bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global transcriptional repression: An initial and essential step for
Plasmodium
sexual development
Authors: Yuda Masao , Iwanaga Shiroh , Kaneko Izumi , Kato Tomomi 
Published: September 2015

Significance
In malaria parasites, gametocytogenesis is a process whereby gametocytes, the precursors of gametes, are generated from asexual blood-stage parasites. In this study, we report that the plasmodium transcriptional repressor AP2-G2 plays an essential role in this process. We found that AP2-G2 represses the genes that are required for the proliferation of the asexual stage and, thereby, supports the conversion from the asexual blood stage to the nonreplicative sexual stage. Similarly, during the initial phase of germ-line formation in metazoan animals (including insects), a master transcriptional repressor specifies primordial germ cells among embryonic cells. Thus, our findings suggest that the basic molecular mechanisms that are required to establish the germ line have been conserved in eukaryotes, despite their evolutionary divergence.
Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain
Authors: Rütgen Markus , Seidel Eva-Maria , Silani Giorgia , Riečanský Igor , Hummer Allan , Windischberger Christian , Petrovic Predrag , Lamm Claus 
Published: September 2015

SignificanceEmpathy is of major importance for everyday social interaction. Recent neuroscientific models suggest that pain empathy relies on the activation of brain areas that are also engaged during the first-hand experience of pain. These models rely on rather unspecific and correlational evidence. Here, we show that inducing pain analgesia also reduces pain empathy, and that this is associated with decreased activation of empathy-related brain areas. We then document that blocking placebo analgesia via an opioid antagonist also blocks placebo analgesia effects on pain empathy. This finding suggests that pain empathy is grounded in neural responses and neurotransmitter activity related to first-hand pain.
Topology-defined units in numerosity perception
Authors: He Lixia , Zhou Ke , Zhou Tiangang , He Sheng , Chen Lin 
Published: September 2015

Significance
What is a number? The answer to this age-old and fundamental question of philosophy has increasingly benefited from recent scientific investigation using psychology and neuroscience. To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for various low-level visual features in different tasks and across small and large numbers. Results were consistent with the topological account, namely that numbers were strongly influenced by topological invariants (connectivity and the inside/outside relationship): connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. Brain image results also provided evidence that numbers represented in the intraparietal sulcus were influenced by topology.
Ecosystem carbon stocks and sequestration potential of federal lands across the conterminous United States
Authors: Tan Zhengxi , Liu Shuguang , Sohl Terry L. , Wu Yiping , Young Claudia J. 
Published: September 2015

Significance
There has been a critical knowledge gap for national biological C sequestration potential assessment due to a lack of relevant information about federal lands that cover nearly 30% of the whole US territory. Here, we present the results from a multimodel simulation approach and fill the current knowledge gap by revealing the C sequestration potential of federal lands across the conterminous United States and their contribution to the national ecosystem C budget through 2050. This kind of information can be a fundamental reference for federal agencies to develop long-term strategies for mitigating greenhouse gas (GHG) emissions and sustaining federal land resources.
Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent ocular dominance plasticity and LTD in visual cortex
Authors: Sidorov Michael S. , Kaplan Eitan S. , Osterweil Emily K. , Lindemann Lothar , Bear Mark F. 
Published: September 2015

Significance
Interruption of normal sensory experience during early postnatal life often causes a permanent loss of synaptic strength in the brain and consequent functional impairment. For example, temporary monocular deprivation causes long-term depression (LTD) of synapses in the visual cortex of mammals, along with a profound loss of vision. The mechanisms by which this synaptic plasticity occurs are only partially understood. Here we show that signaling via metabotropic glutamate receptor 5 during a critical period of postnatal development establishes the biochemical conditions that are permissive for activity-dependent sculpting of excitatory synapses via the mechanism of NMDA receptor-dependent LTD.
Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b
+
dendritic cells
Authors: Linehan Jonathan L. , Dileepan Thamotharampillai , Kashem Sakeen W. , Kaplan Daniel H. , Cleary Patrick , Jenkins Marc K. 
Published: September 2015

Significance
Naïve helper T cells can differentiate into several specialized subtypes that help other cells kill microbes. The processes that determine how the different T-cell subtypes form in the body are not understood. Here we identify a population of dendritic cells that is responsible for the formation of one helper T-cell type during nasal infection. These results extend knowledge about T-cell specification and could be applied to improve vaccines for nasal pathogens.
Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth
Authors: Aye Irving L. M. H. , Rosario Fredrick J. , Powell Theresa L. , Jansson Thomas 
Published: September 2015

Significance
Obesity and metabolic syndrome may, in part, originate in fetal life. In particular, babies of mothers with obesity and/or gestational diabetes mellitus (GDM) are often large at birth and have increased adiposity, which predisposes them to the development of metabolic disease later in life. Maternal obesity and GDM are typically associated with low circulating levels of adiponectin (ADN), and we found that ADN supplementation to pregnant obese mice completely normalized the changes in placental function and prevented fetal overgrowth caused by maternal obesity. These findings suggest that strategies to increase ADN levels in maternal obesity and GDM may alleviate the adverse effects of these pregnancy complications on the fetus.
Computational probing protein–protein interactions targeting small molecules
Authors: Wang Yong-Cui , Chen Shi-Long , Deng Nai-Yang , Wang Yong 
Published: September 2015

Abstract
Motivation: With the booming of interactome studies, a lot of interactions can be measured in a high throughput way and large scale datasets are available. It is becoming apparent that many different types of interactions can be potential drug targets. Compared with inhibition of a single protein, inhibition of protein–protein interaction (PPI) is promising to improve the specificity with fewer adverse side-effects. Also it greatly broadens the drug target search space, which makes the drug target discovery difficult. Computational methods are highly desired to efficiently provide candidates for further experiments and hold the promise to greatly accelerate the discovery of novel drug targets.
Results: Here, we propose a machine learning method to predict PPI targets in a genomic-wide scale. Specifically, we develop a computational method, named as PrePPItar, to Predict PPIs as drug targets by uncovering the potential associations between drugs and PPIs. First, we survey the databases and manually construct a gold-standard positive dataset for drug and PPI interactions. This effort leads to a dataset with 227 associations among 63 PPIs and 113 FDA-approved drugs and allows us to build models to learn the association rules from the data. Second, we characterize drugs by profiling in chemical structure, drug ATC-code annotation, and side-effect space and represent PPI similarity by a symmetrical S-kernel based on protein amino acid sequence. Then the drugs and PPIs are correlated by Kronecker product kernel. Finally, a support vector machine (SVM), is trained to predict novel associations between drugs and PPIs. We validate our PrePPItar method on the well-established gold-standard dataset by cross-validation. We find that all chemical structure, drug ATC-code, and side-effect information are predictive for PPI target. Moreover, we can increase the PPI target prediction coverage by integrating multiple data sources. Follow-up database search and pathway analysis indicate that our new predictions are worthy of future experimental validation.
Conclusion: In conclusion, PrePPItar can serve as a useful tool for PPI target discovery and provides a general heterogeneous data integrative framework.
Availability and implementation: PrePPItar is available at http://doc.aporc.org/wiki/PrePPItar.
Contact: ycwang@nwipb.cas.cn or ywang@amss.ac.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Drug-set enrichment analysis: a novel tool to investigate drug mode of action
Authors: Napolitano Francesco , Sirci Francesco , Carrella Diego , di Bernardo Diego 
Published: September 2015

Abstract
Motivation: Automated screening approaches are able to rapidly identify a set of small molecules inducing a desired phenotype from large small-molecule libraries. However, the resulting set of candidate molecules is usually very diverse pharmacologically, thus little insight on the shared mechanism of action (MoA) underlying their efficacy can be gained.
Results: We introduce a computational method (Drug-Set Enrichment Analysis—DSEA) based on drug-induced gene expression profiles, which is able to identify the molecular pathways that are targeted by most of the drugs in the set. By diluting drug-specific effects unrelated to the phenotype of interest, DSEA is able to highlight phenotype-specific pathways, thus helping to formulate hypotheses on the MoA shared by the drugs in the set. We validated the method by analysing five different drug-sets related to well-known pharmacological classes. We then applied DSEA to identify the MoA shared by drugs known to be partially effective in rescuing mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene function in Cystic Fibrosis.
Availability and implementation: The method is implemented as an online web tool publicly available at http://dsea.tigem.it.
Contact: dibernardo@tigem.it
Supplementary information: Supplementary data are available at Bioinformatics online.
Cytoscape.js: a graph theory library for visualisation and analysis
Authors: Franz Max , Lopes Christian T. , Huck Gerardo , Dong Yue , Sumer Onur , Bader Gary D. 
Published: September 2015

Abstract
Summary: Cytoscape.js is an open-source JavaScript-based graph library. Its most common use case is as a visualization software component, so it can be used to render interactive graphs in a web browser. It also can be used in a headless manner, useful for graph operations on a server, such as Node.js.
Availability and implementation: Cytoscape.js is implemented in JavaScript. Documentation, downloads and source code are available at http://js.cytoscape.org.
Contact: gary.bader@utoronto.ca
XPIWIT—an XML pipeline wrapper for the Insight Toolkit
Authors: Bartschat Andreas , Hübner Eduard , Reischl Markus , Mikut Ralf , Stegmaier Johannes 
Published: September 2015

Abstract
Summary: The Insight Toolkit offers plenty of features for multidimensional image analysis. Current implementations, however, often suffer either from a lack of flexibility due to hard-coded C++ pipelines for a certain task or by slow execution times, e.g. caused by inefficient implementations or multiple read/write operations for separate filter execution. We present an XML-based wrapper application for the Insight Toolkit that combines the performance of a pure C++ implementation with an easy-to-use graphical setup of dynamic image analysis pipelines. Created XML pipelines can be interpreted and executed by XPIWIT in console mode either locally or on large clusters. We successfully applied the software tool for the automated analysis of terabyte-scale, time-resolved 3D image data of zebrafish embryos.
Availability and implementation: XPIWIT is implemented in C++ using the Insight Toolkit and the Qt SDK. It has been successfully compiled and tested under Windows and Unix-based systems. Software and documentation are distributed under Apache 2.0 license and are publicly available for download at https://bitbucket.org/jstegmaier/xpiwit/downloads/.
Contact: johannes.stegmaier@kit.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Political Centralization and Government Accountability *
Authors: Boffa Federico , Piolatto Amedeo , Ponzetto Giacomo A. M. 
Published: September 2015

AbstractThis article explains why decentralization can undermine accountability and answers three questions: what determines if power should be centralized or decentralized when regions are heterogeneous? How many levels of government should there be? How should state borders be drawn? We develop a model of political agency in which voters differ in their ability to monitor rent-seeking politicians. We find that rent extraction is a decreasing and convex function of the share of informed voters, because voter information improves monitoring but also reduces the appeal of holding office. As a result, information heterogeneity pushes toward centralization to reduce rent extraction. Taste heterogeneity pulls instead toward decentralization to match local preferences. Our model thus implies that optimal borders should cluster by tastes but ensure diversity of information. We also find economies of scope in accountability that explain why multiplying government tiers harms efficiency. A single government in charge of many policies has better incentives than many special-purpose governments splitting its budget and responsibilities. Hence, a federal system is desirable only if information varies enough across regions.
Fiber-optic Monitoring of Spinal Cord Hemodynamics in Experimental Aortic Occlusion
Authors: Kogler Angela S. , Bilfinger Thomas V. , Galler Robert M. , Mesquita Rickson C. , Cutrone Michael , Schenkel Steven S. , Yodh Arjun G. , Floyd Thomas F. 
Published: September 2015

AbstractAbstract
The fiber-optic probe can be placed percutaneously into the epidural space of anesthetized sheep. Changes in blood flow detected by the probe correlated with microsphere-detected changes in spinal cord blood flow during occlusion and deocclusion of the thoracic aorta. Changes in spinal cord blood flow detected by the fiber-optic probe were markedly more rapid in onset than functional changes detected by motor-evoked responses.
Supplemental Digital Content is available in the text.

Background
Spinal cord ischemia occurs frequently during thoracic aneurysm repair. Current methods based on electrophysiology techniques to detect ischemia are indirect, non-specific, and temporally slow. In this article, the authors report the testing of a spinal cord blood flow and oxygenation monitor, based on diffuse correlation and optical spectroscopies, during aortic occlusion in a sheep model.

Methods
Testing was carried out in 16 Dorset sheep. Sensitivity in detecting spinal cord blood flow and oxygenation changes during aortic occlusion, pharmacologically induced hypotension and hypertension, and physiologically induced hypoxia/hypercarbia was assessed. Accuracy of the diffuse correlation spectroscopy measurements was determined via comparison with microsphere blood flow measurements. Precision was assessed through repeated measurements in response to pharmacologic interventions.

Results
The fiber-optic probe can be placed percutaneously and is capable of continuously measuring spinal cord blood flow and oxygenation preoperatively, intraoperatively, and postoperatively. The device is sensitive to spinal cord blood flow and oxygenation changes associated with aortic occlusion, immediately detecting a decrease in blood flow (−65 ± 32%; n = 32) and blood oxygenation (−17 ± 13%, n = 11) in 100% of trials. Comparison of spinal cord blood flow measurements by the device with microsphere measurements led to a correlation of R
2 = 0.49, P < 0.01, and the within-sheep coefficient of variation was 9.69%. Finally, diffuse correlation spectroscopy is temporally more sensitive to ischemic interventions than motor-evoked potentials.

Conclusion
The first-generation spinal fiber-optic monitoring device offers a novel and potentially important step forward in the monitoring of spinal cord ischemia.
Pancreatitis Subtypes Survey in 852 Childhood‐Onset Systemic Lupus Erythematosus Patients
Authors: Marques Victor L.S. , Gormezano Natali W.S. , Bonfá Eloisa , Aikawa Nadia E. , Terreri Maria T. , Pereira Rosa M. , Magalhães Claudia S. , Guariento Andressa , Appenzeller Simone , Ferriani Virgínia P. , Barbosa Cássia M. , Ramos Valéria C. , Lotufo Simone , Silva Clovis A. 
Published: September 2015

ABSTRACTObjective:Pancreatitis is a rare and a life‐threatening systemic lupus erythematosus (SLE) manifestation in childhood‐onset SLE (cSLE). The objective of this study was to systematically classify pancreatitis in cSLE according to the International Study Group of Pediatric Pancreatitis and determine the overall prevalence, clinical features, laboratory, and first episode outcomes.Methods:A multicenter cohort study in 10 pediatric rheumatology centers, including 852 patients with cSLE.Results:Pancreatitis was diagnosed in 22 of 852 (2.6%) patients with cSLE. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%), and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis, or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration (1 [0–10] vs 4 [0–23] years, P < 0.0001) and higher median of Systemic Lupus Erythematosus Disease Activity Index 2000 (21 [0–41] vs 2 [0–45], P < 0.0001). The frequencies of fever (P < 0.0001), weight loss (P < 0.0001), serositis (P < 0.0001), nephritis (P < 0.0001), arterial hypertension (P < 0.0001), acute renal failure (P < 0.0001), macrophage activation syndrome (P < 0.0001), and death (P = 0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (P < 0.0001) and the median of prednisone dose (55 [15–60] vs 11 [1–90] mg/day, P < 0.0001) were significantly higher in patients with pancreatitis. Of note, the 2 patients with acute recurrent pancreatitis had 2 episodes, with pain‐free interval of 1 and 4 years.Conclusions:This was the first study characterizing pancreatitis using the International Study Group of Pediatric Pancreatitis standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.
Mechanism-based sirtuin enzyme activation
Authors: Guan Xiangying , Upadhyay Alok , Munshi Sudipto , Chakrabarti Raj 
Published: September 2015

AbstractSirtuin enzymes are NAD+-dependent protein deacylases that play a central role in the regulation of healthspan and lifespan in organisms ranging from yeast to mammals. There is intense interest in the activation of the seven mammalian sirtuins (SIRT1-7) in order to extend mammalian healthspan and lifespan. However, there is currently no understanding of how to design sirtuin-activating compounds beyond allosteric activators of SIRT1-catalyzed reactions that are limited to particular substrates. Moreover, across all families of enzymes, only a dozen or so distinct classes of non-natural small molecule activators have been characterized, with only four known modes of activation among them. None of these modes of activation are based on the unique catalytic reaction mechanisms of the target enzymes. Here, we report a general mode of sirtuin activation that is distinct from the known modes of enzyme activation. Based on the conserved mechanism of sirtuin-catalyzed deacylation reactions, we establish biophysical properties of small molecule modulators that can in principle result in enzyme activation for diverse sirtuins and substrates. Building upon this framework, we propose strategies for the identification, characterization and evolution of hits for mechanism-based enzyme activating compounds. We characterize several small molecules reported in the literature to activate sirtuins besides SIRT1, using a variety of biochemical and biophysical techniques including label-free and labeled kinetic and thermodynamic assays with multiple substrates and protocols for the identification of false positives. We provide evidence indicating that several of these small molecules reported in the published literature are false positives, and identify others as hit compounds for the design of compounds that can activate sirtuins through the proposed mechanism-based mode of action.
Investigation of the cellular reprogramming phenomenon referred to as stimulus-triggered acquisition of pluripotency (STAP)
Authors: Niwa Hitoshi 
Published: September 2015

AbstractIn 2014, it was reported that strong external stimuli, such as a transient low-pH stressor, was capable of inducing the reprogramming of mammalian somatic cells, resulting in the generation of pluripotent cells (Obokata et al. 2014a, b). This cellular reprograming event was designated ‘stimulus-triggered acquisition of pluripotency’ (STAP) by the authors of these reports. However, after multiple instances of scientific misconduct in the handling and presentation of the data were brought to light, both reports were retracted. To investigate the actual scientific significance of the purported STAP phenomenon, we sought to repeat the original experiments based on the methods presented in the retracted manuscripts and other relevant information. As a result, we have confirmed that the STAP phenomenon as described in the original studies is not reproducible.