bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to recover from daily caffeine intake
Authors: Lin Yu-Shiuan , Weibel Janine , Landolt Hans-Peter , Santini Francesco , Garbazza Corrado , Kistler Joshua , Rehm Sophia , Rentsch Katharina , Borgwardt Stefan , Cajochen Christian , Reichert Carolin 
Published: July 2021

AbstractCaffeine elicits widespread effects in the central nervous system and is the most frequently consumed psychostimulant worldwide. First evidence indicates that, during daily intake, the elimination of caffeine may slow down and the primary metabolite, paraxanthine, may accumulate. The neural impact of such adaptions is virtually unexplored. In this report, we leveraged the data of a laboratory study with N= 20 participants and three within-subject conditions: caffeine (150 mg caffeine x 3/day x 10 days), placebo (150 mg mannitol x 3/day x 10 days), and withdrawal (caffeine x 9 days, afterwards placebo x 1 day). Using liquid chromatography–mass spectrometry coupled with tandem mass spectrometry, we determined the course of salivary caffeine and paraxanthine, measured regularly at day 10. We assessed grey matter (GM) intensity and cerebral blood flow (CBF) in the withdrawal condition as compared to their changes in caffeine in our previous report. The results indicate high remaining levels of paraxanthine and of caffeine carried overnight during daily intake, and the levels of paraxanthine remained higher than in placebo during withdrawal. After 36 h of withdrawal, the previously reported caffeine-induced GM reduction was partially mitigated, while CBF was elevated compared to placebo. Our findings unveil that conventional daily caffeine intake does not provide sufficient time to clear up psychoactive compounds and restore cerebral responses, even after 36 hours of abstinence. They also suggest investigating consequences of a paraxanthine accumulation during daily caffeine intake.
Sulfated agarans from red seaweed Gracilaria cornea induce macrophages polarization to an antitumor M1 phenotype
Authors: Teles Felipe Barros , Assef Alexia Nathália Brígido , Andrade Renato Martins , Soares Vitória Virgínia Magalhães , da Silva Alves Antônio Willame , Lima-Júnior Roberto César Pereira , Benevides Norma Maria Barros , Wilke Diego Veras 
Published: July 2021

AbstractMarine seaweeds are a rich source of sulfated polysaccharides with several biological activities, including antitumor effect. Some polysaccharides are also described to activate macrophages (Mϕs) to an antitumor M1-like phenotype. Here, we evaluated the capacity of sulfated galactans (SGs) extracts obtained from three seaweed species, Gracilaria cornea (Gc-E), Gracilaria birdiae (Gb-E), and Solieria filiformis (Sf-E), to activate the Mϕs antitumor M1 phenotype. The nitric oxide production, MHCII, and CD86 (M1 markers) were evaluated to screening the bioactive SGs profile on murine Mϕs (RAW 264.7 cells). The direct SGs antiproliferative effect was tested on melanoma B16-F10 cells. In another experimental setting, B16-F10 cells were incubated with a conditioned medium obtained from Mϕs exposed to SGs. The three SGs tested induced NO release. Sf-E directly inhibited B16-F10 cells proliferation compared with the saline group, but Gc-E and Gb-E failed to inhibit cell proliferation. Notably, a conditioned medium (CM) of Mϕs incubated with Gc-E and Sf-E, but not of Gb-E, inhibited the proliferation of B16-F10 cells. Gc-E also induced TNF-α release and increase of M1 markers such as iNOS, MHCII, and CD86. Therefore, Gc-E activates Mϕs to M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation.
Understanding hydropower impacts on Amazonian wildlife is limited by a lack of robust evidence: results from a systematic review
Authors: dos Santos Eduardo Rodrigues , Michalski Fernanda , Norris Darren 
Published: July 2021

AbstractBackground and Research AimsAlthough hydropower provides energy to fuel economic development across Amazonia, strategies to minimize or mitigate impacts in highly biodiverse Amazonian environments remain unclear. The growing number of operational and planned hydroelectrics requires robust scientific evidence to evaluate impacts of these projects on Amazonian vertebrates. Here we investigated the existing scientific knowledge base documenting impacts of hydropower developments on vertebrates across Brazilian Amazonia.MethodsWe reviewed the scientific literature from 1945 to 2020 published in English, Spanish and Portuguese to assess the temporal and spatial patterns in publications and the types of study design adopted as well as scientific evidence presented.ResultsA total of 24 published articles documented impacts on fish (n = 20), mammals (n = 3) and freshwater turtles (n = 1). Most study designs (87.5%) lacked appropriate controls and only three studies adopted more robust Before-After-Control-Impact designs. The published evidence did not generally support causal inference with only two studies (8.3%) including appropriate controls and/or confounding variables.ConclusionDecades of published assessments (54.2% of which were funded by hydropower developers or their subsidiaries) do not appear to have established robust evidence of impacts of hydropower developments on Amazonian vertebrates. This lack of robust evidence could limit the development of effective minimization and mitigation actions for the diverse vertebrate groups impacted by hydroelectrics across Brazilian Amazonia.Implications for ConservationTo avoid misleading inferences there is a need to integrate more robust study designs into impact assessments of hydropower developments in the Brazilian Amazon.
The Effect of a Fennel Extract on the STAT Signaling and Intestinal Barrier Function
Authors: Rabalais John , Kozan Philip , Lu Tina , Durali Nassim , Okamoto Kevin , Das Barun , McGeough Matthew D. , Lee Jae Beom , Barrett Kim E. , Marchelletta Ronald , Sivagnanam Mamata 
Published: July 2021

AbstractBackgroundFoeniculum vulgare,F. vulgare, commonly known as fennel, is believed to be one of the world’s oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties.F. vulgareis used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD).MethodsThis study investigated the effects ofF. vulgareon the barrier function of the intestinal epithelium Signal Transducer and Activator of Transcription (STAT) pathway, which is active in inflammatory bowel disease.To study the protective effects ofF. vulgareextractin vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-γ) and monitored with and withoutF. vulgareextract. To complement ourin vitrostudies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect ofF. vulgareextract can be recapitulatedin vivo.ResultsF. vulgareextract was shown to exert a protective effect on TEER in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated withF. vulgareshowed significantly lower ulcer indices than control mice.ConclusionsWe conclude barrier function of the gastrointestinal tract is improved byF. vulgare, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD.
Environmental transmission of Pseudogymnoascus destructans to hibernating little brown bats
Authors: Hicks Alan C. , Darling Scott , Flewelling Joel , von Linden Ryan , Meteyer Carol U. , Redell Dave , White J. Paul , Redell Jennifer , Smith Ryan , Blehert David , Rayman Noelle , Hoyt Joseph R. , Okoniewski Joseph C. , Langwig Kate E. 
Published: July 2021

ABSTRACTPathogens with persistent environmental stages can have devastating effects on wildlife communities. White-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has caused widespread declines in bat populations of North America. In 2009, during the early stages of the WNS investigation and before molecular techniques had been developed to readily detect P. destructans in environmental samples, we initiated this study to assess whether P. destructans can persist in the hibernaculum environment in the absence of its conclusive bat host and cause infections in naive bats. We transferred little brown bats (Myotis lucifugus) from an unaffected winter colony in northwest Wisconsin to two P. destructans contaminated hibernacula in Vermont where native bats had been excluded. Infection with P. destructans was apparent on some bats within 8 weeks following the introduction of unexposed bats to these environments, and mortality from WNS was confirmed by histopathology at both sites 14 weeks following introduction. These results indicate that environmental exposure to P. destructans is sufficient to cause the infection and mortality associated with WNS in naive bats, which increases the probability of winter colony extirpation and complicates conservation efforts.
Amino acid and nucleotide metabolism shape the selection of trophic levels in animals
Authors: Yu Rosemary , Wang Hao , Nielsen Jens 
Published: July 2021

AbstractWhat an animal eats determines its trophic level (TL) in the food web. The diet of high-TL animals is thought to contain more energy because it contains higher levels of lipids. This however has not been systematically examined in the context of comprehensive metabolic networks of different animals. Here, we reconstruct species-specific genome-scale metabolic models (GEMs) of 32 animals, and calculate the maximum ATP production per unit of food for each animal. Surprisingly, we find that ATP production is closely associated with metabolic flux through central carbon metabolism and amino acid metabolism, while correlation with lipid metabolism is low. Further, metabolism of specific amino acids and nucleotides underlie maximum ATP production from food. Our analyses indicate that amino acid and nucleotide metabolism, rather than lipid metabolism, are major contributors to the selection of animal trophic levels, demonstrating that species-level metabolic flux plays key roles in trophic interactions and evolution.
Effects of warming winter embryo incubation temperatures on larval cisco (Coregonus artedi) survival, growth, and critical thermal maximum
Authors: Stewart Taylor R. , Vinson Mark R. , Stockwell Jason D. 
Published: July 2021

AbstractFreshwater whitefishes, Salmonidae Coregoninae, are cold stenothermic fishes of ecological and socio-economic importance in northern hemisphere lakes that are warming in response to climate change. To address the effect of warming waters on coregonine reproduction we experimentally evaluated different embryo incubation temperatures on post-hatching survival, growth, and critical thermal maximum of larval cisco (Coregonus artedi) sampled from lakes Superior and Ontario. Embryos were incubated at water temperatures of 2.0, 4.4, 6.9, and 8.9°C to simulate present and increased winter temperatures, and hatched larvae were reared in a common environment. For both populations, larval survival and critical thermal maximum were negatively related to incubation temperature, and larval growth was positively related to incubation temperature. The magnitude of change across incubation temperatures was greater in the population sampled from Lake Superior than Lake Ontario for all traits examined. The more rapid decrease in survival and critical thermal maximum across incubation temperatures for larval cisco in Lake Superior, compared to those from Lake Ontario, suggests that Lake Superior larvae may possess a more limited ability to acclimate to and cope with increasing winter water temperatures. However, the rapid increase in growth rates across incubation temperatures in Lake Superior larvae suggests they could recover better from hatching at a small length induced by warm winters, as compared to Lake Ontario larvae. Our results suggest propagation and restoration programs may want to consider integrating natural habitat preferences and maximizing phenotypic variability to ensure offspring are set up for success upon stocking.
Regulatory small RNA, Qrr2, is expressed independently of sigma factor-54 and functions autonomously inVibrio parahaemolyticusto control quorum sensing
Authors: Tague J.G. , Hong J. , Kalburge S.S. , Boyd E.F. 
Published: July 2021

AbstractBacterial cells alter gene expression in response to changes in population density in a process called quorum sensing (QS). InVibrio harveyi, LuxO, a low cell density activator of sigma factor-54 (RpoN), is required for transcription of five non-coding regulatory sRNAs, Qrr1-Qrr5, which each repress translation of the master QS regulator LuxR.Vibrio parahaemolyticus, the leading cause of bacterial seafood-borne gastroenteritis, also contains five Qrr sRNAs that control OpaR (the LuxR homolog), required for capsule polysaccharide (CPS) and biofilm production, motility, and metabolism. We show that in a ΔluxOdeletion mutant,opaRwas de-repressed and CPS and biofilm were produced. However, in a ΔrpoNmutant,opaRwas repressed, no CPS was produced, and less biofilm production was observed compared to wild type. To determine whyopaRwas repressed, expression analysis in ΔluxOshowed all fiveqrrgenes were repressed, while in ΔrpoNtheqrr2gene was significantly de-repressed. Reporter assays and mutant analysis showed Qrr2 sRNA can act autonomously to control OpaR. Bioinformatics analysis identified a sigma-70 (RpoD) -35 -10 promoter overlapping the canonical sigma-54 (RpoN) promoter in theqrr2regulatory region. Mutagenesis of the sigma-70 -10 promoter site in the ΔrpoNmutant background, resulted in repression ofqrr2.Analysis ofqrrquadruple deletion mutants, in which only a singleqrrgene is present, showed that only Qrr2 sRNA can act autonomously to regulateopaR. Mutant and expression data also demonstrated that RpoN and the global regulator Fis act additively to repressqrr2. Our data has uncovered a new mechanism ofqrrexpression and shows that Qrr2 sRNA is sufficient for OpaR regulation.ImportanceThe quorum sensing non-coding sRNAs are present in allVibriospecies but vary in number and regulatory roles among species. In the Harveyi clade, all species contain fiveqrrgenes that, inV. harveyi, are additive in function to control LuxR. In the Cholerae clade, fourqrrgenes are present, and inV. choleraetheqrrgenes are redundant in function to control HapR (the LuxR homolog). Here, we show that inV. parahaemolyticus, onlyqrr2can function autonomously to control OpaR, and it is controlled by two overlapping promoters. Theqrr2sigma-70 promoter is present in all strains ofV. parahaemolyticusand in other members of the Harveyi clade suggesting a conserved mechanism of regulation.
Extracellular ribosomal RNA provides a window into taxon-specific microbial lysis
Authors: Zhong Kevin Xu , Wirth Jennifer F. , Chan Amy M. , Suttle Curtis A. 
Published: July 2021

AbstractMicrobes are by far the dominant biomass in the world’s oceans and drive biogeochemical cycles that are critical to life on Earth. The composition of marine microbial communities is highly dynamic spatially and temporally, with consequent effects on their functional roles. In part, these changes in composition result from viral lysis, which is taxon-specific and estimated to account for about half of marine microbial mortality. Here we determined taxon-specific cell lysis of prokaryotes in coastal seawater by sequencing extracellular and cellular ribosomal RNA (rRNA). We detected lysis in about 15% of the 16946 prokaryotic amplicon sequence variants (ASVs) identified, and lysis of up to 34% of the ASVs within a water sample. High lysis was most commonly associated with rare but typically highly productive bacteria, while relatively low lysis was more common in taxa that are often abundant, consistent with the proposed model of “kill the winner”, and the idea that less abundant taxa generally experience higher relative lysis than dominant taxa. These results provide an explanation to the long-standing conundrum of why highly productive bacteria that are readily isolated from seawater are often in very low abundance.One Sentence SummaryExtracellular rRNA shows wide variation in cell lysis among prokaryotic taxa.
ionbot: a novel, innovative and sensitive machine learning approach to LC-MS/MS peptide identification
Authors: Degroeve Sven , Gabriels Ralf , Velghe Kevin , Bouwmeester Robbin , Tichshenko Natalia , Martens Lennart 
Published: July 2021

AbstractMass spectrometry-based proteomics generates vast amounts of signal data that require computational interpretation to obtain peptide identifications. Dozens of algorithms for this task exist, but all exploit only part of the acquired data to judge a peptide-to-spectrum match (PSM), ignoring important information such as the observed retention time and fragment ion peak intensity pattern. Moreover, only few identification algorithms allow open modification searches that can substantially increase peptide identifications.We here therefore introduce ionbot, a novel open modification search engine that is the first to fully merge machine learning with peptide identification. This core innovation brings the ability to include a much larger range of experimental data into PSM scoring, and even to adapt this scoring to the specifics of the data itself. As a result, ionbot substantially increases PSM confidence for open searches, and even enables a further increase in peptide identification rate of up to 12% by also considering lower-ranked, co-eluting matches for a fragmentation spectrum. Moreover, the exclusive use of machine learning for scoring also means that any future improvements to predictive models for peptide behavior will also result in more sensitive and accurate peptide identification.
Gradient-mixing LEGO robots for purifying DNA origami nanostructures of multiple components by rate-zonal centrifugation
Authors: Sentosa Jason , Horne Brian , Djutanta Franky , Showkeir Dominic , Rezvani Robert , Hariadi Rizal F. 
Published: July 2021

AbstractDNA origami purification is critical in emerging applications of functionalized DNA nanostructures from basic fundamental biophysics, nanorobots to therapeutics. Advances in DNA origami purification have led to the establishment of rate-zonal centrifugation (RZC) as a scalable, high-yield, and contamination-free approach to purifying DNA origami nanostructures. In RZC purification, a linear density gradient is created using viscous agents, such as glycerol and sucrose, to separate molecules based on their mass and shape during high-rpm centrifugation. However, current methods for creating density gradients are typically time-consuming because of their reliance on slow passive diffusion. Here, we built a LEGO gradient mixer to rapidly create a quasi-continuous density gradient with minimal layering of concentrations using simple rotational motion. We found that rotating two layers of different concentrations at an angle can reduce the diffusion time from a few hours to mere minutes. The instrument needed to perform the movement can be constructed from low-cost components, such as Arduino and LEGO Mindstorms pieces, and has comparable efficacy to commercial gradient mixers currently available. Our results demonstrate that the creation of a linear density gradient can be achieved with minimal labor, time, and cost with this machine. With the recent advances in DNA origami production, we anticipate our findings to further improve the viability of scaling up DNA origami purification in grams quantities. Our simple process enables automated large-scale purification of functionalized DNA origami more feasible in resource-constrained settings.
Behavioral and fMRI evidence that arousal enhances bottom-up attention and memory selectivity in young but not older adults
Authors: Gallant Sara N. , Kennedy Briana L. , Bachman Shelby L. , Huang Ringo , Lee Tae-Ho , Mather Mara 
Published: July 2021

AbstractDuring a challenge or emotional experience, increases in arousal help us focus on the most salient or relevant details and ignore distracting stimuli. The noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate this adaptive attentional selectivity. However, age-related changes in the noradrenergic system and attention networks in the brain may reduce the efficiency of arousal to modulate selective processing in older adults. In the current neuroimaging study, we examined age differences in how arousal affects bottom-up attention to category-selective stimuli differing in perceptual salience. We found a dissociation in how arousal modulates selective processing in the young and older brain. In young adults, emotionally arousing sounds enhanced selective incidental memory and brain activity in the extrastriate body area for salient versus non-salient images of bodies. Older adults showed no such advantage in selective processing under arousal. These age differences could not be attributed to changes in the arousal response or less neural distinctiveness in old age. Rather, our results suggest that, relative to young adults, older adults become less effective at focusing on salient over non-salient details during increases in emotional arousal.
Differential impact of TNFRSF co-stimulation on CD8+T cell cytokine production by feedback control of surface receptor expression
Authors: Nguyen John , Pettmann Johannes , Kruger Philipp , Dushek Omer 
Published: July 2021

AbstractT cell responses towards infections and cancers are regulated by a host of co-signalling receptors that are largely grouped into the binary categories of co-stimulation and co-inhibition. The TNF receptor superfamily (TNFRSF) members 4-1BB, CD27, GITR, and OX40 are well-established co-stimulation receptors with largely shared molecular pathways raising the question of whether they also have a similar impact on quantitative T cell responses, such as the efficacy, sensitivity, and duration of T cell responses. Here, we systematically stimulated primary human CD8+T cell blasts with dose ranges of antigen and ligands for TNFRSF members to screen for their quantitative effects on cytokine production. Although both 4-1BB and CD27 increased efficacy, only 4-1BB was able to prolong the duration of cytokine production, and both had only a modest impact on antigen sensitivity. An operational model could explain these divergent quantitative phenotypes using a shared signalling mechanism based on the surface expression of 4-1BB, but not CD27, being regulated through a signalling feedback. The model predicted that CD27 co-stimulation would increase 4-1BB expression and subsequent 4-1BB co-stimulation, which we confirmed experimentally. Although GITR and OX40 produced only minor changes in cytokine production on their own, we found that like 4-1BB, CD27 could enhance GITR expression and subsequent GITR co-stimulation. Thus, feedback control of induced TNFRSF surface expression explains both synergy and differential impact on cytokine production. The work highlights that different co-stimulation receptors can have different quantitative phenotypes on the same output allowing for highly regulated control of T cell responses.