cholinergic, receptor activation on bone marrow derived DCs results in enhanced endocytosis uptake, enhanced IL-10 production but a decreased IL-6, IL-12p70 and IL-23 production. In antigen specific T cell stimulation assays, adrenergic β2 receptor activation on bone marrow DCs led to an enhanced potential to induce Foxp3 positive suppressive Treg cells. These effects were independent of IL10-R activation, TGFβ release, or retinoic acid (RA) secretion. Hence, adrenergic receptor β2 activation modulates DC function resulting in skewing towards anti-inflammatory T cell phenotypes

    MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

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    Erratum: https://link.springer.com/article/10.1007/s10863-014-9597-1MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.Funding support from Medical Research Council, United Kingdom; National Institutes of Health, United States; British Heart Foundation, United Kingdo

    Visual Analytics of Surveillance Data on Foodborne Vibriosis, United States, 1973–2010

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    Foodborne illnesses caused by microbial and chemical contaminants in food are a substantial health burden worldwide. In 2007, human vibriosis (non-cholera Vibrio infections) became a notifiable disease in the United States. In addition, Vibrio species are among the 31 major known pathogens transmitted through food in the United States. Diverse surveillance systems for foodborne pathogens also track outbreaks, illnesses, hospitalization and deaths due to non-cholera vibrios. Considering the recognition of vibriosis as a notifiable disease in the United States and the availability of diverse surveillance systems, there is a need for the development of easily deployed visualization and analysis approaches that can combine diverse data sources in an interactive manner. Current efforts to address this need are still limited. Visual analytics is an iterative process conducted via visual interfaces that involves collecting information, data preprocessing, knowledge representation, interaction, and decision making. We have utilized public domain outbreak and surveillance data sources covering 1973 to 2010, as well as visual analytics software to demonstrate integrated and interactive visualizations of data on foodborne outbreaks and surveillance of Vibrio species. Through the data visualization, we were able to identify unique patterns and/or novel relationships within and across datasets regarding (i) causative agent; (ii) foodborne outbreaks and illness per state; (iii) location of infection; (iv) vehicle (food) of infection; (v) anatomical site of isolation of Vibrio species; (vi) patients and complications of vibriosis; (vii) incidence of laboratory-confirmed vibriosis and V. parahaemolyticus outbreaks. The additional use of emerging visual analytics approaches for interaction with data on vibriosis, including non-foodborne related disease, can guide disease control and prevention as well as ongoing outbreak investigations

    Regulation of proteasome assembly and activity in health and disease

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    A Deubiquitylating Complex Required for Neosynthesis of a Yeast Mitochondrial ATP Synthase Subunit

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    The ubiquitin system is known to be involved in maintaining the integrity of mitochondria, but little is known about the role of deubiquitylating (DUB) enzymes in such functions. Budding yeast cells deleted for UBP13 and its close homolog UBP9 displayed a high incidence of petite colonies and slow respiratory growth at 37°C. Both Ubp9 and Ubp13 interacted directly with Duf1 (DUB-associated factor 1), a WD40 motif-containing protein. Duf1 activates the DUB activity of recombinant Ubp9 and Ubp13 in vitro and deletion of DUF1 resulted in the same respiratory phenotype as the deletion of both UBP9 and UBP13. We show that the mitochondrial defects of these mutants resulted from a strong decrease at 37°C in the de novo biosynthesis of Atp9, a membrane-bound component of ATP synthase encoded by mitochondrial DNA. The defect appears at the level of ATP9 mRNA translation, while its maturation remained unchanged in the mutants. This study describes a new role of the ubiquitin system in mitochondrial biogenesis

    Redundancy and the Evolution of Cis-Regulatory Element Multiplicity

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    The promoter regions of many genes contain multiple binding sites for the same transcription factor (TF). One possibility is that this multiplicity evolved through transitional forms showing redundant cis-regulation. To evaluate this hypothesis, we must disentangle the relative contributions of different evolutionary mechanisms to the evolution of binding site multiplicity. Here, we attempt to do this using a model of binding site evolution. Our model considers binding sequences and their interactions with TFs explicitly, and allows us to cast the evolution of gene networks into a neutral network framework. We then test some of the model's predictions using data from yeast. Analysis of the model suggested three candidate nonadaptive processes favoring the evolution of cis-regulatory element redundancy and multiplicity: neutral evolution in long promoters, recombination and TF promiscuity. We find that recombination rate is positively associated with binding site multiplicity in yeast. Our model also indicated that weak direct selection for multiplicity (partial redundancy) can play a major role in organisms with large populations. Our data suggest that selection for changes in gene expression level may have contributed to the evolution of multiple binding sites in yeast. We conclude that the evolution of cis-regulatory element redundancy and multiplicity is impacted by many aspects of the biology of an organism: both adaptive and nonadaptive processes, both changes in cis to binding sites and in trans to the TFs that interact with them, both the functional setting of the promoter and the population genetic context of the individuals carrying them

    Diversity in the Architecture of ATLs, a Family of Plant Ubiquitin-Ligases, Leads to Recognition and Targeting of Substrates in Different Cellular Environments

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    Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS) that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20–28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress
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