bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outpatient antibiotic prescribing and demographic factors associated with state-level septicemia mortality rates in US adults
Authors: Goldstein Edward , Lipsitch Marc 
Published: December 2018

AbstractBackgroundRates of septicemia/sepsis mortality and hospitalization in the US have risen significantly during the recent years, and antibiotic use may contribute to those rates through various mechanisms.MethodsWe used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for fluoroquinolones, penicillins, macrolides, and cephalosporins between 2013-2014 to state-specific rates of septicemia mortality (ICD-10 codes A40-41 present as either the underlying or contributing causes of death) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85+y) between 2013-2014, adjusting for median household income, average annual temperature, age-specific percentages of state residents who (i) lived below the poverty level, (ii) were African American, (iii) lacked health insurance (in non-elderly age groups), and random effects associated with the different US Health and Human Services (HHS) regions.ResultsRates of penicillin prescribing were positively associated with septicemia mortality rates in the analyses for persons aged 65-74y, 75-84y and over 85y. Rates of cephalosporin prescribing were positively associated with septicemia mortality rates in the analyses for persons aged 18-49y and 65-74y. Rates of fluoroquinolone prescribing were positively associated with septicemia mortality rates in the analyses for persons aged 18-49y. Percent African Americans in a given age group was positively associated with septicemia mortality rates in the analyses for age groups over 65y, and 18-49y. Percent of residents in a given age group living below the poverty level was positively associated with septicemia mortality rates in the analysis for persons aged 65-74y.ConclusionsOur results suggest that rates of penicillin prescribing are associated with rates of septicemia mortality in older US adults, while rates of cephalosporin prescribing are associated with rates of septicemia mortality in persons aged 18-49y and 65-74y, and rates of fluoroquinolone prescribing are associated with rates of septicemia mortality in persons aged 18-49y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of different syndromes, such as replacement of fluoroquinolones by other antibiotics, possibly penicillins and cephalosporins following the recent US FDA guidelines on restriction of fluoroquinolone use, on the rates of sepsis mortality.
Approximating instantaneous vaccine efficacy from cumulative vaccine efficacy
Authors: Zandvoort Kevin van , Clark Andrew , Jit Mark , Flasche Stefan 
Published: December 2018

AbstractFew methods exist to estimate vaccine efficacy and its decay following immunisation. Existing methods are largely based on survival analyses such as Poisson or Cox-regression, applied to individual-level data from randomised placebo-controlled trials (RCTs), however, such are often not easily available for analysing pooling evidence across trials. Hence, cumulative vaccine efficacy (VE), the commonly reported endpoint, is implicitly assumed a reasonable proxy for the instantaneous vaccine efficacy (iVE). This assumption is violated if the relative risk (RR) of vaccinated vs unvaccinated is not constant over time, i.e. if vaccine efficacy changes after immunisation. We propose a method to overcome this issue. We use estimates of VE stratified by time since completed immunisation, and estimate time-dependent iVE. We validate the method against simulated data for two forms of vaccine protection: all-or-nothing protection and leaky protection. We illustrate how VE estimates are biased by time-dependent effects in the baseline force of infection and in iVE. Our proposed method improves upon available iVE estimation techniques, particularly if the vaccine induced leaky-like protection and the disease outcome is rare.
Functional connectivity of the anterior and posterior hippocampus: differential effects of glucose in younger and older adults
Authors: Peters Riccarda , White David J. , Cornwell Brian R. , Scholey Andrew 
Published: December 2018

Abstract:The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory.Here we probe age, glucose and human cognition with a special emphasis on resting state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design thirty-two healthy adults (16 young and 16 older) ingested a drink containing 25g glucose or placebo across two counterbalanced sessions. They then underwent resting state functional magnetic resonance imaging and cognitive testing. There was a clear dissociation in the effects of glucose by age. In older participants rsFC between posterior hippocampus (pHPC) and medial prefrontal cortex (mPFC) increased after glucose ingestion, whereas in younger participants connectivity decreased. Magnitude change in rsFC from pHPC to mPFC was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants. This study is the first to demonstrate the selective modulation of pHPC connectivity in the acute setting.
Intuitive and broadly applicable definitions of niche and fitness differences
Authors: Spaak Jurg W. , De Laender Frederik 
Published: December 2018

AbstractExplaining nature’s biodiversity is a key challenge for science. To persist, populations must be able to grow faster when rare, a feature called negative frequency dependence and quantified as ‘niche differences’ (𝒩) in coexistence theory. Here, we first show that available definitions of 𝒩 differ in how 𝒩 link to species interactions, are difficult to interpret, and often apply to specific community types only. We then present a new definition of 𝒩 that is intuitive and applicable to a broader set of (modelled and empirical) communities than is currently the case, filling a main gap in the literature. Given 𝒩, we also re-define fitness differences (ℱ) and illustrate how 𝒩 and ℱ determine coexistence. Finally, we demonstrate how to apply our definitions to theoretical models and experimental data, and provide ideas on how they can facilitate comparison and synthesis in community ecology.
First detection and molecular identification of the zoonoticAnaplasma caprain deer in France
Authors: Jouglin Maggy , Blanc Barbara , de la Cotte Nathalie , Ortiz Katia , Malandrin Laurence 
Published: December 2018

AbstractCervids are known to be reservoir of zoonotic tick-transmitted bacteria. The aim of this study was to perform a survey in a wild fauna reserve to characterizeAnaplasmaspecies carried by captive red deer and swamp deer. Blood from 59 red deer and 7 swamp deer was collected and analyzed over a period of two years. A semi-nested PCR that targets the23SrRNA was performed to detect and characteriseAnaplasmaspp. and determine zoonotic species presence.Anaplasma phagocytophilumwas identified in 14/59 deer (23.7%) but not in swamp deer. Few sequences could not be assigned to any particular species based on the23SrRNA sequences. Nested PCR targeting16SrRNA,gltAandgroELgenes and sequencing analysis detected a recently reported zoonotic species,Anaplasma caprain red deer as well as in swamp deer. This is the first reporting of the tick-borne zoonotic bacteriumA. caprain France, a species otherwise described only in China and Japan, in goats, sheep, deer and japanese serows. Even if this bacterium may have been introduced in the Park with infected imported animals, its local epidemiological cycle through tick transmission seems possible as locally born deer were found infected. Diagnostic methods, especially molecular ones, should take into account the potential infection of animals and humans with this species.
Elaborate pupils in skates may help camouflage the eye
Authors: Youn Sean , Okinaka Corey , Mäthger Lydia M 
Published: December 2018

AbstractThe little skateLeucoraja erinaceahas elaborately shaped pupils, whose characteristics and functions have not been studied extensively. It has been suggested that such pupil shapes may camouflage the eye; yet, no experimental evidence has been presented to support this claim. Skates are bottom-dwellers that often bury into the substrate with their eyes protruding. If these pupils serve any camouflage function, we expect there to be a pupillary response related to the spatial frequency (“graininess”) of the background against which the eye is viewed. Here, we tested whether skate pupils dilate or constrict in response to background spatial frequency. We placed skates on background substrates with different spatial frequencies and recorded pupillary responses at three light intensities. In experiment 1, the skates’ pupillary response to three artificial checkerboards of different spatial frequencies was recorded. Skates responded to changing light intensity with pupil dilation/constriction; yet, their pupils did not change in response to spatial frequency. In experiment 2, in which skates could bury into three natural substrates with different spatial frequencies, such that their eyes protruded above the substrate, the pupils showed a subtle but statistically significant response to changes in substrate spatial frequency. Given the same light intensity, the smaller the spatial frequency of the natural substrate, the more constricted the pupil. While light intensity is the primary factor determining pupil dilation, these experiments are the first to show that pupils also change in response to background spatial frequency, which suggests that the pupil may aid in camouflaging the eye.
Resolving Cytosolic Diffusive States in Bacteria by Single-Molecule Tracking
Authors: Rocha J. , Corbitt J. , Yan T. , Richardson C. , Gahlmann A. 
Published: December 2018

AbstractThe trajectory of a single protein in the cytosol of a living cell contains information about its molecular interactions in its native environment. However, it has remained challenging to accurately resolve and characterize the diffusive states that can manifest in the cytosol using analytical approaches based on simplifying assumptions. Here, we show that multiple intracellular diffusive states can be successfully resolved if sufficient single-molecule trajectory information is available to generate well-sampled distributions of experimental measurements and if experimental biases are taken into account during data analysis. To address the inherent experimental biases in camera-based and MINFLUX-based single-molecule tracking, we use an empirical data analysis framework based on Monte Carlo simulations of confined Brownian motion. This framework is general and adaptable to arbitrary cell geometries and data acquisition parameters employed in 2D or 3D single-molecule tracking. We show that, in addition to determining the diffusion coefficients and populations of prevalent diffusive states, the timescales of diffusive state switching can be determined by stepwise increasing the time window of averaging over subsequent single-molecule displacements. Time-averaged diffusion (TAD) analysis of single-molecule tracking data may thus provide quantitative insights into binding and unbinding reactions among rapidly diffusing molecules that are integral for cellular functions.
Physical activity in adolescence: cross-national comparisons of levels, distributions and disparities across 52 countries
Authors: Bann David , Scholes Shaun , Fluharty Meg , Shure Nikki 
Published: December 2018

AbstractIntroduction:Despite global concerns regarding physical inactivity, limited cross-national evidence exists to compare adolescents’ physical activity participation. We analysed 52 high- and low-middle income countries, with activity undertaken inside and outside of school in 2015. We investigated gender- and socioeconomic-disparities, and additionally examined correlations with country-level indices of physical education (PE) curriculum time allocation, wealth, and income inequality.Methods:We used the Programme for International Student Assessment (PISA), a nationally representative cross-sectional survey of 15-year-olds (N=347,935). Students reported average attendance (days/week) in PE classes, and the days/week engaged in moderate activity (MPA) and vigorous activity (VPA) outside of school. Both the mean and distributions of outcomes were evaluated, as were gender- and socioeconomic-disparities. Pearson’s correlations (r) between the physical activity outcomes and PE curriculum time allocation, wealth (indexed by GDP) and income inequality (indexed by the Gini coefficient) were calculated.Results:Activity levels inside and outside of school were higher in Eastern Europe than Western Europe, the Americas, and the Middle East/North Africa. Comparisons of average levels masked potentially important differences in distributions. For example, activity levels inside school showed a bimodal distribution in the US (mean PE class attendance 2.4 days/week; 41.3%, 6.3% and 33.1% of students attended PE classes on 0, 2 and 5 days/week respectively). In contrast, most other countries exhibited more centrally shaped distributions. Pro-male and pro-high socioeconomic disparities were modest for participation inside school, but higher for MPA and VPA outside of school. The magnitude of these also differed markedly by country. Activity in school was weakly positively correlated with PE curriculum time allocation (r=0.33); activity outside of school was strongly negatively correlated with income inequality (e.g. r=-0.69 for MPA).Conclusion:Our findings reveal extensive cross-country differences in adolescents’ physical activity; in turn, these highlight policy areas that could ultimately improve global adolescent health, such as the incorporation of minimum country-level PE classes, and the targeting of gender- and socioeconomic- disparities in activity conducted outside of school. Our findings also highlight the utility of educational databases such as PISA for use in global population health research.
The biogenesis of CLEL peptides involves several processing events in consecutive compartments of the secretory pathway
Authors: Stührwohldt Nils , Scholl Stefan , Lang Lisa , Katzenberger Julia , Schumacher Karin , Schaller Andreas 
Published: December 2018

AbstractPost-translationally modified peptides are involved in many aspects of plant growth and development. The maturation of these peptides from their larger precursors is still poorly understood. We show here that the biogenesis of CLEL6 and CLEL9 peptides in Arabidopsis thaliana requires a series of processing events in consecutive compartments of the secretory pathway. Following cleavage of the signal peptide upon entry into the endoplasmic reticulum (ER), the peptide precursors are processed in the cis-Golgi by the subtilase SBT6.1. SBT6.1-mediated cleavage within the variable domain allows for continued passage of the partially processed precursors through the secretory pathway, and is a prerequisite for subsequent post-translational modifications including tyrosine sulfation and proline hydroxylation within, and proteolytic maturation after exit from the Golgi. Activation by subtilase SBT3.8 in post-Golgi compartments depends on the N-terminal aspartate of the mature peptides. Our work highlights the complexity of post-translational precursor maturation allowing for stringent control of peptide biogenesis.
Genomic changes underlying host specialization in the bee gut symbiont Lactobacillus Firm5
Authors: Ellegaard KM , Brochet S , Bonilla-Rosso G , Emery O , Glover N , Hadadi N , Jaron KS , van der Meer JR , Robinson-Rechavi M , Sentchilo V , Tagini F ,   SAGE class 2016-17, Engel P 
Published: December 2018

AbstractBacteria that engage in longstanding associations with particular hosts are expected to evolve host-specific adaptations that limit their capacity to thrive in other environments. Consistent with this, many gut symbionts seem to have a limited host range, based on community profiling and phylogenomics. However, few studies have experimentally investigated host specialization of gut symbionts and underlying mechanisms have largely remained elusive. Here, we studied host specialization of a dominant gut symbiont of social bees, Lactobacillus Firm5. We show that Firm5 strains isolated from honey bees and bumble bees separate into deep-branching host-specific phylogenetic lineages. Despite their divergent evolution, colonization experiments show that bumble bee strains are capable of colonizing the honey bee gut. However, they were less successful than honey bee strains, and competition with honey bee strains completely abolished their colonization. In contrast honey bee strains of divergent phylogenetic lineages were able to coexist within individual bees. This suggests that both host selection and interbacterial competition play important roles for host specialization. Using comparative genomics of 27 Firm5 isolates, we found that the genomes of honey bee strains harbor more carbohydrate-related functions than bumble bee strains, possibly providing a competitive advantage in the honey bee gut. Remarkably, most of the genes encoding carbohydrate-related functions were not conserved among the honey bee strains, which suggests that honey bees can support a metabolically more diverse community of Firm5 strains than bumble bees. These findings advance our understanding of genomic changes underlying host specialization.
Interplay between somatic and dendritic inhibition promotes the emergence and stabilization of place fields
Authors: Pedrosa Victor , Clopath Claudia 
Published: December 2018

AbstractDuring exploration of novel environments, place fields are rapidly formed in hippocampal CA1 neurons. Place cell firing rate increases in early stages of exploration of novel environments but returns to baseline levels in familiar environments. However, although similar in amplitude and width, place fields in familiar environments are more stable than in novel environments. We propose a computational model of the hippocampal CA1 network, which describes the formation, the dynamics and the stabilization of place fields. We show that although somatic disinhibition is sufficient to form place cells, dendritic inhibition along with synaptic plasticity is necessary for stabilization. Our model suggests that place cell stability is due to large excitatory synaptic weights and large dendritic inhibition. We show that the interplay between somatic and dendritic inhibition balances the increased excitatory weights, so that place cells return to their baseline firing rate after exploration. Our model suggests that different types of interneurons are essential to unravel the mechanisms underlying place field plasticity. Finally, we predict that artificial induced dendritic events can shift place fields even after place field stabilization.
Evolution of Nodal and Nodal-related genes and the putative composition of the heterodimer that triggers the Nodal pathway in vertebrates
Authors: Opazo Juan C. , Kuraku Shigehiro , Zavala Kattina , Toloza-Villalobos Jessica , Hoffmann Federico G. 
Published: December 2018

AbstractNodal is a signaling molecule that belongs to the transforming growth factor-beta superfamily that plays key roles during the early stages of development of animals. Nodal forms an heterodimer with a GDF1/3 protein to activate the Nodal pathway. Vertebrates have a paralog of nodal in their genomes labeled Nodal related, but the evolutionary history of these genes is a matter of debate, mainly because of variable numbers of genes in the vertebrate genomes sequenced so far. Thus, the goal of this study was to investigate the evolutionary history of the Nodal and Nodal-related genes with an emphasis in tracking changes in the number of genes among vertebrates. Our results show the presence of two gene lineages (Nodal and Nodal-related) that can be traced back to the ancestor of jawed vertebrates. These lineages have undergone processes of differential retention and lineage-specific expansions. Our results imply that Nodal and Nodal-related duplicated at the latest in the ancestor of gnathostomes, and they still retain a significant level of functional redundancy. By comparing the evolution of the Nodal/Nodal-related with GDF1/3 gene family, it is possible to infer that there are at least four types of heterodimers that can trigger the Nodal pathway among vertebrates.
Modulation of large-scale cortical coupling by transcranial alternating current stimulation
Authors: Schwab Bettina C. , Misselhorn Jonas , Engel Andreas K. 
Published: December 2018

AbstractBackgroundLong-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value.ObjectiveFirst, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space.MethodsEEG aftereffects of bifocal high-definition tACS were analyzed systematically in sensor and source space. Participants were stimulated transcranially in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields.ResultsWhile total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120 s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipitoparietal areas.ConclusionThe relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects did not differ between stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.