bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple bespoke preservation of two conservation laws
Authors: Frasca-Caccia Gianluca , Hydon Peter Ellsworth 
Published: November 2018

AbstractConservation laws are among the most fundamental geometric properties of a partial differential equation (PDE), but few known finite difference methods preserve more than one conservation law. All conservation laws belong to the kernel of the Euler operator, an observation that was first used recently to construct approximations symbolically that preserve two conservation laws of a given PDE. However, the complexity of the symbolic computations has limited the effectiveness of this approach. The current paper introduces some key simplifications that make the symbolic–numeric approach feasible. To illustrate the simplified approach we derive bespoke finite difference schemes that preserve two discrete conservation laws for the Korteweg–de Vries equation and for a nonlinear heat equation. Numerical tests show that these schemes are robust and highly accurate compared with others in the literature.
Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar
Authors: Chaumeau Victor , Kajeechiwa Ladda , Fustec Bénédicte , Landier Jordi , Naw Nyo Saw , Nay Hsel Saw , Phatharakokordbun Phabele , Kittiphanakun Prapan , Nosten Suphak , Thwin May Myo , Win Tun Saw , Wiladphaingern Jacher , Cottrell Gilles , Parker Daniel M , Minh Myo Chit , Kwansomboon Nittpha , Metaane Selma , Montazeau Céline , Kunjanwong Kitti , Sawasdichai Sunisa , Andolina Chiara , Ling Clare , Haohankhunnatham Warat , Christiensen Peter , Wanyatip Sunaree , Konghahong Kamonchanok , Cerqueira Dominique , Imwong Mallika , Dondorp Arjen M , Chareonviriyaphap Theeraphap , White Nicholas J , Nosten François H , Corbel Vincent 
Published: November 2018

Abstract

Background
The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously.

Methods
MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression.

Results
Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6–100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8–6.0-fold) increase in the vector infection rate.

Conclusion
Asymptomatic infections are a major source of malaria transmission in Southeast Asia.
Emerging threat of triazole-resistant Aspergillus fumigatus
Authors: Rybak Jeffrey M , Fortwendel Jarrod R , Rogers P David 
Published: November 2018

AbstractInvasive aspergillosis is a leading cause of morbidity and mortality among immunocompromised populations and is predicted to cause more than 200 000 life-threatening infections each year. Aspergillus fumigatus is the most prevalent pathogen isolated from patients with invasive aspergillosis, accounting for more than 60% of all cases. Currently, the only antifungal agents available with consistent activity against A. fumigatus are the mould-active triazoles and amphotericin B, of which the triazoles commonly represent both front-line and salvage therapeutic options. Unfortunately, the treatment of infections caused by A. fumigatus has recently been further complicated by the global emergence of triazole resistance among both clinical and environmental isolates. Mutations in the A. fumigatus sterol-demethylase gene cyp51A, overexpression of cyp51A and overexpression of efflux pump genes are all known to contribute to resistance, yet much of the triazole resistance among A. fumigatus still remains unexplained. Also lacking is clinical experience with therapeutic options for the treatment of triazole-resistant A. fumigatus infections and mortality associated with these infections remains unacceptably high. Thus, further research is greatly needed to both better understand the emerging threat of triazole-resistant A. fumigatus and to develop novel therapeutic strategies to combat these resistant infections.
Tfp, News, and “Sentiments”: the International Transmission of Business Cycles
Authors: Levchenko Andrei A , Pandalai-Nayar Nitya 
Published: November 2018

AbstractWe propose a novel identification scheme for a nontechnology business cycle shock, which we label “sentiment”. This is a shock orthogonal to identified surprise and news TFP shocks that maximize the short-run forecast error variance of an expectational variable, alternatively a GDP forecast or a consumer confidence index. We then estimate the international transmission of three identified shocks—surprise TFP, news of future TFP, and sentiment—from the United States to Canada. The US sentiment shock produces a business cycle in the United States, with output, hours, and consumption rising following a positive shock, and accounts for the bulk of the US short-run business cycle fluctuations. The sentiment shock also has a significant impact on Canadian macroaggregates. In the short run, it is more important than either the surprise or the news TFP shocks in generating business cycle comovement between the United States and Canada, accounting for over 40% of the forecast error variance of Canadian GDP and over one-third of Canadian hours, imports, and exports. The news shock is responsible for some comovement at 5–10 years, and surprise TFP innovations do not generate synchronization. We provide a simple theoretical framework to illustrate how the US sentiment shocks can transmit to Canada.
Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1
Authors: Rusnak Lauren , Tang Cong , Qi Qi , Mo Xiulei , Fu Haian 
Published: November 2018

Abstract
Apoptosis signal-regulating kinase 1 (ASK1) is an important mediator of the cell stress response pathways. Because of its central role in regulating cell death, the activity of ASK1 is tightly regulated by protein–protein interactions and post-translational modifications. Deregulation of ASK1 activity has been linked to human diseases, such as neurological disorders and cancer. Here we describe the identification and characterization of large tumor suppressor 2 (LATS2) as a novel binding partner for ASK1. LATS2 is a core kinase in the Hippo signaling pathway and is commonly downregulated in cancer. We found that LATS2 interacts with ASK1 and increases ASK1-mediated signaling to promote apoptosis and activate the JNK mitogen-activated protein kinase (MAPK). This change in MAPK signaling is dependent on the catalytic activity of ASK1 but does not require LATS2 kinase activity. This work identifies a novel role for LATS2 as a positive regulator of the ASK1–MKK–JNK signaling pathway and establishes a kinase-independent function of LATS2 that may be part of the intricate regulatory system for cellular response to diverse stress signals.
Overexpression of ubiquitin-specific peptidase 15 in systemic sclerosis fibroblasts increases response to transforming growth factor β
Authors: Galant Christine , Marchandise Joel , Stoenoiu Maria S , Ducreux Julie , De Groof Aurélie , Pirenne Sophie , Van den Eynde Benoit , Houssiau Frédéric A , Lauwerys Bernard R 
Published: November 2018

Abstract

Objective
Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-β signalling in primary fibroblast cell lines.

Methods
High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-β stimulation.

Results
Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt/TGF-β signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-β induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-β-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action.

Conclusion
Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-β, and is a potential therapeutic target in SSc.
Phylogeny and molecular species delimitation of long-nosed armadillos (Dasypus: Cingulata) supports morphology-based taxonomy
Authors: Feijó Anderson , Vilela Júlio F , Cheng Jilong , Schetino Marco Antônio A , Coimbra Raphael T F , Bonvicino Cibele R , Santos Fabrício R , Patterson Bruce D , Cordeiro-Estrela Pedro 
Published: November 2018

AbstractThe armadillo genus Dasypus is the most species-rich and widely distributed genus of the order Cingulata and it has a dynamic taxonomic history. Recent morphology-based studies have proposed new taxonomic arrangements, but these were not yet assessed with molecular data. The two comprehensive phylogenetic hypotheses available for the genus are conflicting and were each based on a subset of taxa, hampering a proper evaluation of species boundaries. Using a multilocus molecular dataset, based on the broadest geographic sampling of Dasypus to date, we inferred the phylogenetic relationships of all species of the genus, including the recently reinstated D. beniensis and D. pastasae. We tested recent taxonomic hypotheses using several species-delimitation approaches. Our phylogeny recovered three main lineages of long-nosed armadillos that we treat as subgenera (Hyperoambon, Muletia and Dasypus) and identified the majority of its diversification as having occurred during the Pliocene. Molecular species delimitation supported morphological evidence in assigning D. hybridus as a subspecies of D. septemcinctus and confirming the split of the D. kappleri complex into three species. Our results strongly support the recognition of Guiana Shield populations formerly assigned to D. novemcinctus as a distinct species. The phylogenetic positions of D. mazzai and D. sabanicola remain uncertain. Further investigation using faster-evolving genes and additional samples may help to clarify the relationships of these young species.
The human secretome – the proteins secreted from human cells
Authors: Uhlen Mathias , Tegel Hanna , Sivertsson Åsa , Kuo Chih-Chung , Gutierrez Jahir M. , Lewis Nathan E. , Forsström Björn , Dannemeyer Melanie , Fagerberg Linn , Malm Magdalena , Vunk Helian , Edfors Fredrik , Hober Andreas , Sjöstedt Evelina , Kotol David , Mulder Jan , Mardinoglu Adil , Schwenk Jochen M. , Nilsson Peter , Zwahlen Martin , Takanen Jenny Ottosson , von Feilitzen Kalle , Stadler Charlotte , Lindskog Cecilia , Ponten Fredrik , Nielsen Jens , Palsson Bernhard O. , Volk Anna-Luisa , Lundqvist Magnus , Berling Anna , Svensson Anne-Sophie , Kanje Sara , Enstedt Henric , Afshari Delaram , Ekblad Siri , Scheffel Julia , Katona Borbala , Vuu Jimmy , Lindström Emil , Xu LanLan , Mihai Roxana , Bremer Lucas , Westin Malin , Muse Muna , Mayr Lorenz M. , Knight Sinead , Göpel Sven , Davies Rick , Varley Paul , Hatton Diane , Fields Ray , Voldborg Bjørn G. , Rockberg Johan , Schiavone Lovisa Holmberg , Hober Sophia 
Published: November 2018

AbstractThe proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving β-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.
Hepatocyte Membrane Potential Regulates Serum Insulin and Insulin Sensitivity by Altering Hepatic GABA Release
Authors: Geisler Caroline. E. , Ghimire Susma. , Hepler Chelsea. , Miller Kendra E. , Higgins Mark. R. , Yoshino Jun. , Klein Samuel. , Renquist Benjamin. J. 
Published: November 2018

AbstractThe degree of hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Here, we propose a mechanism that explains this associative link, whereby, hepatic steatosis dysregulates glucose and insulin homeostasis. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type II diabetes mellitus. Herein, we identify GABA as a novel hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity.
Identification and expression ofLactobacillus paracaseigenes for adaptation to desiccation and rehydration
Authors: Palud Aurore , Salem Karima , Cavin Jean-François , Beney Laurent , Licandro Hélène 
Published: November 2018

AbstractLactobacillus paracaseiis able to persist in a variety of natural and technological environments despite physico-chemical perturbations, in particular alternations between desiccation and rehydration. However, the way in which it adapts to hydric fluctuations and in particular the genetic determinants involved are not clearly understood. To identify the genes involved in adaptation to desiccation, an annotated library ofL. paracaseirandom transposon mutants was screened for viability after desiccation (25% relative humidity, 25°C). Subsequently, the expression of the identified genes was measured at five stages of the dehydration-rehydration process to formulate the chronology of gene expression. The 24 identified genes were related to metabolism and transport, membrane function and structure, regulation of stress response, DNA related enzymes and environmental sensing. They were classified into four different transcriptomic profiles, in particular genes upregulated during both desiccation and rehydration phases and genes upregulated during the desiccation phase only. Thus, genetic response to hydric fluctuations seems to occur during desiccation and can continue or not during rehydration. The genes identified should contribute to improving the stabilization of lactobacillus starters in dry state.ImportanceSince water is the fundamental component of all living organisms, desiccation and rehydration alternation is one of the most prevalent and severe stresses for most microorganisms. Adaptation to this stress occurs via a combination of mechanisms which depend on the genetic background of the microorganism. InL. paracasei,we developed a strategy to identify genes involved in the adaptation to hydric fluctuations using random transposon mutagenesis and targeted transcriptomics. Both dehydration and rehydration were studied to decipher the chronology of genetic mechanisms. We found 24 as yet unidentified genes involved in this response. Most of them are linked to either the transport of molecules or to cell wall structure and function. Our screening also identified genes for environment sensing and two alarmones necessary forL. paracaseisurvival. Furthermore, our results show that desiccation is a critical phase for inducing stress response inL. paracasei.
Natural copy number differences of tandemly repeated small nucleolar RNAs in the Prader-Willi syndrome genomic region regulate individual behavioral responses in mammals
Authors: Keshavarz Maryam , Krebs-Wheaton Rebecca , Refki Peter , Savriama Yoland , Zhang Yi , Guenther Anja , Brückl Tanja M. , Binder Elisabeth B. , Tautz Diethard 
Published: November 2018

AbstractThe Prader-Willi Syndrome (PWS) gene region is an imprinted gene complex involved in behavioral, metabolic and osteogenic functions. We have analyzed here the variation of two families of regulatory small nucleolar RNAs (SNORD115 and SNORD116) that are coded within the PWS and are expressed from the paternal chromosome. They are organized in two tandemly repeated clusters which are naturally copy number variable between individuals. We find that the copy numbers at these loci correlate with repeatable individual test scores for anxiety that are considered to constitute a component of the “personality” of individuals. We show this for different populations and species of mice, cavies and for the anxiety component of personality tests in humans. This is also the case for an inbred mouse strain (C57Bl6) implying that copy number variation creates phenotypic variability even in an isogenic background. In transcriptome data from brain samples of this strain we find SNORD copy-number correlated regulation of target genes that are known to be involved in influencing behavior. SNORD115 has previously been suggested to regulate splicing of the serotonin receptor Htr2c and we confirm this in our data. For SNORD116 we provide evidence that it regulates the expression level of the chromatin regulator Ankrd11, which itself regulates GABA receptors, metabolic pathways, cell differentiation and osteogenesis. Intriguingly, we find that craniofacial shapes in mice correlate also with SNORD116 copy numbers. New copy number variants are generated at very high rates in mice, possibly at every generation, explaining why conventional genetic mapping could not detect this association. Our results suggest that the variable dosage of two regulatory RNAs are major determinants of individual behavioral differences and correlated traits in mammals.
Dispersal increases the resilience of tropical savanna and forest distributions
Authors: Goel Nikunj , Guttal Vishwesha , Levin Simon A. , Staver Carla A. 
Published: November 2018

AbstractGlobal change may induce changes in savanna and forest distributions, but the dynamics of these changes remain unclear. Classical biome theory suggests that climate is predictive of biome distributions, such that shifts will be continuous and reversible. This view, however, cannot explain a widely observed mismatch between climate and tree cover, which some argue results from fire-vegetation feedbacks maintaining savanna and forest as bistable states, such that, instead, shifts will be discontinuous and irreversible. This bistable model, however, cannot reproduce the spatial aggregation of biomes. Here, we suggest that both models are limited in that they ignore spatial processes, such as dispersal. We examine the contributions of dispersal to determining savanna and forest distributions using a reaction-diffusion model, comparing results qualitatively to empirical savanna and forest distributions in Africa. The diffusion model induces spatially aggregated distributions, separated by a stable savanna-forest boundary. The equilibrium position of that boundary depends not only on precipitation but also on the curvature of precipitation contours with some history dependence (although less than in the bistable model). This model predicts different dynamics in response to global change: the boundary continuously tracks climate, recovering following disturbances, unless remnant biome patches are too small.
Topological gene-expression networks recapitulate brain anatomy and function
Authors: Patania Alice , Selvaggi Pierluigi , Veronese Mattia , Dipasquale Ottavia , Expert Paul , Petri Giovanni 
Published: November 2018

AbstractUnderstanding how gene expression translates to and affects human behaviour is one of the ultimate aims of neuroscience. In this paper, we present a pipeline based on Mapper, a topological simplification tool, to produce and analyze genes co-expression data. We first validate the method by reproducing key results from the literature on the Allen Human Brain Atlas, and the correlations between resting-state fMRI and gene co-expression maps. We then analyze a dopamine-related gene-set and find that co-expression networks produced by Mapper returned a structure that matches the well-known anatomy of the dopaminergic pathway. Our results suggest that topological network descriptions can be a powerful tool to explore the relationships between genetic pathways and their association with brain function and its perturbation due to illness and/or pharmacological challenge.