bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Human Mitochondrial DNA Content by Southern Blotting and Nonradioactive Probe Hybridization
Authors: Wheeler Joel H. , Young Carolyn K. J. , Young Matthew J. 
Published: April 2019

AbstractA single cell can contain several thousand copies of the mitochondrial DNA genome or mtDNA. Tools for assessing mtDNA content are necessary for clinical and toxicological research, as mtDNA depletion is linked to genetic disease and drug toxicity. For instance, mtDNA depletion syndromes are typically fatal childhood disorders that are characterized by severe declines in mtDNA content in affected tissues. Mitochondrial toxicity and mtDNA depletion have also been reported in human immunodeficiency virus–infected patients treated with certain nucleoside reverse transcriptase inhibitors. Further, cell culture studies have demonstrated that exposure to oxidative stress stimulates mtDNA degradation. Here we outline a Southern blot and nonradioactive digoxigenin‐labeled probe hybridization method to estimate mtDNA content in human genomic DNA samples. © 2019 by John Wiley & Sons, Inc.
Effect of Strontium Ions on Crystallization of Amorphous Calcium Carbonate
Authors: Schmidt Ingo , Zolotoyabko Emil , Lee Kyubock , Gjardy André , Berner Alex , Lakin Evgeny , Fratzl Peter , Wagermaier Wolfgang 
Published: April 2019

AbstractIn biomineralization, amorphous precursors enable formation of complicated crystal shapes and incorporation of organic and inorganic impurities. In some cases the concentrations of the inorganic impurity atoms greatly exceed the thermodynamical (equilibrium) solubility limits. To shed additional light on this, crystallization experiments with Sr‐rich amorphous calcium carbonate (ACC) are carried out. The Sr‐concentration in ACC, Sr/(Ca+Sr) ≈0.3, is more than 60 times larger than its solubility limit in calcite. Crystallization of ACC is accomplished using two different pathways: i) in a high humidity environment at room temperature, and ii) upon heating at 300 °C. In both cases, X‐ray diffraction measurements revealed the formation of particular crystal phases with an ability to take up substantial amounts of Sr. Crystals formed via the humidity route comprised spatially separated regions of almost pure rhombohedral calcite and orthorhombic aragonite/strontianite solid solution with a Sr/(Ca+Sr) ratio equal nearly 0.5. Crystallization of ACC upon heating resulted in the appearance of a new calcite‐like phase with reduced space symmetry, , instead of for regular calcite. Symmetry reduction in this Sr‐rich ‐phase is due to the rotational disorder of flat carbonate groups about the c‐axis, which is responsible for the enhanced lattice capacity of Sr incorporation.
A Multiphase Protocol for Selective Hydrogenation and Reductive Amination of Levulinic Acid with Integrated Catalyst Recovery
Authors: Bellè Alessandro , Tabanelli Tommaso , Fiorani Giulia , Perosa Alvise , Cavani Fabrizio , Selva Maurizio 
Published: April 2019

AbstractAt 60–150 °C and 15–35 bar H2, two model reactions of levulinic acid (LA), hydrogenation and reductive amination with cyclohexylamine, were explored in a multiphase system composed of an aqueous solution of reactants, a hydrocarbon, and commercial 5 % Ru/C as a heterogeneous catalyst. By tuning the relative volume of the immiscible water/hydrocarbon phases and the concentration of the aqueous solution, a quantitative conversion of LA was achieved with formation of γ‐valerolactone orN‐(cyclohexylmethyl)pyrrolidone in >95 and 88 % selectivity, respectively. Additionally, the catalyst could be segregated in the hydrocarbon phase and recycled in an effective semi‐continuous protocol. Under such conditions, formic acid additive affected the reactivity of LA through a competitive adsorption on the catalyst surface. This effect was crucial to improve selectivity for the reductive amination process. The comparison of 5 % Ru/C with a series of carbon supports demonstrated that the segregation phenomenon in the hydrocarbon phase, never previously reported, was pH‐dependent and effective for samples displaying a moderate surface acidity.
GNrep mouse: A reporter mouse for front–rear cell polarity
Authors: Barbacena Pedro , Ouarné Marie , Haigh Jody J. , Vasconcelos Francisca F. , Pezzarossa Anna , Franco Claudio A. 
Published: April 2019

SummaryCell migration is essential during development, regeneration, homeostasis, and disease. Depending on the microenvironment, cells use different mechanisms to migrate. Yet, all modes of migration require the establishment of an intracellular front–rear polarity axis for directional movement. Although front–rear polarity can be easily identified in in vitro conditions, its assessment in vivo by live‐imaging is challenging due to tissue complexity and lack of reliable markers. Here, we describe a novel and unique double fluorescent reporter mouse line to study front–rear cell polarity in living tissues, called GNrep. This mouse line simultaneously labels Golgi complexes and nuclei allowing the assignment of a nucleus‐to‐Golgi axis to each cell, which functions as a readout for cell front–rear polarity. As a proof‐of‐principle, we validated the efficiency of the GNrep line using an endothelial‐specific Cre mouse line. We show that the GNrep labels the nucleus and the Golgi apparatus of endothelial cells with very high efficiency and high specificity. Importantly, the features of fluorescent intensity and localization for both mCherry and eGFP fluorescent intensity and localization allow automated segmentation and assignment of polarity vectors in complex tissues, making GNrep a great tool to study cell behavior in large‐scale automated analyses. Altogether, the GNrep mouse line, in combination with different Cre recombinase lines, is a novel and unique tool to study of front–rear polarity in mice, both in fixed tissues or in intravital live imaging. This new line will be instrumental to understand cell migration and polarity in development, homeostasis, and disease.
Sequestration and biosynthesis of cyanogenic glucosides in passion vine butterflies and consequences for the diversification of their host plants
Authors: Pinheiro de Castro Érika C. , Zagrobelny Mika , Zurano Juan Pablo , Zikan Cardoso Márcio , Feyereisen René , Bak Søren 
Published: April 2019

AbstractThe colorful heliconiine butterflies are distasteful to predators due to their content of defense compounds called cyanogenic glucosides (CNglcs), which they biosynthesize from aliphatic amino acids. Heliconiine larvae feed exclusively on Passiflora plants where ~30 kinds of CNglcs have been reported. Among them, some CNglcs derived from cyclopentenyl glycine can be sequestered by some Heliconius species. In order to understand the evolution of biosynthesis and sequestration of CNglcs in these butterflies and its consequences for their arms race with Passiflora plants, we analyzed the CNglc distribution in selected heliconiine and Passiflora species. Sequestration of cyclopentenyl CNglcs is not an exclusive trait of Heliconius, since these compounds were present in other heliconiines such as Philaethria, Dryas and Agraulis, and in more distantly related genera Cethosia and Euptoieta. Thus, it is likely that the ability to sequester cyclopentenyl CNglcs arose in an ancestor of the Heliconiinae subfamily. Biosynthesis of aliphatic CNglcs is widespread in these butterflies, although some species from the sara‐sapho group seem to have lost this ability. The CNglc distribution within Passiflora suggests that they might have diversified their cyanogenic profile to escape heliconiine herbivory. This systematic analysis improves our understanding on the evolution of cyanogenesis in the heliconiine–Passiflora system.
Embolism recovery strategies and nocturnal water loss across species influenced by biogeographic origin
Authors: Zeppel Melanie J. B. , Anderegg William R. L. , Adams Henry D. , Hudson Patrick , Cook Alicia , Rumman Rizwana , Eamus Derek , Tissue David T. , Pacala Stephen W. 
Published: April 2019

AbstractDrought‐induced tree mortality is expected to increase in future climates with the potential for significant consequences to global carbon, water, and energy cycles. Xylem embolism can accumulate to lethal levels during drought, but species that can refill embolized xylem and recover hydraulic function may be able to avoid mortality. Yet the potential controls of embolism recovery, including cross‐biome patterns and plant traits such as nonstructural carbohydrates (NSCs), hydraulic traits, and nocturnal stomatal conductance, are unknown. We exposed eight plant species, originating from mesic (tropical and temperate) and semi‐arid environments, to drought under ambient and elevated CO2 levels, and assessed recovery from embolism following rewatering. We found a positive association between xylem recovery and NSCs, and, surprisingly, a positive relationship between xylem recovery and nocturnal stomatal conductance. Arid‐zone species exhibited greater embolism recovery than mesic zone species. Our results indicate that nighttime stomatal conductance often assumed to be a wasteful use of water, may in fact be a key part of plant drought responses, and contribute to drought survival. Findings suggested distinct biome‐specific responses that partially depended on species climate‐of‐origin precipitation or aridity index, which allowed some species to recover from xylem embolism. These findings provide improved understanding required to predict the response of diverse plant communities to drought. Our results provide a framework for predicting future vegetation shifts in response to climate change.
Life history strategies drive size‐dependent biomass allocation patterns of dryland ephemerals and shrubs
Authors: Chen Renfei , Ran Jinzhi , Huang Heng , Dong Longwei , Sun Yuan , Ji Mingfei , Hu Weigang , Yao Shuran , Lu Jingli , Gong Haiyang , Xie Shubin , Du Qiajun , Hou Qingqing , Niklas Karl J. , Deng Jianming 
Published: April 2019

AbstractPlant biomass allocation patterns are important to understanding and predicting ecosystem carbon cycles and other important ecological processes. Consequently, many attempts have been made to study these patterns. However, most studies focus on data from species in temperate forests to the neglect of data from desert species adapted to arid conditions. We hypothesize that different life history strategies drive or at least participate in different plant biomass allocation patterns, as, for example, the life history differences between desert ephemeral and shrub species. We tested this hypothesis using field data gathered directly from the entire desert vegetation in Northwestern China. When the data from each of the two species groups are pooled, ephemeral and shrub species manifest different scaling relationships between above‐ and belowground biomass, unlike the isometric scaling relationships typically reported for forest tree species. The observed scaling relationships are sensitive to water stress and temperature gradients. The scaling exponents numerically decrease with increasing drought stress, and relatively more biomass is allocated to shoot growth in ephemeral species (presumably to rapidly complete their life history). In the case of shrubs, the numerical value of the scaling exponent is insensitive to rainfall, presumably because these species allocate more biomass to root growth to access belowground water. However, the scaling exponent is significantly sensitive to temperature, which also regulates root growth. Moreover, for the two species groups, root–shoot ratios are jointly regulated by precipitation and temperature. The different biomass allocation patterns appear to result from different life histories that maximize either competition among neighboring plants, or escaping damage from drought and low temperatures. These findings show how overall body size and life histories jointly regulate biomass allocation patterns under different extreme conditions and provide insights into estimating the dry carbon content in dryland ecosystems.
Downstream transport and seasonal variation in freshwater pearl mussel (Margaritifera margaritifera) eDNA concentration
Authors: Wacker Sebastian , Fossøy Frode , Larsen Bjørn Mejdell , Brandsegg Hege , Sivertsgård Rolf , Karlsson Sten 
Published: April 2019

AbstractEnvironmental DNA (eDNA) can be used to detect the presence and abundance of aquatic organisms from water samples. Before implementing this methodology as a tool for monitoring, more knowledge is needed on variation in eDNA concentrations in relation to species abundance and potential confounding factors. Shedding and decay of eDNA may vary extensively over the season and are dependent on environmental factors such as water temperature and on biological processes such as activity level and reproduction. In lotic systems, eDNA concentrations are also affected by downstream transport of eDNA. Sessile freshwater mussels provide an ideal study system for investigating the relationship between species spatial distribution and eDNA concentrations in lotic systems. We quantified freshwater pearl mussel (Margaritifera margaritifera) eDNA concentrations at four localities in a natural river with detailed knowledge of mussel spatial distribution: (a) upstream of the known species distribution, just downstream (b) a small and (c) a large aggregation and (d) 1,700 m downstream of the large aggregation. To study seasonal variation, we quantified eDNA concentrations during three periods: (a) in late spring, with cold water and relatively inactive mussels; (b) in mid‐summer, with higher water temperature and active mussel filtration; and (c) in late summer, during the release of larvae. Species detection was highly reliable, with no detection of eDNA upstream of the species distribution and complete detection downstream of the large aggregation. Detection success of the small aggregation was low, with 13% of the samples testing positive. Downstream transport was efficient, with no significant decrease in eDNA concentrations over 1,700 m river distance. Seasonal variation was strong, with a 20‐fold increase in eDNA concentrations from late spring to late summer, during reproduction. Our results highlight both the potential and challenges of eDNA monitoring in lotic systems.
Regulation of gamma‐frequency oscillation by feedforward inhibition: A computational modeling study
Authors: Rennó‐Costa César , Teixeira Daniel Garcia , Soltesz Ivan 
Published: April 2019

AbstractThroughout the brain, reciprocally connected excitatory and inhibitory neurons interact to produce gamma‐frequency oscillations. The emergent gamma rhythm synchronizes local neural activity and helps to select which cells should fire in each cycle. We previously found that such excitation‐inhibition microcircuits, however, have a potentially significant caveat: the frequency of the gamma oscillation and the level of selection (i.e., the percentage of cells that are allowed to fire) vary with the magnitude of the input signal. In networks with varying levels of brain activity, such a feature may produce undesirable instability on the time and spatial structure of the neural signal with a potential for adversely impacting important neural processing mechanisms. Here we propose that feedforward inhibition solves the latter instability problem of the excitation‐inhibition microcircuit. Using computer simulations, we show that the feedforward inhibitory signal reduces the dependence of both the frequency of population oscillation and the level of selection on the magnitude of the input excitation. Such a mechanism can produce stable gamma oscillations with its frequency determined only by the properties of the feedforward network, as observed in the hippocampus. As feedforward and feedback inhibition motifs commonly appear together in the brain, we hypothesize that their interaction underlies a robust implementation of general computational principles of neural processing involved in several cognitive tasks, including the formation of cell assemblies and the routing of information between brain areas.
Pharmacokinetic Drug‐Drug Interactions Between Letermovir and the Immunosuppressants Cyclosporine, Tacrolimus, Sirolimus, and Mycophenolate Mofetil
Authors: McCrea Jacqueline B. , Macha Sreeraj , Adedoyin Adedayo , Marshall William , Menzel Karsten , Cho Carolyn R. , Liu Fang , Zhao Tian , Levine Vanessa , Kraft Walter K. , Yoon Esther , Panebianco Deborah , Stoch S. Aubrey , Iwamoto Marian 
Published: April 2019

AbstractLetermovir (AIC246, MK‐8228) is a human cytomegalovirus terminase inhibitor indicated for the prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant recipients that is also being investigated for use in other transplant settings. Many transplant patients receive immunosuppressant drugs, of which several have narrow therapeutic ranges. There is a potential for the coadministration of letermovir with these agents, and any potential effect on their pharmacokinetics (PK) must be understood. Five phase 1 trials were conducted in 73 healthy female participants to evaluate the effect of letermovir on the PK of cyclosporine, tacrolimus, sirolimus, and mycophenolic acid (active metabolite of mycophenolate mofetil [MMF]), as well as the effect of cyclosporine and MMF on letermovir PK. Safety and tolerability were also assessed. Coadministration of letermovir with cyclosporine, tacrolimus, and sirolimus resulted in 1.7‐, 2.4‐, and 3.4‐fold increases in area under the plasma concentration–time curve and 1.1‐, 1.6‐, and 2.8‐fold increases in maximum plasma concentration, respectively, of the immunosuppressants. Coadministration of letermovir and MMF had no meaningful effect on the PK of mycophenolic acid. Coadministration with cyclosporine increased letermovir area under the plasma concentration–time curve by 2.1‐fold and maximum plasma concentration by 1.5‐fold, while coadministration with MMF did not meaningfully affect the PK of letermovir. Given the increased exposures of cyclosporine, tacrolimus, and sirolimus, frequent monitoring of concentrations should be performed during administration and at discontinuation of letermovir, with dose adjustment as needed. These data support the reduction in clinical dosage of letermovir (to 240 mg) upon coadministration with cyclosporine.
A STING to inflammation and autoimmunity
Authors: Kumar Vijay 
Published: April 2019

Abstract
Various intracellular pattern recognition receptors (PRRs) recognize cytosolic pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Cyclic GMP-AMP synthase (cGAS), a cytosolic PRR, recognizes cytosolic nucleic acids including dsDNAs. The recognition of dsDNA by cGAS generates cyclic GMP-AMP (GAMP). The cGAMP is then recognized by STING generating type 1 IFNs and NF-κB-mediated generation of pro-inflammatory cytokines and molecules. Thus, cGAS-STING signaling mediated recognition of cytosolic dsDNA causing the induction of type 1 IFNs plays a crucial role in innate immunity against cytosolic pathogens, PAMPs, and DAMPs. The overactivation of this system may lead to the development of autoinflammation and autoimmune diseases. The article opens with the introduction of different PRRs involved in the intracellular recognition of dsDNA and gives a brief introduction of cGAS-STING signaling. The second section briefly describes cGAS as intracellular PRR required to recognize intracellular nucleic acids (dsDNA and CDNs) and the formation of cGAMP. The cGAMP acts as a second messenger to activate STING- and TANK-binding kinase 1-mediated generation of type 1 IFNs and the activation of NF-κB. The third section of the article describes the role of cGAS-STING signaling in the induction of autoinflammation and various autoimmune diseases. The subsequent fourth section describes both chemical compounds developed and the endogenous negative regulators of cGAS-STING signaling required for its regulation. Therapeutic targeting of cGAS-STING signaling could offer new ways to treat inflammatory and autoimmune diseases.
The Benefits of the Learn to Think Program for Preschoolers’ Creativity: An Explorative Study
Authors: Bai Honghong , Duan Haijun , Kroesbergen Evelyn H. , Leseman Paul P. M. , Hu Weiping 
Published: April 2019

AbstractThis paper presents the Learn to Think preschool (LTT‐P) program for promoting creativity in preschoolers and reviews its potential benefits. LTT‐P was designed within the framework of the successful LTT creativity program for older students and both were developed to fit the Chinese education system. To assess the potential benefits of LTT‐P, a quasi‐experimental pretest‐posttest control group study was conducted in a preschool in an urban region in the northwest of China, involving 68 middle level and 87 senior level children. The Lines and Circles subtests of the Torrance Test of Creative Thinking were used to examine the development of children's creativity on the dimensions fluency, originality, and elaboration between pretest and posttest. The results suggest that the LTT‐P program has the potential to promote young children's creative thinking, especially with regard to the aspects of originality and elaboration. The results for fluency are less clear. To the best of our knowledge, LTT‐P is the first program, grounded in a structured learning theory and sound curriculum framework, to support children's creativity development in Chinese early childhood education.
Fire outbreaks in extreme climate years in the State of Rio de Janeiro, Brazil
Authors: de Andrade Caio F. , Duarte João B. , Barbosa Maria Lucia F. , de Andrade Melina D. , de Oliveira Raquel O. , Delgado Rafael C. , Pereira Marcos G. , Batista Tays S. , Teodoro Paulo E. 
Published: April 2019

AbstractPlant burning in tropical countries is a threat to the environment. It not only damages the local ecology but also affects the economy and society. This work aimed to analyze the meteorological systems, soil attributes, and meteorological variables derived from NCEP‐DOE Reanalysis 2 for 3 years of atypical climatic events (2005, 2010, and 2015); and relate these factors to the occurrence of fire outbreaks in the State of Rio de Janeiro, Brazil. In 2005, a total of 1,085 fire outbreaks were registered in the State, and most of them occurred during the dry season in the soil classes ultisol (542) and oxisol (139). The highest fire outbreaks concentration was reported in 2010, totaling 1, 702 outbreaks, and Argissolo and Latossolo (747 and 301, respectively) were also the most predominant soil classes. This fact can be explained by the greater predominance of pastures and greater area in km2 in the State. In 2015, the highest number of fire outbreaks was recorded, again, in Argissolo (418), in addition to Gleissolo (102). The total number of fire outbreaks registered in 2015 was lower than those recorded in 2005 and 2010, totaling 916 fire outbreaks statewide. The correlation shows maximum positive values of zonal wind component (0.71) for 2005. The highest negative values correlations found for 2005, 2010, and 2015 were for the meteorological traits soil moisture and relative air humidity, respectively. The present study is important for highlighting up the vulnerability of the Atlantic Forest ecosystem, given the occurrence of fire outbreaks.