bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

Explaining 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

Cervids 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

The 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

The 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

Introduction:

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

Post-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.
Frustrated binding of biopolymer crosslinkers
Authors: Mulla Yuval , Wierenga Harmen , Alkemade Celine , ten Wolde Pieter Rein , Koenderink Gijsje H.
Published: December 2018

Transiently crosslinked actin filament networks allow cells to combine elastic rigidity with the ability to deform viscoelastically. Theoretical models of semiflexible polymer networks predict that the crosslinker unbinding rate governs the timescale beyond which viscoelastic flow occurs. However a direct comparison between network and crosslinker dynamics is lacking. Here we measure the network’s stress relaxation timescale using rheology and the lifetime of bound crosslinkers using fluorescence recovery after photobleaching. lntruigingly, we observe that the crosslinker unbinding rate measured by FRAP is more than an order of magnitude slower than the rate measured by rheology. We rationalize this difference with a three-state model where crosslinkers are bound to either 0, 1 or 2 filaments, which allows us to extract crosslinker transition rates that are otherwise difficult to access. We find that the unbinding rate of singly bound crosslinkers is nearly two orders of magnitude slower than for double bound ones. We attribute the increased unbinding rate of doubly bound crosslinkers to the high stiffness of biopolymers, which frustrates crosslinker binding.
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

Bacteria 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.
Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis
Authors: Viehweger Adrian , Krautwurst Sebastian , Lamkiewicz Kevin , Madhugiri Ramakanth , Ziebuhr John , Hölzer Martin , Marz Manja
Published: December 2018

Sequence analyses of RNA virus genomes remain challenging due to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called 'quasispecies'. Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (i) RNA virus genomes and (ii) subgenome-length (sg) RNAs comprised of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. Using DRS, we were able to map the longest (~26 kb) contiguous read to the viral reference genome. By combining Illumina and nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV) 229E genome (27.3 kb). Furthermore, using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by demonstrating the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that direct RNA sequencing may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.
Interplay between somatic and dendritic inhibition promotes the emergence and stabilization of place fields
Authors: Pedrosa Victor , Clopath Claudia
Published: December 2018

During 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

Nodal 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

Background

Long-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.

Objective

First, 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.

Methods

EEG 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.

Results

While 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.

Conclusion

The 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.
Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination
Authors: Sun Hequan , Rowan Beth A. , Flood Pádraic J. , Brandt Ronny , Fuss Janina , Hancock Angela M. , Michelmore Richard W. , Huettel Bruno , Schneeberger Korbinian
Published: December 2018

Meiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Existing methods for CO identification are challenged by large populations and the demand for genome-wide and fine-scale resolution. Taking advantage of linked-read sequencing, we developed a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first tested this method using a pool of Arabidopsis F2 recombinants, and obtained results that recapitulated those identified from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from a single F1 plant, we established a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach now enables the simultaneous generation and analysis of multiple CO landscapes and thereby allows for efficient comparison of genotypic and environmental effects on recombination, accelerating the pace at which the mechanisms for the regulation of recombination can be elucidated.
Who’s who in the western Hermann’s tortoise conservation: a STR toolkit and reference database for wildlife forensic genetic analyses
Authors: Roberto Biello , Mauro Zampiglia , Claudia Corti , Gianluca Deli , Marta Biaggini , Michel Delaugerre , Luciano Di Tizio , Luigi Leonetti Francesco , Oliviero Olivieri , Francesco Pellegrino , Antonio Romano , Emilio Sperone , Massimo Trabalza-Marinucci , Giorgio Bertorelle , Daniele Canestrelli
Published: December 2018

Illegal trade is threatening tortoise populations worldwide since decades. Nowadays, however, DNA typing and forensic genetic approaches allow to investigate geographic origin of confiscated animals and to relocate them into the wild, provided that suitable molecular tools and reference data are available. Here we assess the suitability of a small panel of microsatellite markers to investigate patterns of illegal translocations and to assist forensic genetic applications in the endangered Mediterranean land tortoiseTestudo hermanni hermanni. We used the microsatellite panel to (i) increase the understanding of the population genetic structure in wild populations with new data from previously unsampled geographic areas (overall 461 wild individuals from 28 sampling sites); (ii) detect the presence of non-native individuals in wild populations; and (iii) identify the most likely geographic area of origin of 458 confiscated individuals hosted in Italian seizure and recovery centers. Our analysis initially identified six major genetic clusters corresponding to different geographic macro-areas along the Mediterranean range. Long-distance migrants among wild populations, due to translocations, were found and removed from the reference database. Assignment tests allowed us to allocate approximately 70% of confiscated individuals of unknown origin to one of the six Mediterranean macro-areas. Most of the assigned tortoises belonged to the genetic cluster corresponding to the area where the respective captivity center was located. However, we also found evidence of long-distance origin of confiscated individuals, especially in centers along the Adriatic coast and facing the Balkan regions, a well-known source of illegally traded individuals. Our results clearly show the role for reintroduction projects of the microsatellite panel, which was useful to re-assign most of the confiscated individuals to the respective macro-area of origin. At the same time, the microsatellite panel can assist future forensic genetic applications to detect illegal trade and possess ofTestudo hermanniindividuals.
Genetic, structural, and functional analysis of mutations causing methylmalonyl-CoA epimerase deficiency
Authors: Heuberger Kathrin , Bailey Henry J. , Burda Patricie , Chaikuad Apirat , Krysztofinska Ewelina , Suormala Terttu , Bürer Céline , Lutz Seraina , Fowler Brain , Froese D. Sean , Yue Wyatt W. , Baumgartner Matthias R.
Published: December 2018

Human methylmalonyl-CoA epimerase (MCEE) catalyzes the interconversion of D-methylmalonyl-CoA and L-methylmalonyl-CoA in propionate catabolism. Autosomal recessive mutations inMCEEreportedly cause methylmalonic aciduria (MMAuria) in eleven patients. We investigated a cohort of 150 individuals suffering from MMAuria of unknown origin, identifying ten new patients with mutations inMCEE. Nine patients were homozygous for the known nonsense mutation p.Arg47* (c.139C>T), and one for the novel missense mutation p.Ile53Arg (c.158T>G). To understand better the molecular basis of MCEE deficiency, we mapped p.Ile53Arg, and two previously described patient mutations p.Lys60Gln and p.Arg143Cys, onto our 1.8 Å structure of wild-type (wt) human MCEE. This revealed potential dimeric assembly disruption by p.Ile53Arg, but no clear defects from p.Lys60Gln or p.Arg143Cys. Functional analysis of MCEE-Ile53Arg expressed in a bacterial recombinant system as well as patient-derived fibroblasts revealed nearly undetectable soluble protein levels, defective globular protein behavior, and using a newly developed assay, lack of enzymatic activity - consistent with misfolded protein. By contrast, soluble protein levels, unfolding characteristics and activity of MCEE-Lys60Gln were comparable to wt, leaving unclear how this mutation may cause disease. MCEE-Arg143Cys was detectable at comparable levels to wt MCEE, but had slightly altered unfolding kinetics and greatly reduced activity. We solved the structure of MCEE-Arg143Cys to 1.9 Å and found significant disruption of two important loop structures, potentially impacting surface features as well as the active-site pocket. These studies reveal ten new patients with MCEE deficiency and rationalize misfolding and loss of activity as molecular defects in MCEE-type MMAuria.
Soil microbial communities in diverse agroecosystems exposed to glyphosate
Authors: Kepler Ryan M. , Epp Schmidt Dietrich J. , Yarwood Stephanie A. , Reddy Krishna N. , Duke Stephen O. , Bradley Carl A. , Williams Martin M. , Buyer Jeffery , Cavigelli Michel A. , Maul Jude E.
Published: December 2018

In spite of glyphosate’s wide use in agriculture, questions remain about effects of the herbicide on soil microbial communities. Conflicting scientific literature reports divergent results; from no observable effect of glyphosate to the enrichment of common agricultural pathogens such as Fusarium. We conducted a comprehensive field-based study to compare treatments that did and did not receive foliar application of glyphosate spray. The study included two field sites, Maryland and Mississippi; two crops, soybean and corn; four site years, 2013 and 2014; and a variety of organic and conventional farming systems. Using amplicon sequencing, the prokaryotic (16S rRNA) and fungal (ITS) communities were described along with chemical and physical properties of the soil. Sections of corn and soy roots were plated to screen for the presence of plant pathogens. Geography, farming system, and seasonal progression were significant factors determining composition of fungal and bacterial communities. Plots treated with or without glyphosate did not differ in overall microbial community composition after controlling for these factors. No differential effect of glyphosate treatment was found in the relative abundance of organisms such as Fusarium spp. or putative growth-promoting bacteria Pseudomonas spp.
Pervasive Adaptation of Hepatitis C Virus to Interferon Lambda Polymorphism Across Multiple Genotypes
Authors: Chaturvedi Nimisha , Svarovskaia Evguenia S. , Mo Hongmei , Osinusi Anu O. , Brainard Diana M. , Subramanian G Mani , McHutchison John G. , Zeuzem Stefan , Fellay Jacques
Published: December 2018

Genetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and with response to interferon-based antiviral treatment. Here, we evaluate the associations between IFN- λ polymorphism and HCV variation through a genome-to-genome analysis in 8,729 patients from diverse ancestral backgrounds infected with various HCV genotypes. We searched for associations between rs12979860 genotype, a tag for IFN-λ haplotypes, and amino acid variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations between host and pathogen variants in the full cohort as well as in subgroups defined by viral genotype and human ancestry. We also assess the combined impact of human and HCV variation on pre-treatment viral load. By demonstrating that IFN-λ genetic variation leaves a large footprint in the viral genome, this study provides strong evidence of pervasive viral adaptation to host innate immune pressure during chronic HCV infection.
Coupling and Decoupling between Brain and Body Oscillations
Authors: Rassi Elie , Dorffner Georg , Gruber Walter , Klimesch Wolfgang
Published: December 2018

Cross frequency coupling is used intensively to study the cross talk between brain oscillations. In this paper we focus on a special type of frequency coupling between brain and body oscillations, which is reflected by the numerical ratio (r) between two frequencies (m and n; n > m). This approach is motivated by theoretical considerations indicating that an integer relationship (r = n/m = integer number) reflects coupling, whereas an irrational relationship (r = n/m = irrational number) reflects decoupling. We analyzed alpha frequency, heart rate, breathing frequency and spindle frequency from data collected by the SIESTA research group. Our results show a 1:4 frequency relationship between heart rate and breathing frequency both during wakefulness and sleep. During wakefulness we expected but did not find an integer relationship between alpha frequency and heart rate or alpha frequency and breathing frequency. During sleep, we observed an irrational relationship between spindle frequency and heart rate as well as spindle frequency and breathing frequency–suggesting decoupling.
Single cell derived organoids capture the self-renewing subpopulations of metastatic ovarian cancer
Authors: Velletri Tania , Villa Emanuele Carlo , Lupia Michela , Riso Pietro Lo , Luongo Raffaele , Tobon Alejandro Lopez , Simone Marco De , Bonnal Raoul J.P. , Minucci Saverio , Piccolo Stefano , Colombo Nicoletta , Pagani Massimiliano , Cavallaro Ugo , Testa Giuseppe
Published: December 2018

High Grade Serous Ovarian cancer (HGSOC) is a major unmet need in oncology, due to its precocious dissemination and the lack of meaningful human models for the investigation of disease pathogenesis in a patient-specific manner. To overcome this roadblock, we present a new method to isolate and grow single cells directly from patients’ ascites, establishing the conditions for propagating them as single-cell derived ovarian cancer organoids (scOCOs). By single cell RNA sequencing (scRNAseq) we define the cellular composition of metastatic ascites and trace its propagation in 2D and 3D culture paradigms, finding that scOCOs retain and amplify key subpopulations from the original patients’ samples and recapitulate features of the original metastasis that do not emerge from classical 2D culture, including retention of individual patients’ specificities. By enabling the enrichment of uniquely informative cell subpopulations from HGSOC metastasis and the clonal interrogation of their diversity at the functional and molecular level, this method transforms the prospects of precision oncology for ovarian cancer.
Hierarchical Stem Cell Topography Splits Growth and Homeostatic Functions in the Fish Gill
Authors: Stolper Julian , Ambrosio Elizabeth , Danciu Diana-P , Elliot David A. , Naruse Kiyoshi , Czochra Anna Marciniak , Centanin Lazaro
Published: December 2018

While lower vertebrates contain adult stem cells (aSCs) that maintain homeostasis and drive un-exhaustive organismal growth, mammalian aSCs display mainly the homeostatic function. Understanding aSC-driven growth is of paramount importance to promote organ regeneration and prevent tumor formation in mammals. Here we present a clonal approach to address common or dedicated populations of aSCs for homeostasis and growth. Our functional assays on medaka gills demonstrate the existence of separate homeostatic and growth aSCs, which are clonal but differ in their topology. While homeostatic aSCs are fixed, embedded in the tissue, growth aSCs locate at the expanding peripheral zone. Modifications in tissue architecture can convert the homeostatic zone into a growth zone, indicating a leading role for the physical niche defining stem cell output. We hypothesize that physical niches are main players to restrict aSCs to a homeostatic function in animals with a fixed adult size.
Science Family skills: An Alexa Assistant Tailored for Laboratory Routine
Authors: Lubiana-Alves Tiago , Gonçalves André A.N.A. , Nakaya Helder I
Published: December 2018

Voice User Interfaces such as Amazon Alexa and Google Home are already widely available and used for personal purposes. These services could be used to improve experimental biology laboratory routine, facilitate troubleshooting and increase efficiency. Till date, no applications that are tailored to enhance laboratory routine have been made available. Here, we present a set of free-to-use, open source tools adapted to Alexa for application in the laboratory environment, with prospects of enhancing productivity and reducing work-related stress. All skills, 3D printer model and source codes are freely available in the Alexa app store and in GitHub.
MLL-AF9 Initiates Transformation From Fast-Proliferating Myeloid Progenitors
Authors: Chen Xinyue , Hartman Amaleah , Hu Xiao , Eastman Anna E. , Wang Xujun , Zhong Mei , Guo Shangqin
Published: December 2018

Cancer is a hyper-proliferative clonal disease. Whether the proliferative state originates from the cell-of-origin or emerges later remains elusive. By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte-macrophage progenitors (GMPs) determines their probability of transformation. An intrinsic fast cell cycle kinetics at the time of oncogene expression provide permissiveness for transformation, with the fastest cycling 3% of GMPs (∼0.006% of bone marrow nucleated cells) acquiring malignancy with nearly 100% efficiency. Molecularly, we propose that MLL-AF9 preserves the gene expression of the cellular states in which it is expressed. As such, when expressed in the naturally-existing, rapidly-cycling myeloid progenitors, this cell state is perpetuated, yielding malignancy. Our work elucidates one of the earliest steps toward malignancy and suggests that modifying the cycling state of the cell-of-origin could be an effective approach to prevent malignancy.
Usefulness Criterion and post-selection Parental Contributions in Multi-parental Crosses: Application to Polygenic Trait Introgression
Authors: Allier Antoine , Moreau Laurence , Charcosset Alain , Teyssèdre Simon , Lehermeier Christina
Published: December 2018

Predicting the usefulness of crosses in terms of expected genetic gain and genetic diversity is of interest to secure performance in the progeny and to maintain long-term genetic gain in plant breeding. A wide range of crossing schemes are possible including large biparental crosses, backcrosses, four-way crosses, and synthetic populations.In silicoprogeny simulations together with genome-based prediction of quantitative traits can be used to guide mating decisions. However, the large number of multi-parental combinations can hinder the use of simulations in practice. Analytical solutions have been proposed recently to predict the distribution of a quantitative trait in the progeny of biparental crosses using information of recombination frequency and linkage disequilibrium between loci. Here, we extend this approach to obtain the progeny distribution of more complex crosses including two to four parents. Considering agronomic traits and parental genome contribution as jointly multivariate normally distributed traits, the usefulness criterion parental contribution (UCPC) enables to (i) evaluate the expected genetic gain for agronomic traits, and at the same time (ii) evaluate parental genome contributions to the selected fraction of progeny. We validate and illustrate UCPC in the context of multiple allele introgression from a donor into one or several elite recipients in maize (Zea maysL.). Recommendations regarding the interest of two-way, three-way, and backcrosses were derived depending on the donor performance. We believe that the computationally efficient UCPC approach can be useful for mate selection and allocation in many plant and animal breeding contexts.
Cardiac afferent activity modulates early neural signature of error detection during skilled performance
Authors: Bury Gabriela , Huesca Marta García , Bhattacharya Joydeep , Ruiz María Herrojo
Published: December 2018

Behavioral adaptations during performance rely on predicting and evaluating the consequences of our actions through action monitoring. Previous studies revealed that proprioceptive and exteroceptive signals contribute to error-monitoring processes, which are implemented in the posterior medial frontal cortex. Interestingly, errors also trigger changes in autonomic nervous system activity such as pupil dilation or heartbeat deceleration. Yet, the contribution of implicit interoceptive signals of bodily states to error-monitoring during ongoing performance has been overlooked.

This study investigated whether cardiovascular interoceptive signals influence the neural correlates of error processing during performance, with an emphasis on the early stages of error processing. We recorded musicians’ electroencephalography and electrocardiogram signals during the performance of highly-trained music pieces. Previous event-related potential (ERP) studies revealed that pitch errors during skilled musical performance are preceded by an error detection signal, the pre-error-negativity (preERN), and followed by a later error positivity (PE). In this study, by combining ERP, source localization and multivariate pattern classification analysis, we found that the error-minus-correct ERP waveform had an enhanced amplitude within 40-100 ms following errors in the systolic period of the cardiac cycle. This component could be decoded from singletrials, was dissociated from the preERN and PE, and stemmed from the inferior parietal cortex, which is a region implicated in cardiac autonomic regulation. In addition, the phase of the cardiac cycle influenced behavioral alterations resulting from errors, with a smaller post-error slowing and less perturbed velocity in keystrokes following pitch errors in the systole relative to the diastole phase of the cardiac cycle. Lastly, changes in the heart rate anticipated the upcoming occurrence of errors. This study provides the first evidence of preconscious visceral information modulating neural and behavioral responses related to early error monitoring during skilled performance.
An individual-based mechanical model of cell movement in heterogeneous tissues and its coarse-grained approximation
Authors: Murphy R. J. , Buenzli P. R. , Baker R. E. , Simpson M. J.
Published: December 2018

Mechanical heterogeneity in biological tissues, in particular stiffness, can be used to distinguish between healthy and diseased states. However, it is often difficult to explore relationships between cellular-level properties and tissue-level outcomes when biological experiments are performed at a single scale only. To overcome this difficulty we develop a multi-scale mathematical model which provides a clear framework to explore these connections across biological scales. Starting with an individual-based mechanical model of cell movement, we subsequently derive a novel coarse-grained system of partial differential equations governing the evolution of the cell density due to heterogeneous cellular properties. We demonstrate that solutions of the individual-based model converge to numerical solutions of the coarse-grained model, for both slowly-varying-in-space and rapidly-varying-in-space cellular properties. Applications of the model are discussed, including determining relative cellular-level properties and an interpretation of data from a breast cancer detection experiment.
Arabidopsis TRM5 encodes a nuclear-localised bifunctional tRNA guanine and inosine-N1-methyltransferase that is important for growth
Authors: Guo Q. , Ng PQ. , Shi S. , Fan D. , Li J. , Wang H. , Do T. , David R. , Mittal P. , Bock R. , Zhao M. , Zhou W. , Searle I. R.
Published: December 2018

Modified nucleosides in tRNAs are critical for protein translation. N1-methylguanosine-37 and N1-methylinosine-37 in tRNAs, both located at the 3’-adjacent to the anticodon, are formed by Trm5 and here we describe Arabidopsis thaliana AtTrm5 (At3g56120) as a Trm5 ortholog. We show that AtTrm5 complements the yeast trm5 mutant, and in vitro methylates tRNA guanosine-37 to produce N1-methylguanosine (m1G). We also show in vitro that AtTRM5 methylates tRNA inosine-37 to produce N1-methylinosine (m1I) and in Attrm5 mutant plants, we show a reduction of both N1-methylguanosine and N1-methylinosine. We also show that AtTRM5 is localized to the nucleus in plant cells. Attrm5 mutant plants have overall slower growth as observed by slower leaf initiation rate, delayed flowering and reduced primary root length. In Attrm5 mutants, mRNAs of flowering time genes are less abundant and correlated with delayed flowering. Finally, proteomics data show that photosynthetic protein abundance is affected in mutant plants. Our findings highlight the bifunctionality of AtTRM5 and the importance of the post-transcriptional tRNA modifications m1G and m1I at tRNA position 37 in general plant growth and development.
Bertelsmann China: Supply Chains for Books (B)
Authors: Wagner Stephan M. , Heldt Viviane , Lentschig Katrin , Meyer Jennifer
Published: December 2018

The case of Bertelsmann China: Supply Chain for Books (B) is situated in China in the beginning of 2006. Bertelsmann Direct Group, the Chinese subsidiary of the worldwide Bertelsmann AG, is one of the leading book retailers in the country. Supply chain management is essential for success in retailing, which is why Bertelsmann puts a lot of effort into the optimization of its supply chain design. As costs are paramount to importance in the low-margin book retailing sector, linear programming methods are applied to optimize the network
Expanding Warehouse Operations at Goodwill Industries
Authors: Ross Anthony , Kosfeld Mark
Published: December 2018

Goodwill Industries warehousing operations has increased as the Used Merchandise Store Sales in the US has also increased to a total spending of $17 billion in 2013. Goodwill Industries faces warehousing issues as their inventory fluctuates seasonally. As people do their spring cleaning in the beginning of the year and rush to get their tax-deductible donations in by the end of the year, the warehouses are overflowed but in the off-seasons they are scarce. The following case poses the issue of an efficient warehouse operation that also supports the company sales plan.
An experiential approach to learning about change management
Authors: Vandangeon-Derumez Isabelle , Djedidi Amina , Szendy Eila
Published: December 2018

Purpose

The purpose of this paper is to focus on the role of experience in learning about, and preparing for, change management.

Design/methodology/approach

A course with a different approach to teaching about change management has been proposed to learners. It uses drawing, simulation and exploration of case studies. Learners wrote reports on change management before and after the course and these reports were then thematically analyzed.

Findings

Results show the specific ways in which the course places learners in a position to: experience change, use their collective experiences, acquire and develop practical knowledge, and prepare themselves for change. Capitalizing on such experiences of change could arguably become an integral part of an organization’s “readiness to change” strategy.

Research limitations/implications

It would be useful to further investigate what happens after this experience by interviewing learners, later on, in order to analyze how they subsequently use, in a real professional environment, such knowledge and skills acquired during the learning process.

Practical implications

Using this approach, future managers are arguably better prepared to implement change. Capitalizing on such experiences of change could become part of an organization’s “readiness for change” strategy.

Social implications

The benefits of experiencing change management in a learning environment will only be reaped when firms allocate time and space to such experiential learning. This entails going beyond managing this change to a deeper perspective by identifying key elements to maintain and/or enhance one’s experience of managing change.

Originality/value

The value of the present paper lies in individual and collective experience as a key element to prepare managers to change management.