bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic Conflicts, Combinability, and Deep Phylogenomics in Plants
Authors: Smith Stephen A , Walker-Hale Nathanael , Walker Joseph F , Brown Joseph W 
Published: November 2019

Abstract
Studies have demonstrated that pervasive gene tree conflict underlies several important phylogenetic relationships where different species tree methods produce conflicting results. Here, we present a means of dissecting the phylogenetic signal for alternative resolutions within a data set in order to resolve recalcitrant relationships and, importantly, identify what the data set is unable to resolve. These procedures extend upon methods for isolating conflict and concordance involving specific candidate relationships and can be used to identify systematic error and disambiguate sources of conflict among species tree inference methods. We demonstrate these on a large phylogenomic plant data set. Our results support the placement of Amborella as sister to the remaining extant angiosperms, Gnetales as sister to pines, and the monophyly of extant gymnosperms. Several other contentious relationships, including the resolution of relationships within the bryophytes and the eudicots, remain uncertain given the low number of supporting gene trees. To address whether concatenation of filtered genes amplified phylogenetic signal for relationships, we implemented a combinatorial heuristic to test combinability of genes. We found that nested conflicts limited the ability of data filtering methods to fully ameliorate conflicting signal amongst gene trees. These analyses confirmed that the underlying conflicting signal does not support broad concatenation of genes. Our approach provides a means of dissecting a specific data set to address deep phylogenetic relationships while also identifying the inferential boundaries of the data set. [Angiosperms; coalescent; gene-tree conflict; genomics; phylogenetics; phylogenomics.]
Intraflagellar‐transport A dysfunction causes hyperphagia‐induced systemic insulin resistance in a pre‐obese state
Authors: Jacobs Damon T. , Allard Bailey A. , Pottorf Tana S. , Silva Luciane M. , Wang Wei , Al‐Naamani Aisha , Agborbesong Ewud , Wang Tao , Carr Dajanae A. , Tran Pamela V. 
Published: November 2019

AbstractDeletion of murine Thm1, an intraflagellar transport A (IFT‐A) component that mediates ciliary protein trafficking, causes hyperphagia, obesity, and metabolic syndrome. The role of Thm1 or IFT‐A in adipogenesis and insulin sensitivity is unknown. Here, we report that Thm1 knockdown in 3T3‐L1 pre‐adipocytes promotes adipogenesis and enhances insulin sensitivity in vitro. Yet, pre‐obese Thm1 conditional knockout mice show systemic insulin resistance. While insulin‐induced AKT activation in Thm1 mutant adipose depots and skeletal muscle are similar to those of control littermates, an attenuated insulin response arises in the mutant liver. Insulin treatment of control and Thm1 mutant primary hepatocytes results in similar AKT activation. Moreover, pair‐feeding Thm1 conditional knockout mice produces a normal insulin response, both in the liver and systemically. Thus, hyperphagia caused by a cilia defect, induces hepatic insulin resistance via a non‐cell autonomous mechanism. In turn, hepatic insulin resistance drives systemic insulin resistance prior to an obese phenotype. These data demonstrate that insulin signaling across cell types is regulated differentially, and that the liver is particularly susceptible to hyperphagia‐induced insulin resistance and a critical determinant of systemic insulin resistance.
Plagiarism in Brazil: A perspective of 25,000 PhD holders across the sciences
Authors: Vasconcelos Sonia MR , Masuda Hatisaburo , Sorenson Martha , Prosdocimi Francisco , Palácios Marisa , Watanabe Edson , Pinto José Carlos , Lapa e Silva José Roberto , Vieyra Adalberto , Pinto André , Mena-Chalco Jesús , Sant’Ana Mauricio , Roig Miguel 
Published: November 2019

AbstractWhen it comes to ownership of ideas in science, Robert K. Merton (1957) observed inPriorities in Scientific Discovery: A Chapter in the Sociology of Sciencethat “what is true of physics, chemistry, astronomy, medicine and mathematics is true also of all the other scientific disciplines, not excluding the social and psychological sciences”. However, consensus over related issues, such as what constitutes plagiarism in these fields cannot be taken for granted. We conducted a comprehensive study on plagiarism views among PhD holders registered in the database of the Brazilian National Council for Scientific and Technological Development (CNPq). We collected 25,157 valid responses encompassing views and attitudes toward plagiarism from a probability sample of PhD holders across the fields, including biologists, physicists, mathematicians, and engineers as well as linguists, philosophers and anthropologists. The results suggest that core principles about plagiarism are shared among this multidisciplinary community and that they corroborate Merton’s observations. Before this study, we could only speculate that this is the case. With these data from a probability sample of Brazilian academia (PhD holders), this study offers insight into the way plagiarism is perceived across the sciences, including the literature and arts, and sheds light on the problem in the context of international collaborative research networks. The data focus on a young research system in Latin America, but, given the cultural similarities that bind most Latin-American nations, these results may be relevant to other PhD populations in the region and should provide a comparison with studies from other emerging, non-Anglophone regions.
Dual-sensing genetically encoded fluorescent indicators resolve the spatiotemporal coordination of cytosolic abscisic acid and second messenger dynamics in Arabidopsis
Authors: Waadt Rainer , Köster Philipp , Andrés Zaida , Waadt Christian , Bradamante Gabriele , Lampou Konstantinos , Kudla Jörg , Schumacher Karin 
Published: November 2019

ABSTRACTDeciphering signal transduction processes is crucial for understanding how plants sense and respond to environmental changes. Various chemical compounds function as central messengers within deeply intertwined signaling networks. How such compounds act in concert remains to be elucidated. We have developed dual-sensing genetically encoded fluorescent indicators (2-In-1-GEFIs) for multiparametric in vivo analyses of the phytohormone abscisic acid (ABA), Ca2+, protons (H+), chloride (anions), the glutathione redox potential (EGSH) and hydrogen peroxide (H2O2). Simultaneous analyses of two signaling compounds in Arabidopsis (Arabidopsis thaliana) roots revealed that ABA treatment and uptake did not trigger rapid cytosolic Ca2+or H+fluxes. Glutamate, ATP, Arabidopsis PLANT ELICITOR PEPTIDE (AtPEP1) and glutathione disulfide (GSSG) treatments induced rapid spatiotemporally overlapping cytosolic Ca2+, H+and anion fluxes, but except for GSSG only weakly affected the cytosolic redox state. Overall, 2-In-1-GEFIs enable complementary high-resolution in vivo analyses of signaling compound dynamics and facilitate an advanced understanding of the spatiotemporal coordination of signal transduction processes in Arabidopsis.
Identification of hemicatenane-specific binding proteins by fractionation of Hela nuclei extracts
Authors: Rouis Oumayma , Broussard Cédric , Guillonneau François , Boulé Jean-Baptiste , Delagoutte Emmanuelle 
Published: November 2019

AbstractDNA hemicatenanes (HCs) are DNA structures in which one strand of a double stranded helix passes through the two strands of another double stranded DNA. Frequently mentioned as DNA replication, recombination and repair intermediates, they have been proposed to participate in the spatial organization of chromosomes and in the regulation of gene expression. To explore potential roles of HCs in genome metabolism, proteins capable of binding specifically HCs were purified by fractionating nuclear extracts from Hela cells. This approach identified three RNA-binding proteins: the Tudor-Staphylococcal Nuclease Domain 1 (SND1) protein and two proteins from the Drosophila behavior human splicing family, the ParaSpeckle Protein Component 1 and the Splicing Factor Proline- and Glutamine- rich protein. Since these proteins were partially pure after fractionation, truncated forms of these proteins were expressed in E. coli and purified to near homogeneity. The specificity of their interaction with HCs was re-examined in vitro. The two truncated purified SND1 proteins exhibited a high specificity for HCs, suggesting a role of SND1 protein in targeting the basic transcription machinery to HC structures.
cando.py: Open source software for predictive bioanalytics of large scale drug-protein-disease data
Authors: Mangione William , Falls Zackary , Chopra Gaurav , Samudrala Ram 
Published: November 2019

AbstractElucidating drug-protein interactions is essential for understanding the beneficial effects of small molecule therapeutics in human disease states. Traditional drug discovery methods focus on optimizing the efficacy of a drug against a single biological target of interest. However, evidence supports the multitarget theory, i.e., drugs work by exerting their therapeutic effects via interaction with multiple biological targets. Analyzing drug interactions with a library of proteins provides further insight into disease systems while also allowing for prediction of putative therapeutics against specific indications. We present a Python package for analysis of drug-proteome and drug-disease relationships implementing the Computational Analysis of Novel Drug Opportunities (CANDO) platform [1–7]. The CANDO package allows for rapid drug similarity assessment, most notably via the bioinformatic docking protocol where billions of drug-protein interactions are rapidly scored and the similarity of drug-proteome interaction signatures is calculated. The package also implements a variety of bench-marking protocols to determine how well drugs are related to each other in terms of the indications/diseases for which they are approved. Drug predictions are generated through consensus scoring of the most similar compounds to drugs known to treat a particular indication. Support for comparing and ranking novel chemical entities, as well as machine learning modules for both benchmarking and putative drug candidate prediction is also available. The CANDO Python package is available on GitHub at https://github.com/ram-compbio/CANDO, through the Conda Python package installer, and at http://compbio.org/software/.
Leishmania infection induces a limited differential gene expression in the sand fly midgut
Authors: Coutinho-Abreu Iliano V. , Serafim Tiago D. , Meneses Claudio , Kamhawi Shaden , Oliveira Fabiano , Valenzuela Jesus G. 
Published: November 2019

AbstractBackgroundPhlebotomine sand flies are the vectors of Leishmania worldwide. To develop in the sand fly midgut, Leishmania multiplies and undergoes multiple stage differentiations leading to the infective form, the metacyclic promastigotes. To gain a better understanding of the influence of Leishmania infection in midgut gene expression, we performed RNA-Seq comparing uninfected Lutzomyia longipalpis midguts and Leishmania infantum-infected Lutzomyia longipalpis midguts at seven time points which cover the various developmental Leishmania stages including early time points when blood digestion is taking place and late time points when the parasites are undergoing metacyclogenesis.ResultsOut of over 13,841 transcripts assembled de novo, only 113 sand fly transcripts, about 1%, were differentially expressed. Further, we observed a low overlap of differentially expressed sand fly transcripts across different time points suggesting a specific influence of each Leishmania stage on midgut gene expression. Two main patterns of sand fly gene expression modulation were noticed. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> −32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 4 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by small fold changes (< 32 fold), and the molecular function of such genes are associated with the metabolism of lipids and detoxification of xenobiotics (P450).ConclusionOverall, it appears that Leishmania modulates sand fly gene expression early on in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points, when modest midgut gene expression changes correlate with a massive amount of parasites in the anterior midgut.
Characterizing changes in land cover and forest fragmentation in Dhorpatan Hunting Reserve of Nepal from multi-temporal Landsat observations (1993-2018)
Authors: Sharma Sandeep , Bista Manjit , Mingshi Li 
Published: November 2019

ABSTRACTRecent centuries have experienced drastic changes in land cover around the world where Himalayan countries like Nepal have undergone changes in the past several decades because of increasing anthropogenic pressure, natural risks and climatic factors. Accordingly, forest fragmentation has also been increasing alarmingly, which is a matter of concern for natural resource management agencies and biodiversity conservation communities. In this study, we assessed land cover change and forest fragmentation trends in Dhorpatan Hunting Reserve of Nepal by implementing landscape fragmentation and recovery process models, and calculating landscape indices based on five-date land cover maps derived from Landsat satellite images from 1993 to 2018. Six land cover types including forest, grass land, barren land, agriculture & built-up, water bodies and snow & glaciers were determined after an intensive field survey. Diverse derived image features were fed to the Support Vector Machines classifier to create land cover maps, followed by a validation procedure using field samples and reference data. Land cover maps showed an increase in forest area from 37.32% (1993) to 39.26% (2018) and snow & glaciers from 1.72% (1993) to 2.15% (2018) while a decrease in grassland area from 38.78% (1993) to 36.41% (2018) and agriculture & built-up area from 2.39% (1993) to 1.80% (2018). Barren land and water body showed negligible changes. The spatial explicit process of forest fragmentation indicated that shrinkage was the most responsible factor of forest loss while expansion was dominant to increment for forest restoration. High dependency of people persists on the reserve for subsistence resources being a cause of forest fragmentation and posing threats to biodiversity. Focus should be made on strategies to decrease the anthropogenic pressure on the reserve. This requires approaches that provide sustainable alternative resources to the local people and innovations that will help them become less reliant on natural resources.
Effect of crocin and naringenin supplementation in cryopreservation medium on post-thawed rooster sperm quality and expression of apoptosis associated genes
Authors: Mehdipour Mahdieh , Kia Hossein Daghigh , Najafi Abouzar 
Published: November 2019

AbstractThe aim of our research was to examine the effects of crocin (0.5 (C0.5), 1 (C1) and 1.5 (C1.5) mM) and naringenin (50 (N50), 100 (N100) and 150 (N150) µM) in cryopreservation extender for freezing rooster semen. Sperm motility, viability, abnormalities, membrane integrity, mitochondrial activity, apoptosis status, lipid peroxidation (LP), GPX, SOD, TAC, the mRNA expression of pro-apoptotic (CASPASE 3) and anti-apoptotic (Bcl-2) genes, fertility and hatchability rate were investigated following freeze-thawing. C1 and N100 resulted in the higher (P < 0.05) total motility and progressive motility in comparison to the control group. C1 and N100 improved viability, membrane integrity and reduced lipid peroxidation. We found much higher values for mitochondria activity with C1 and N100 respect to the control group. The C1 and N100 showed lower percentages of early apoptosis when compared with control group. Also, C1 and N100 had higher TAC when compared with control group. The mRNA expression of BCL-2 in the C1 and N100 group were significantly higher than that of other treatments. The expression of CASPASES 3 was significantly reduced in C1 and N100 group (P < 0.05) when compared to control group. Significantly higher percentage of fertility and hatching rate were observed in C1 and N100 compared to the control group. In conclusion, crocin at 1 mM and naringenin at 100 µM seem to improve the post-thawing rooster semen quality, fertility and could protect the sperm against excessive ROS generation by reducing the pro-apoptotic (CASPASE 3) and increasing anti-apoptotic (Bcl-2) genes.
Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function
Authors: Schmidt Cameron A. , Goldberg Emma J. , Green Tom D. , Karnekar Reema R. , Brault Jeffrey J. , Miller Spencer G. , Amorese Adam J. , Yamaguchi Dean J. , Spangenburg Espen E. , McClung Joseph M. 
Published: November 2019

AbstractStored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute ischemia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct hindlimb muscles that have well characterized differences in energetic efficiency (locomotory-extensor digitorum longus (EDL) and postural-soleus muscles) under conditions of reduced carbohydrate supply. 180 mins of acute ischemia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product - inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Restriction of the available intracellular carbohydrate pool by fasting (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting did cause rapid development of passive tension in both muscle types, which may have implications for optimal timing of reperfusion or administration of precision therapeutics.
Transcriptomic analysis of developing seeds in a wheat mutant RSD32 with reduced seed dormancy
Authors: Rikiishi Kazuhide , Sugimoto Manabu , Maekawa Masahiko 
Published: November 2019

AbstractSeed dormancy, a major factor regulating pre-harvest sprouting, can severely hinder wheat cultivation. Abscisic acid biosynthesis and sensitivity play important roles in the regulation of seed dormancy. Reduced Seed Dormancy 32 (RSD32), a wheat mutant with reduced seed dormancy, is derived from the pre-harvest sprouting tolerant cultivar, Norin61. RSD32 is regulated by a single recessive gene and mutant phenotype expressed in a seed-specific manner. Results of this study show that Norin61 has a low germination index (GI) of whole seeds at 50 days after pollination (DAP) and earlier developmental stages. In RSD32, higher GI of whole seeds was found on DAP40. Dormancy was released by DAP50. Gene expressions in embryos of Norin61 and RSD32 were compared using RNA-seq analysis at the different developmental stages of DAP20, DAP30, and DAP40. Numbers of up-regulated gene in RSD32 are similar in all developmental stages. However, down-regulated genes in RSD32 are more numerous on DAP20 and DAP30 than on DAP40. Homologous genes related to circadian clock regulation and Ca2+ signaling pathway, which have fundamental functions for plant growth and development, are involved in down-regulated genes in RSD32 on DAP20. For central components affecting the circadian clock, genes homologous to CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), which act as morning expressed genes, are expressed at lower levels in RSD32. However, higher expressions of TIMING OF CAB EXPRESSION 1 (TOC1) and PHYTOCLOCK 1 homologues, acting as evening expressed genes, are observed in RSD32. Homologues of Ca2+ signaling pathway related genes are found to be specifically expressed on DAP20 in Norin61. Lower expression is shown in RSD32. These results suggest that RSD32 mutation expresses on DAP20 and earlier seed developmental stages and suggest that circadian clock regulation and Ca2+ signaling pathway are involved in regulating wheat seed dormancy.
Syndecan-3 enhances anabolic bone formation through WNT signalling
Authors: Johnson de Sousa Brito Francesca Manuela , Butcher Andrew , Pisconti Addolorata , Poulet Blandine , Prior Amanda , Charlesworth Gemma , Sperinck Catherine , Scotto di Mase Michele , Bou-Gharios George , van ’t Hof Robert Jurgen , Daroszewska Anna 
Published: November 2019

ABSTRACTOsteoporosis is the most common age-related metabolic bone disorder, which is characterised by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however anabolic therapeutics are few and their use is time-restricted. Here we report that Syndecan-3 (SDC3) increases new bone formation through enhancement of WNT signalling. Young adultSdc3−/−mice have a low bone volume phenotype associated with reduced bone formation, increased bone marrow adipose tissue (BMAT), increased bone fragility and a blunted anabolic bone formation response to mechanical loading. The premature osteoporosis-like phenotype ofSdc3−/−mice is primarily explained by delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast-mediated bone resorption. Mechanistically, SDC3 enhances canonical WNT signalling in osteoblasts through stabilisation of Frizzled 1, making SDC3 an attractive target for novel anabolic drug development.
X-ray crystallographic studies on the hydrogen isotope effects of green fluorescent protein at sub-ångström resolutions
Authors: Tai Yang , Takaba Kiyofumi , Hanazono Yuya , Dao Hoang-Anh , Miki Kunio , Takeda Kazuki 
Published: November 2019

Hydrogen atoms are critical to the nature and properties of proteins, and thus deuteration has the potential to influence protein function. In fact, it has been reported that some deuterated proteins show different physical and chemical properties to their protiated counterparts. Consequently, it is important to investigate protonation states around the active site when using deuterated proteins. Here, hydrogen isotope effects on the S65T/F99S/M153T/V163A variant of green fluorescent protein (GFP), in which the deprotonated B form is dominant at pH 8.5, were investigated. The pH/pD dependence of the absorption and fluorescence spectra indicates that the protonation state of the chromophore is the same in protiated GFP in H2O and protiated GFP in D2O at pH/pD 8.5, while the pK
a of the chromophore became higher in D2O. Indeed, X-ray crystallographic analyses at sub-ångström resolution revealed no apparent changes in the protonation state of the chromophore between the two samples. However, detailed comparisons of the hydrogen OMIT maps revealed that the protonation state of His148 in the vicinity of the chromophore differed between the two samples. This indicates that protonation states around the active site should be carefully adjusted to be the same as those of the protiated protein when neutron crystallographic analyses of proteins are performed.