julilili42/papers huggingface dataset:
Extracellular Cyclophilin A Activates Platelets Via EMMPRIN (CD147) and PI3K/Akt Signaling, Which Promotes Platelet Adhesion and Thrombus Formation In Vitro and In Vivo
2014-12-31

Objective— Cyclophilin A (CyPA) is secreted under inflammatory conditions by various cell types. Whereas the important role of intracellular CyPA for platelet function has been reported, the effect of extracellular CyPA on platelet function has not been investigated yet. Approach and Results— Inhibition of extracellular CyPA through a novel specific inhibitor MM284 reduced thrombus after ferric chloride–induced injury in vivo. In vitro extracellular CyPA enhanced thrombus formation even in CyPA −/− platelets. Treatment of isolated platelets with recombinant CyPA resulted in platelet degranulation in a time- and dose-dependent manner. Inhibition of the platelet surface receptor extracellular matrix metalloproteinase inducer (cluster of differentiation 147) by an anticluster of differentiation 147 monoclonal antibody significantly reduced CyPA-dependent platelet degranulation. Pretreatment of platelets with CyPA enhanced their recruitment to mouse carotid arteries after arterial injury, which could be inhibited by an anticluster of differentiation 147 monoclonal antibody (intravital microscopy). The role of extracellular CyPA in adhesion could be confirmed by infusing CyPA −/− platelets in CyPA +/+ mice and by infusing CyPA +/+ platelets in CyPA −/− mice. Stimulation of platelets with CyPA induced phosphorylation of Akt, which could in turn be inhibited in the presence of phosphoinositid-3-kinase inhibitors. Akt-1 −/− platelets revealed a markedly decreased degranulation on CyPA stimulation. Finally, ADP-induced platelet aggregation was attenuated by MM284, as well as by inhibiting paracrine-secreted CyPA without directly affecting Ca 2+ -signaling. Conclusions— Extracellular CyPA activates platelets via cluster of differentiation 147–mediated phosphoinositid-3-kinase/Akt-signaling, leading to enhanced adhesion and thrombus formation independently of intracellular CyPA. Targeting extracellular CyPA via a specific inhibitor may be a promising strategy for platelet inhibition without affecting critical functions of intracellular CyPA.
The Bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl‐CoA carboxylase
2014-12-31

Summary Biosynthesis of fatty acids is one of the most fundamental biochemical pathways in nature. In bacteria and plant chloroplasts, the committed and rate‐limiting step in fatty acid biosynthesis is catalyzed by a multi‐subunit form of the acetyl‐ CoA carboxylase enzyme ( ACC ). This enzyme carboxylates acetyl‐ CoA to produce malonyl‐ CoA , which in turn acts as the building block for fatty acid elongation. In E scherichia coli , ACC is comprised of three functional modules: the biotin carboxylase ( BC ), the biotin carboxyl carrier protein ( BCCP ) and the carboxyl transferase ( CT ). Previous data showed that both bacterial and plant BCCP interact with signal transduction proteins belonging to the P II family. Here we show that the GlnB paralogues of the P II proteins from E . coli and A zospirillum brasiliense , but not the GlnK paralogues, can specifically form a ternary complex with the BC‐BCCP components of ACC . This interaction results in ACC inhibition by decreasing the enzyme turnover number. Both the BC‐BCCP ‐ GlnB interaction and ACC inhibition were relieved by 2‐oxoglutarate and by GlnB uridylylation. We propose that the GlnB protein acts as a 2‐oxoglutarate‐sensitive dissociable regulatory subunit of ACC in Bacteria.
Readability assessment for text simplification
2014-12-31

Readability assessment can play a role in the evaluation of a simplification algorithm as well as in the identification of what to simplify. While some previous research used traditional readability formulas to evaluate text simplification, there is little research into the utility of readability assessment for identifying and analyzing sentence level targets for text simplification. We explore this aspect in our paper by first constructing a readability model that is generalizable across corpora and across genres and later adapting this model to make sentence-level readability judgments. First, we report on experiments establishing that the readability model integrating a broad range of linguistic features works well at a document level, performing on par with the best systems on a standard test corpus. Next, the model is confirmed to be transferable to different text genres. Moving from documents to sentences, we investigate the model’s ability to correctly identify the difference in reading level between a sentence and its human simplified version. We conclude that readability models can be useful for identifying simplification targets for human writers and for evaluating machine generated simplifications.
Measurement of Compton Scattering from the Deuteron and an Improved Extraction of the Neutron Electromagnetic Polarizabilities
2014-12-31

The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data-and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here, we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world data set. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using chiral effective field theory with dynamical Δ(1232) degrees of freedom shows the data are consistent with and within the world data set. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities, and combining them with a recent result for the proton, we obtain the neutron polarizabilities as αn=[11.55±1.25(stat)±0.2(BSR)±0.8(th)]×10(-4) fm(3) and βn=[3.65∓1.25(stat)±0.2(BSR)∓0.8(th)]×10(-4) fm(3), with χ(2)=45.2 for 44 degrees of freedom.
N-gram probability effects in a cloze task
2014-12-31

What knowledge influences our choice of words when we write or speak? Predicting which word a person will produce next is not easy, even when the linguistic context is known. One task that has been used to assess context dependent word choice is the fill-in-the-blank task, also called the cloze task. The cloze probability of specific context is an empirical measure found by asking many people to fill in the blank. In this paper we harness the power of large corpora to look at the influence of corpus-derived probabilistic information from a word’s micro-context on word choice. We asked young adults to complete short phrases called n-grams with up to 20 responses per phrase. The probability of the responded word and the conditional probability of the response given the context were predictive of the frequency with which each response was produced. Furthermore the order in which the participants generated multiple completions of the same context was predicted by the conditional probability as well. These results suggest that word choice in cloze tasks taps into implicit knowledge of a person’s past experience with that word in various contexts. Furthermore, the importance of n-gram conditional probabilities in our analysis is further evidence of implicit knowledge about multi-word sequences and support theories of language processing that involve anticipating or predicting based on context.
Developmental control ofCFTR: from bioinformatics to novel therapeutic approaches
2014-12-31

Celebrating the 25th anniversary of identifying the genetic cause of cystic fibrosis (CF), tremendous progress has been made in the understanding and the treatment of this complex, but still fatal disease [1]. Despite advances, several key questions about the pathomechanisms of CF remain poorly understood. For instance, the precise genetic and epigenetic mechanisms that regulate expression and stability of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene remain incompletely defined. miRNA-binding blocker oligonucleotides offer an appealing option for developing tools to correct CFTR function <http://ow.ly/AjS8a>
Encouraging Family and Parent Education: Program Development and Evaluation in the Federal State of Baden-Württemberg, Germany
2014-12-31

Against the background of a European-wide strategy of governance aimed at improving support for parents and families, the following report details the conceptualization and evaluation of a federal state program4 in Baden-Württemberg (Germany) which was launched in 2008 to encourage family and parent education. Two program components, a voucher systemfor parents with a new-born child and an element that emphasizes educational offers for families with special needs in particular living situations, were started to increase requests for educational courses. The aim was to establish and deepen cooperation between different public and private professional services that are in contact with parents and their children.The results show that main goals of the program were reached.
An index-based framework for assessing patterns and trends in river fragmentation and flow regulation by global dams at multiple scales
2015-01-01

The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930–2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium sized dams and for the need to include waterfalls to establish a baseline of natural fragmentation. Our versatile framework can serve as a component of river fragmentation and connectivity assessments; as a standardized, easily replicable monitoring framework at global and basin scales; and as part of regional dam planning and management strategies.
Light-Activated Phytochrome A and B Interact with Members of the SPA Family to Promote Photomorphogenesis in Arabidopsis by Reorganizing the COP1/SPA Complex
2015-01-01

Phytochromes function as red/far-red photoreceptors in plants and are essential for light-regulated growth and development. Photomorphogenesis, the developmental program in light, is the default program in seed plants. In dark-grown seedlings, photomorphogenic growth is suppressed by the action of the CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1)/SUPPRESSOR OF phyA-105 (SPA) complex, which targets positive regulators of photomorphogenic growth for degradation by the proteasome. Phytochromes inhibit the COP1/SPA complex, leading to the accumulation of transcription factors promoting photomorphogenesis; yet, the mechanism by which they inactivate COP1/SPA is still unknown. Here, we show that light-activated phytochrome A (phyA) and phytochrome B (phyB) interact with SPA1 and other SPA proteins. Fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy analyses show that SPAs and phytochromes colocalize and interact in nuclear bodies. Furthermore, light-activated phyA and phyB disrupt the interaction between COP1 and SPAs, resulting in reorganization of the COP1/SPA complex in planta. The light-induced stabilization of HFR1, a photomorphogenic factor targeted for degradation by COP1/SPA, correlates temporally with the accumulation of phyA in the nucleus and localization of phyA to nuclear bodies. Overall, these data provide a molecular mechanism for the inactivation of the COP1/SPA complex by phyA- and phyB-mediated light perception.
Effects of Surgical and Dietary Weight Loss Therapy for Obesity on Gut Microbiota Composition and Nutrient Absorption
2015-01-01

Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>5</mml:mn></mml:math>per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525 .
WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome
2015-01-01

Autophagy is a pivotal cytoprotective process that secures cellular homeostasis, fulfills essential roles in development, immunity and defence against pathogens, and determines the lifespan of eukaryotic organisms. However, autophagy also crucially contributes to the development of age-related human pathologies, including cancer and neurodegeneration. Macroautophagy (hereafter referred to as autophagy) clears the cytoplasm by stochastic or specific cargo recognition and destruction, and is initiated and executed by autophagy related (ATG) proteins functioning in dynamical hierarchies to form autophagosomes. Autophagosomes sequester cytoplasmic cargo material, including proteins, lipids and organelles, and acquire acidic hydrolases from the lysosomal compartment for cargo degradation. Prerequisite and essential for autophagosome formation is the production of phosphatidylinositol 3-phosphate (PtdIns3P) by phosphatidylinositol 3-kinase class III (PI3KC3, also known as PIK3C3) in complex with beclin 1, p150 (also known as PIK3R4; Vps15 in yeast) and ATG14L. Members of the human WD-repeat protein interacting with phosphoinositides (WIPI) family play an important role in recognizing and decoding the PtdIns3P signal at the nascent autophagosome, and hence function as autophagy-specific PtdIns3P-binding effectors, similar to their ancestral yeast Atg18 homolog. The PtdIns3P effector function of human WIPI proteins appears to be compromised in cancer and neurodegeneration, and WIPI genes and proteins might present novel targets for rational therapies. Here, we summarize the current knowledge on the roles of the four human WIPI proteins, WIPI1–4, in autophagy. This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: ‘ERES: sites for autophagosome biogenesis and maturation?’ by Jana Sanchez-Wandelmer et al. (J. Cell Sci. 128, 185-192) and ‘Membrane dynamics in autophagosome biogenesis’ by Sven R. Carlsson and Anne Simonsen (J. Cell Sci. 128, 193-205).
Culture shapes whether the pursuit of happiness predicts higher or lower well-being.
2015-01-01

Pursuing happiness can paradoxically impair well-being. Here, the authors propose the potential downsides to pursuing happiness may be specific to individualistic cultures. In collectivistic (vs. individualistic) cultures, pursuing happiness may be more successful because happiness is viewed--and thus pursued--in relatively socially engaged ways. In 4 geographical regions that vary in level of collectivism (United States, Germany, Russia, East Asia), we assessed participants' well-being, motivation to pursue happiness, and to what extent they pursued happiness in socially engaged ways. Motivation to pursue happiness predicted lower well-being in the United States, did not predict well-being in Germany, and predicted higher well-being in Russia and in East Asia. These cultural differences in the link between motivation to pursue happiness and well-being were explained by cultural differences in the socially engaged pursuit of happiness. These findings suggest that culture shapes whether the pursuit of happiness is linked with better or worse well-being, perhaps via how people pursue happiness.
Distinct Functions of Neutrophil in Cancer and Its Regulation
2015-01-01

Neutrophils are the most abundant of all white blood cells in the human circulation and are usually associated with inflammation and with fighting infections. In recent years the role immune cells play in cancer has been a matter of increasing interest. In this context the function of neutrophils is controversial as neutrophils were shown to possess both tumor promoting and tumor limiting properties. Here we provide an up‐to‐date review of the pro‐ and antitumor properties neutrophils possess as well as the environmental cues that regulate these distinct functions.
Triggers, Inhibitors, Mechanisms, and Significance of Eryptosis: The Suicidal Erythrocyte Death
2015-01-01

Suicidal erythrocyte death or eryptosis is characterized by erythrocyte shrinkage, cell membrane blebbing, and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca 2+ entry, ceramide formation, stimulation of caspases, calpain activation, energy depletion, oxidative stress, and dysregulation of several kinases. Eryptosis is triggered by a wide variety of xenobiotics. It is inhibited by several xenobiotics and endogenous molecules including NO and erythropoietin. The susceptibility of erythrocytes to eryptosis increases with erythrocyte age. Phosphatidylserine exposing erythrocytes adhere to the vascular wall by binding to endothelial CXC-Motiv-Chemokin-16/Scavenger-receptor for phosphatidylserine and oxidized low density lipoprotein (CXCL16). Phosphatidylserine exposing erythrocytes are further engulfed by phagocytosing cells and are thus rapidly cleared from circulating blood. Eryptosis eliminates infected or defective erythrocytes thus counteracting parasitemia in malaria and preventing detrimental hemolysis of defective cells. Excessive eryptosis, however, may lead to anemia and may interfere with microcirculation. Enhanced eryptosis contributes to the pathophysiology of several clinical disorders including metabolic syndrome and diabetes, malignancy, cardiac and renal insufficiency, hemolytic uremic syndrome, sepsis, mycoplasma infection, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose 6-phosphate dehydrogenase deficiency, and Wilson’s disease. Facilitating or inhibiting eryptosis may be a therapeutic option in those disorders.
Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
2015-01-01

Chronic obstructive lung disease determines morbidity and mortality of patients with cystic fibrosis (CF). CF airways are characterized by a nonresolving neutrophilic inflammation. After pathogen contact or prolonged activation, neutrophils release DNA fibres decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). NETs have been described to act in a beneficial way for innate host defense by bactericidal, fungicidal, and virucidal actions. On the other hand, excessive NET formation has been linked to the pathogenesis of autoinflammatory and autoimmune disease conditions. We quantified free DNA structures characteristic of NETs in airway fluids of CF patients and a mouse model with CF‐like lung disease. Free DNA levels correlated with airflow obstruction, fungal colonization, and CXC chemokine levels in CF patients and CF‐like mice. When viewed in combination, our results demonstrate that neutrophilic inflammation in CF airways is associated with abundant free DNA characteristic for NETosis, and suggest that free DNA may be implicated in lung function decline in patients with CF.
Neurofeedback, Self-Regulation, and Brain Imaging: Clinical Science and Fad in the Service of Mental Disorders
2015-01-01

Neurofeedback draws on multiple techniques that propel both healthy and patient populations to self-regulate neural activity. Since the 1970s, numerous accounts have promoted electroencephalography-neurofeedback as a viable treatment for a host of mental disorders. Today, while the number of health care providers referring patients to neurofeedback practitioners increases steadily, substantial methodological and conceptual caveats continue to pervade empirical reports. And yet, nascent imaging technologies (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous protocols are paving the road towards more effective applications and a better scientific understanding of the underlying mechanisms. Here, we outline common neurofeedback methods, illuminate the tenuous state of the evidence, and sketch out future directions to further unravel the potential merits of this contentious therapeutic prospect.