bluuebunny/crossref_metadata_2025_split huggingface dataset:
A theory for ecological survey methods to map individual distributions
Authors: Takashina Nao , Beger Maria , Kusumoto Buntarou , Rathnayake Suren , Possingham Hugh P. 
Published: May 2017

AbstractSpatially-explicit approaches are widely recommended for ecosystem management. The quality of the data, such as presence/absence or habitat maps, affects the management actions recommended, and is, therefore, key to management success. However, available data are often biased and incomplete. Previous studies have advanced ways to resolve data bias and missing data, but questions remain about how we design ecological surveys to develop a dataset through field surveys. Ecological surveys may have multiple spatial scales, including the spatial extent of the target ecosystem (observation window), the resolution for mapping individual distributions (mapping unit), and the survey area within each mapping unit (sampling unit). We developed an ecological survey method for mapping individual distributions by applying spatially-explicit stochastic models. We used spatial point processes to describe individual spatial placements using either random or clustering processes. We then designed ecological surveys with different spatial scales and individual detectability. We found that the choice of mapping unit affected the presence mapped fraction, and the fraction of the total individuals covered by the presence mapped patches. Tradeoffs were found between these quantities and the map resolution, associated with equivalent asymptotic behaviors for both metrics at sufficiently small and large mapping unit scales. Our approach enabled consideration of the effect of multiple spatial scales in surveys, and estimation of the survey outcomes such as the presence mapped fraction and the number of individuals situated in the presence detected units. The developed theory may facilitate management decision-making and inform the design of monitoring and data gathering.
Deciphering the developmental program in the ascidianCiona intestinalisjust prior to gastrulation
Authors: Harada Yoshito 
Published: May 2017

ABSTRACTThe embryo of the ascidianCiona intestinalisdisplays striking anatomical simplicity, with an invariant cleavage pattern during development. It has a monoploid genome like the model organismsDrosophila melanogasterandCaenorhabditis elegans, whereas vertebrates generally exhibit tetraploidy. In this study, I took advantage of these characteristics to investigate the development of the organism as one reverse-engineers an industrial product. First, the spatial expression of 211 genes was digitalized. Some genes showed variable expression patterns, which might reflect multiple snapshots of a single temporally dynamic expression at different times. Several developmental territories of the embryo were considered to be very similar to each other; however, this digitalization of gene expression patterns showed that differences occurred between individual blastomeres even within a single developmental territory. Furthermore,Ciona Brachyury(Ci-Bra) was expressed in those blastomeres in which bothFox (forkhead-box) A-aandZic (zinc-finger) Lwere expressed, these proteins being upstream regulators ofCi-Bra.The approach described enables the developmental program to be studiedin silico.SUMMARY STATEMENTA detailed expansion of our knowledge on an animal developmental program by using already published gene expression data with the aid of computers
Inheritance of OCT4 predetermines fate choice in human embryonic stem cells
Authors: Wolff Samuel C. , Dumitru Raluca , Kedziora Katarzyna M. , Dungee Cierra D. , Zikry Tarek M. , Haggerty Rachel A. , Cheng JrGang , Beltran Adriana S. , Purvis Jeremy E. 
Published: May 2017

AbstractClonal cells can make different fate decisions, but it is often unclear to what extent these decisions are autonomous or predetermined. Here, we introduce a live-cell reporter for the pluripotency factor OCT4 into human embryonic stem cells to understand how they choose between self-renewal and differentiation. By tracing the histories of individual cells over multiple generations, we found that cells whose offspring were destined to differentiate showed decreased expression of OCT4 long before exposure to the differentiation stimulus. OCT4 levels were lineage-dependent; however, during cell division, mother cells distributed OCT4 asymmetrically to daughters. The resulting ratio of OCT4 between sister cells—established within minutes of mitosis—was predictive of downstream fates: cells receiving a greater ratio of maternal OCT4 showed sustained OCT4 levels and a reduced capacity to differentiate. Our observations imply that the choice between two developmental fates is almost entirely predetermined at the time of cell birth through inheritance of a pluripotency factor.
Rearrangement Scenarios Guided by Chromatin Structure
Authors: Pulicani Sylvain , Simonaitis Pijus , Swenson Krister M. 
Published: May 2017

AbstractGenome architecture can be drastically modified through a succession of large-scale rearrangements. In the quest to infer accurate ancestral rearrangement scenarios, it is often the case that parsimony principal alone does not impose enough constraints. Thus, the current challenge is to consider more biological information in the inference process. In previous work, we introduced a model for such a task, based on a partition into equivalence classes of the adjacencies between genes. Such a partition is amenable to the representation of spacial constraints as given by Hi-C data. A major open question is the validity of such a model. In this note, we show that the quality of a clustering of the adjacencies based on Hi-C data is directly correlated to the quality of a rearrangement scenario that we compute betweenDrosophila melanogasterandD. yakuba.
Modules of co-occurrence in the cyanobacterial pan-genome
Authors: Beck Christian , Knoop Henning , Steuer Ralf 
Published: May 2017

ABSTRACTThe increasing availability of fully sequenced cyanobacterial genomes opens unprecedented opportunities to investigate the manifold adaptations and functional relationships that determine the genetic content of individual bacterial species. Here, we use comparative genome analysis to investigate the cyanobacterial pan-genome based on 77 strains whose complete genome sequence is available. Our focus is the co-occurrence of likely ortholog genes, denoted as CLOGs. We conjecture that co-occurrence CLOGs is indicative of functional relationships between the respective genes. Going beyond the analysis of pair-wise co-occurrences, we introduce a novel network approach to identify modules of co-occurring ortholog genes. Our results demonstrate that these modules exhibit a high degree of functional coherence and reveal known as well as previously unknown functional relationships. We argue that the high functional coherence observed for the extracted modules is a consequence of the similar-yet-diverse nature of the cyanobacterial phylum. We provide a simple toolbox that facilitates further analysis of our results with respect to specific cyanobacterial genes of interest.
Conserving Phylogenetic Diversity can be a Poor Strategy for Conserving Functional Diversity
Authors: Mazel Florent , Mooers Arne , Dalla Riva Giulio Valentino , Pennell Matthew W. 
Published: May 2017

AbstractFor decades, academic biologists have advocated for making conservation decisions in light of evolutionary history. Specifically, they suggest that policymakers should prioritize conserving phylogenetically diverse assemblages. The most prominent argument is that conserving phylogenetic diversity (PD) will also conserve diversity in traits and features (functional diversity; FD), which may be valuable for a number of reasons. The claim that PD-maximized (‘maxPD’) sets of taxa will also have high FD is often taken at face value and in cases where researchers have actually tested it, they have done so by measuring the phylogenetic signal in ecologically important functional traits. The rationale is that if traits closely mirror phylogeny, then saving the maxPD set of taxa will tend to maximize FD and if traits do not have phylogenetic structure, then saving the maxPD set of taxa will be no better at capturing FD than criteria that ignore PD. Here, we suggest that measuring the phylogenetic signal in traits is uninformative for evaluating the effectiveness of using PD in conservation. We evolve traits under several different models and, for the first time, directly compare the FD of a set of taxa that maximize PD to the FD of a random set of the same size. Under many common models of trait evolution and tree shapes, conserving the maxPD set of taxa will conserve more FD than conserving a random set of the same size. However, this result cannot be generalized to other classes of models. We find that under biologically plausible scenarios, using PD to select species can actually lead to less FD compared to a random set. Critically, this can occur even when there is phylogenetic signal in the traits. Predicting exactly when we expect using PD to be a good strategy for conserving FD is challenging, as it depends on complex interactions between tree shape and the assumptions of the evolutionary model. Nonetheless, if our goal is to maintain trait diversity, the fact that conserving taxa based on PD will not reliably conserve at least as much FD as choosing randomly raises serious concerns about the general utility of PD in conservation.
Arginase 1 is negatively regulated by β-catenin signaling in the lung
Authors: Sennello Joseph A. , Flozak Annette S. , Misharin Alexander V. , Gottardi Cara J. , Lam Anna P. 
Published: May 2017

ABSTRACTWe previously demonstrated that mice lacking the Wnt co-receptor, Lrp5, had attenuated pulmonary fibrosis in the bleomycin model. We found that Arginase 1 (Arg1), an enzyme that converts L-arginine to urea and ornithine, was markedly elevated inLrp5-/-lungs compared with wild-type mice after bleomycin injury. We show that this induction is not apparently due to the expression of Th2 cytokines, IL-4 and IL-13, but instead is due to Wnt/β-catenin signaling, which negatively regulates Arg1 expression in lung macrophages. Although Arg1 expression in macrophages has been used to define an alternatively activated phenotype, flow cytometry analysis of alveolar and interstitial macrophage sub-populations inLrp5-/-lungs 14 days after bleomycin injury revealed no clear evidence of skewing from a classical to an alternatively activated phenotype. Upregulation ofArg1expression and arginase activity might diminish lung arginine levels with consequent alterations in collagen or cytokine production. However, dietary supplementation of bleomycin-treatedLrp5-/-mice with the Arg1 substrate, L-arginine, failed to alter lung collagen content or cytokine levels 21 days after bleomycin injury. These findings demonstrate that Arg1 is negatively regulated by β-catenin signaling in macrophages, raising the possibility that Wnt signaling directs alterations in immune cell metabolism that may be relevant to lung repair after injury.
The core transcriptome of mammalian placentas and the divergence of expression with placental shape
Authors: Armstrong Don L. , McGowen Michael R. , Weckle Amy , Pantham Priyadarshini , Caravas Jason , Agnew Dalen , Benirschke Kurt , Savage-Rumbaugh Sue , Nevo Eviatar , Kim Chong J. , Wagner Günter P. , Romero Roberto , Wildman Derek E. 
Published: May 2017

AbstractIntroductionThe placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved.MethodUsing RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades.ResultsWe identified a set of 115 core genes which is expressed (FPKM≥10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2,ANXA1,S100A11,S100A10, andLGALS1), cell-cell interactions (LAMC1,LUM, andLGALS1), invasion (GRB2andRALB) and syncytialization (ANXA5andANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed inHomo sapienswhen compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, includingEREGandWNT5Awhich are both associated with placental shape.Discussion115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.
Prominent lateral spread of imaged evoked activity beyond cortical columns in barrel cortex provides foundation for coding whisker identity
Authors: Jacobs Nathan S. , Frostig Ron D. 
Published: May 2017

AbstractThe posterior medial barrel subfield (PMBSF) of rat primary somatosensory cortex exquisitely demonstrates topography and columnar organization, defining features of sensory cortices in the mammalian brain. Optical imaging and neuronal recordings in rat PMBSF demonstrates how evoked cortical activity following single whisker stimulation also rapidly spreads laterally into surrounding cortices, disregarding columnar and modality boundaries. The current study quantifies the spatial prominence of such lateral activity spreads by demonstrating that functional connectivity between laterally spaced cortical locations is actually stronger than between vertically spaced cortical locations. Further, the total amount of evoked activity within and beyond single column boundaries was quantified based on intrinsic signal optical imaging, single units and local field potentials (LFPs) recordings, revealing that the vast majority of whisker evoked activity in PMBSF occurs beyond columnar boundaries. Finally, a simple two layer artificial neural network model of PMBSF demonstrates the capacity of extra-columnar evoked activity spread to provide a foundation for accurate whisker stimulus classification that is robust to random scaling of inputs and local noise. Indeed, classification performance improved when more of the lateral spread was included in the model, providing further evidence for the relevance of the lateral spread.
Family or Money? The False Dilemma in Property Dispossession in Shanghai
Authors: Zhang Yunpeng 
Published: May 2017

AbstractThis article examines the lived experiences of property dispossession caused by the World Expo 2010 in Shanghai. Specifically, it examines the category of the family, which is overlooked in the existing literature, and probes into the political production of family conflicts and breakdowns. It characterizes the prevailing regime of dispossession in contemporary China as decentralized legal authoritarianism and argues that the organization of the Expo‐induced dispossession deviated from this because of the distinctive state structures involved. For this reason, tensions within the state apparatus were temporarily suspended, leading to reduced opportunity for resistance. The state's monopoly of symbolic production rendered contesting claims to property ownership illegitimate and made monetary compensation the only option. This turned confrontation with the state into domestic disputes. Organized as a state‐led project, dispossession also exploited displacees' past experiences of a ‘caring' state or state terror, giving rise to different attitudes towards displacement and thus causing more family disputes. Moreover, mobilization of the entire state apparatus also permitted the use of coercive and violent means without legal and moral concerns. Tactics that manipulated, and in some cases completely severed, relations within and beyond the displaced families are explored in depth. The article concludes with a call to change the ways that dispossession has been conceived and conducted in practice.
Optimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib
Authors: Lankheet Nienke A. G. , Desar Ingrid M. E. , Mulder Sasja F. , Burger David M. , Kweekel Dinemarie M. , van Herpen Carla M. L. , van der Graaf Winette T. A. , van Erp Nielka P. 
Published: May 2017

AimFixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring‐based dose optimization in daily practice.MethodsA cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow‐up drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing electronic patient records. Drug levels were measured using high‐performance liquid chromatography coupled with tandem mass spectrometry and trough levels were estimated using a predefined algorithm. Dose interventions were proposed based on trough levels.ResultsIn total, 396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed trough levels within the predefined target ranges despite standard dosing; 52% of the patients showed drug levels below and 10% above the target range. In 35 out of 41 patients (85%) dose interventions led to adequate trough levels. Eventually, 64% of the total cohort reached adequate trough levels.ConclusionsDose optimization proved an effective tool to reach adequate trough levels in patients treated with imatinib, sunitinib and pazopanib. The percentage of patients with adequate trough levels increased from 38 to 64%. Therapeutic drug monitoring may add to the improvement of efficacy and reduction of toxicity and costs of these treatments.
Modulation of Kv11.1 (hERG) channels by 5‐(((1H–indazol‐5‐yl)oxy)methyl)‐N‐(4‐(trifluoromethoxy)phenyl)pyrimidin‐2‐amine (ITP‐2), a novel small molecule activator
Authors: Sale Harinath , Roy Samrat , Warrier Jayakumar , Thangathirupathy Srinivasan , Vadari Yoganand , Gopal Shruthi K , Krishnamurthy Prasad , Ramarao Manjunath 
Published: May 2017

Background and PurposeActivators of Kv11.1 (hERG) channels have potential utility in the treatment of acquired and congenital long QT (LQT) syndrome. Here, we describe a new hERG channel activator, 5‐(((1H–indazol‐5‐yl)oxy)methyl)‐N‐(4‐(trifluoromethoxy)phenyl)pyrimidin‐2‐amine (ITP‐2), with a chemical structure distinct from previously reported compounds.Experimental ApproachConventional electrophysiological methods were used to assess the effects of ITP‐2 on hERG1a and hERG1a/1b channels expressed heterologously in HEK‐293 cells.Key ResultsITP‐2 selectively increased test pulse currents (EC50 1.0 μM) and decreased tail currents. ITP‐2 activated hERG1a homomeric channels primarily by causing large depolarizing shifts in the midpoint of voltage‐dependent inactivation and hyperpolarizing shifts in the voltage‐dependence of activation. In addition, ITP‐2 slowed rates of inactivation and made recovery from inactivation faster. hERG1a/1b heteromeric channels showed reduced sensitivity to ITP‐2 and their inactivation properties were differentially modulated. Effects on midpoint of voltage‐dependent inactivation and rates of inactivation were less pronounced for hERG1a/1b channels. Effects on voltage‐dependent activation and activation kinetics were not different from hERG1a channels. Interestingly, hERG1b channels were inhibited by ITP‐2. Inactivation‐impairing mutations abolished activation by ITP‐2 and led to inhibition of hERG channels. ITP‐2 exerted agonistic effect from extracellular side of the membrane and could activate one of the arrhythmia‐associated trafficking‐deficient LQT2 mutants.Conclusions and ImplicationsITP‐2 may serve as another novel lead molecule for designing robust activators of hERG channels. hERG1a/1b gating kinetics were differentially modulated by ITP‐2 leading to altered sensitivity. ITP‐2 is capable of activating an LQT2 mutant and may be potentially useful in the development of LQT2 therapeutics.
T and B cell clonal expansion in Ras-associated lymphoproliferative disease (RALD) as revealed by next-generation sequencing
Authors: Levy-Mendelovich S , Lev A , Rechavi E , Barel O , Golan H , Bielorai B , Neumann Y , Simon A J , Somech R 
Published: May 2017

Summary
Ras-associated lymphoproliferative disease (RALD) is an autoimmune lymphoproliferative syndrome (ALPS)-like disease caused by mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) or neuroblastoma RAS viral (V-Ras) oncogene homologue (NRAS). The immunological phenotype and pathogenesis of RALD have yet to be studied extensively. Here we report a thorough immunological investigation of a RALD patient with a somatic KRAS mutation. Patient lymphocytes were analysed for phenotype, immunoglobulin levels and T cell proliferation capacity. T and B cell receptor excision circles (TREC and KREC, respectively), markers of naive T and B cell production, were measured serially for 3 years. T and B cell receptor repertoires were studied using both traditional assays as well as next-generation sequencing (NGS). TREC and KREC declined dramatically with time, as did T cell receptor diversity. NGS analysis demonstrated T and B clonal expansions and marked restriction of T and B cell receptor repertoires compared to healthy controls. Our results demonstrate, at least for our reported RALD patient, how peripheral T and B clonal expansions reciprocally limit lymphocyte production and restrict the lymphocyte receptor repertoire in this disease. Decreased naive lymphocyte production correlated with a clinical deterioration in our patient's immune status, suggesting that TREC and KREC may be used as an aid in monitoring disease progression. Both the methodologies used here and the conclusions regarding immune homeostasis may be applicable to the research of ALPS and other immune dysregulation syndromes.
Measuring long‐term trends in policy coherence for development
Authors: Koch Dirk‐Jan 
Published: May 2017

AbstractThis article measures long term trends in policy coherence for development. Based on result chains, it develops a counterfactual methodology, and then applies it to assess changes in inputs, outputs and outcomes over time. While the literature does not indicate any significant change in policy coherence for development over the last decade, this research finds that, if the time scale is lengthened to 50 years, an overall increase in policy coherence for development of the Dutch government, vis‐à‐vis the DR Congo, in the domains of finance and security, can be detected. These changes in policy coherence for development inputs seem to have contributed, in conjunction with similar policies from other countries, in some instances, to positive outcomes in the DRC.