bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Diverse Range of Factors Affect the Nature of Neural Representations Underlying Short-Term Memory
Authors: Orhan A. Emin , Ma Wei Ji 
Published: January 2018

AbstractSequential and persistent activity models are two prominent models of short-term memory in neural circuits. In persistent activity models, memories are represented in persistent or nearly persistent activity patterns across a population of neurons, whereas in sequential models, memories are represented dynamically by a sequential pattern of activity across the population. Experimental evidence for both types of model in the brain has been reported previously. However, it has been unclear under what conditions these two qualitatively different types of solutions emerge in neural circuits. Here, we address this question by training recurrent neural networks on several short-term memory tasks under a wide range of circuit and task manipulations. We show that sequential and nearly persistent solutions are both part of a spectrum that emerges naturally in trained networks under different conditions. Fixed delay durations, tasks with higher temporal complexity, strong network coupling, motion-related dynamic inputs and prior training in a different task favor more sequential solutions, whereas variable delay durations, tasks with low temporal complexity, weak network coupling and symmetric Hebbian short-term synaptic plasticity favor more persistent solutions. Our results help clarify some seemingly contradictory experimental results on the existence of sequential vs. persistent activity based memory mechanisms in the brain.
Validating a 14-drug microtitre plate containing bedaquiline and delamanid for large-scale research susceptibility testing ofMycobacterium tuberculosis
Authors: Rancoita Paola MV , Cugnata Federica , Cruz Ana Luíza Gibertoni , Borroni Emanuele , Hoosdally Sarah J , Walker Timothy M , Grazian Clara , Davies Timothy J , Peto Timothy EA , Crook Derrick W , Fowler Philip W , Cirillo Daniela M ,   the CRyPTIC Consortium
Published: January 2018

ABSTRACTUKMYC5 is a 96-well microtitre plate designed by theComprehensive Resistance Prediction for Tuberculosis: an International Consortium(CRyPTIC) to enable the measurement of minimum inhibitory concentrations (MICs) of 14 different anti-TB compounds for >30,000 clinical tuberculosis isolates. Unlike the MYCOTB plate, on which UKMYC5 is based, the plate included two new (bedaquiline and delamanid) and two repurposed (clofazimine and linezolid) compounds. UKMYC5 plates were tested by seven laboratories on four continents using a panel of 19 external quality assessment (EQA) strains, including H37Rv. To assess the optimal combination of reading method and incubation time, MICs were measured from each plate by two readers using three methods (mirrored-box, microscope and Vizion™ Digital viewing system) after 7, 10, 14 and 21 days incubation. In addition, all EQA strains were whole-genome sequenced and phenotypically characterized by 7H10/7H11 agar proportion method (APM) and MGIT960. We conclude that the UKMYC5 plate is optimally read using the Vizion™ system after 14 days incubation, achieving an inter-reader agreement of 97.9% and intra- and inter-laboratory reproducibilities of 95.6% and 93.1%, respectively. The mirrored-box had similar reproducibilities. Strains classified as resistant by APM, MGIT960 or the presence of mutations known to confer resistance consistently record elevated MICs compared with those strains classified as susceptible. Finally, the UKMYC5 plate records intermediate MICs for one strain which the APM measured MICs close the applied critical concentration, providing early evidence that the UKMYC5 plate can quantitatively measure the magnitude of resistance to anti-TB compounds due to specific genetic variation.
Integration of Brassinosteroid and Phytosulfokine Signalling Controls Vascular Cell Fate in the Arabidopsis Root
Authors: Holzwart Eleonore , Huerta Apolonio Ignacio , Glöckner Nina , Gómez Borja Garnelo , Ladwig Friederike , Augustin Sebastian , Askani Jana Christin , Schürholz Ann-Kathrin , Harter Klaus , Wolf Sebastian 
Published: January 2018

AbstractMulticellularity arose independently in plants and animals, but invariably requires robust determination and maintenance of cell fate. This is exemplified by the highly specialized water-and nutrient-conducting cells of the plant vasculature, which are specified long before their commitment to terminal differentiation. Here, we show that the hormone receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is required for root vascular cell fate maintenance, as BRI1 mutants show ectopic xylem in procambial position. However, this phenotype is unrelated to classical brassinosteroid signalling outputs. Instead, BRI1 is required for the expression and function of its interaction partner RECEPTOR-LIKE PROTEIN 44 (RLP44), which, in turn, associates with the receptor for the peptide hormone phytosulfokine (PSK). We show that PSK signalling is required for the maintenance of procambial cell identity and is quantitatively controlled by RLP44, which promotes complex formation between the receptor for PSK and its co-receptor. Mimicking the loss of RLP44, PSK-related mutants show ectopic xylem in the position of procambium, whereas rlp44 can be rescued by exogenous PSK. Based on these findings, we propose that RLP44 controls cell fate by connecting BRI1 and PSK signalling, providing a mechanistic framework for the integration of signalling mediated by the plethora of plant receptor-like kinases at the plasma membrane.
Phylogenomics and barcoding ofPanax: toward the identification of ginseng species
Authors: Manzanilla V. , Kool A. , Nguyen Nhat L. , Nong Van H. , Le Thi Thu H. , de Boer H.J. 
Published: January 2018

AbstractBackgroundThe economic value of ginseng in the global medicinal plant trade is estimated to be in excess of US$2.1 billion. At the same time, the evolutionary placement of ginseng (Panax ginseng) and the complex evolutionary history of the genus is poorly understood despite several molecular phylogenetic studies. In this study, we use a full plastome phylogenomic framework to resolve relationships inPanaxand to identify molecular markers for species discrimination.ResultsWe used high-throughput sequencing of MBD2-Fc fractionatedPanaxDNA to supplement publicly available plastid genomes to create a phylogeny based on fully assembled and annotated plastid genomes from 60 accessions of 8 species. The plastome phylogeny based on a 163 kbp matrix resolves the sister relationship ofPanax ginsengwithP. quinquefolius. The closely related speciesP. vietnamensisis supported as sister ofP. japonicus. The plastome matrix also shows that the markerstrnC-rps16, trnS-trnG, andtrnE-trnMcould be used for unambiguous molecular identification of all the represented species in the genus.ConclusionsMBD2 depletion reduces the cost of plastome sequencing, which makes it a cost-effective alternative to Sanger sequencing based DNA barcoding for molecular identification. The plastome phylogeny provides a robust framework that can be used to study the evolution of morphological characters and biosynthesis pathways of ginsengosides for phylogenetic bioprospecting. Molecular identification of ginseng species is essential for authenticating ginseng in international trade and it provides an incentive for manufacturers to create authentic products with verified ingredients.
Oscillating bacterial expression states generate herd immunity to viral infection
Authors: Turkington Christopher J. R. , Morozov Andrey , Clokie Martha R. J. , Bayliss Christopher D. 
Published: January 2018

AbstractHypermutable loci are widespread in bacteria as mechanisms for rapid generation of phenotypic diversity, enabling individual populations to survive fluctuating, often antagonistic, selection pressures. As observed for adaptive immunity, hypermutation may facilitate survival of multiple, spatially-separated bacterial populations. We developed an ‘oscillating prey assay’ to examine bacteriophage (phage) spread through populations ofHaemophilus influenzaewhose phage receptor gene,lic2A, is switched ‘ON’ and ‘OFF’ by mutations in a hypermutable tetranucleotide repeat tract. Phage extinction was frequently observed when the proportion of phage-resistant sub-populations exceeded 34%.In silicomodelling indicated that phage extinction was interdependent on phage loss during transfer between populations and the frequency of resistant populations. In a fixed-area oscillating prey assay, heterogeneity in phage resistance was observed to generate vast differences in phage densities across multiple bacterial populations resulting in protective quarantining of some populations from phage attack. We conclude that phase-variable hypermutable loci produce bacterial ‘herd immunity’ with resistant intermediary-populations acting as a barricade to reduce the viral load faced by phage-sensitive sub-populations. This paradigm of meta-population protection is applicable to evolution of hypermutable loci in multiple bacteria-phage and host-pathogen interactions.ImportanceHerd immunity is a survival strategy wherein populations are protected against invading pathogens by resistant individuals within the population acting as a barrier to spread of the infectious agent. Although, this concept is normally only applied to higher eukaryotes, prokaryotic organisms also face invasion by infectious agents, such as bacterial viruses, bacteriophage (phage). Here we use novel experimental approaches and mathematical modelling, to show that bacteria exhibit a form of herd immunity through stochastically generated resistant variants acting as barricades to phage predation of sensitive cells. With hypermutable loci found in many prokaryotic systems, this phenomenon may be widely applicable to phage-bacteria interactions and could even impact phage-driven evolution in bacteria.
Speciation genes are more likely to have discordant gene trees
Authors: Wang Richard J. , Hahn Matthew W. 
Published: January 2018

AbstractSpeciation genes are responsible for reproductive isolation between species. By directly participating in the process of speciation, the genealogies of isolating loci have been thought to more faithfully represent species trees. The unique properties of speciation genes may provide valuable evolutionary insights and help determine the true history of species divergence. Here, we formally analyze whether genealogies from loci participating in Dobzhansky-Muller (DM) incompatibilities are more likely to be concordant with the species tree under incomplete lineage sorting (ILS). Individual loci differ stochastically from the true history of divergence with a predictable frequency due to ILS, and these expectations—combined with the DM model of intrinsic reproductive isolation from epistatic interactions—can be used to examine the probability of concordance at isolating loci. Contrary to existing verbal models, we find that reproductively isolating loci that follow the DM model are often more likely to have discordant gene trees. These results are dependent on the pattern of isolation observed between three species, the time between speciation events, and the time since the last speciation event. Results supporting a higher probability of discordance are found for both derived-derived and derived-ancestral DM pairs, and regardless of whether incompatibilities are allowed or prohibited from segregating in the same population. Our overall results suggest that DM loci are unlikely to be especially useful for reconstructing species relationships, even in the presence of gene flow between incipient species, and may in fact be positively misleading.
Genotype Imputation Performance of Three Reference Panels Using African Ancestry Individuals
Authors: Vergara Candelaria , Parker Margaret M. , Franco Liliana , Cho Michael H. , Valencia-Duarte Ana V. , Beaty Terri H. , Duggal Priya 
Published: January 2018

ABSTRACTGenotype imputation is used to estimate unobserved genotypes from genome-wide maker data, to increase genome coverage and power for genome-wide association studies. Imputation has been most successful for European ancestry populations in which very large reference panels are available. Smaller subsets of African descent populations are available in 1000 Genomes (1000G), the Consortium on Asthma among African-Ancestry Populations in the Americas (CAAPA) and the Haplotype Reference Consortium (HRC). We aimed to compare the performance of these reference panels when imputing variation in 3,747 African Americans (AA) from 2 cohorts (HCV and COPDGene) genotyped using the Illumina Omni family of microarrays. The haplotypes of 2,504 individuals (from 1000G), 883 (from CAAPA) and 32,611 (from HRC) were used as reference. We compared the performance of these panels based on number of variants, imputation quality, imputation accuracy and coverage. In both cohorts, 1000G imputed 1.5–1.6x more variants compared to CAAPA and 1.2x more variants than HRC. Similar findings were observed for variants with higher imputation quality (R2>0.5) and for rare, low frequency, and common variants. When merging the results of the three panels the total number of imputed variants was 62M-63M with 20M overlapping variants imputed by all three panels, and a range of 5 to 15M unique variants imputed exclusively with one of the three panels. For overlapping variants, imputation quality was highest for HRC, followed by 1000G, then CAAPA, and improved as the minor allele frequency increased. The 1000G, HRC and CAAPA participants of African ancestry provided high performance and accuracy for imputation of African American admixed individuals, increasing the total number of variants with high quality available for subsequent analyses. These three panels are complementary and would benefit from the development of an integrated African reference panel, including data from multiple sources and populations.
An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer ofHLA-F
Authors: Mika Katelyn M. , Li Xilong , DeMayo Francesco J. , Lynch Vincent J. 
Published: January 2018

AbstractVariation in female reproductive traits such as fertility, fecundity, and fecundability are heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits has been challenging. Here we explore the functional significance and evolutionary history of a G/A polymorphism of SNP rs2523393, which we have previously shown is an eQTL for theHLA-Fgene and significantly associated with fecundability (time to pregnancy). We replicated the association between rs2523393 genotype andHLA-Fexpression using GTEx data and demonstrate thatHLA-Fis up-regulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. Next, we show that the rs2523393 A allele creates a new GATA2 binding site in a progesterone responsive distal enhancer that loops to theHLA-Fpromoter. Remarkably, we found that the A allele is derived in the human lineage, that G/A polymorphism arose before the divergence of modern and archaic humans, and is segregating at intermediate to high frequencies across human populations. Remarkably, the derived A is also has been identified in a GWAS as a risk allele for multiple sclerosis. These data suggests that the polymorphism is maintained by antagonistic pleiotropy and a reproduction-health tradeoff in human evolution.
The human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments
Authors: Helgeson Luke A. , Zelter Alex , Riffle Michael , MacCoss Michael J. , Asbury Charles L. , Davis Trisha N. 
Published: January 2018

ABSTRACTAccurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore-microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex-microtubule interaction is sufficiently strong to make a significant contribution to kinetochore-microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phospho-regulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Crosslinking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C-terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together our results indicate that the Ska complex can directly strengthen the kinetochore microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule.SIGNIFICANCE STATEMENTMicrotubules are dynamic, tube-like structures that drive the segregation of duplicated chromosomes during cell division. The Ska complex is part of a molecular machine that forms force-bearing connections between chromosomes and microtubule ends. Depletion of the Ska complex destabilizes these connections and disrupts cell division. The Ska complex binds microtubules but it is unknown if it directly holds force at microtubules or indirectly stabilizes the connections. Here, we show that the Ska complex makes a direct force-bearing linkage with microtubule ends and assembles with another microtubule binding component, the Ndc80 complex, to strengthen its ability to withstand force. Our results suggest that the Ska and Ndc80 complexes work together to maintain the connections between chromosomes and microtubule ends.
Variability in β-catenin pulse dynamics in a stochastic cell fate decision inC. elegans
Authors: Kroll Jason R. , Tsiaxiras Jasonas , van Zon Jeroen S. 
Published: January 2018

AbstractDuring development, cell fate decisions are often highly stochastic, but with the frequency of the different possible fates tightly controlled. To understand how signaling networks control the cell fate frequency of such random decisions, we studied the stochastic decision of theCaenorhabditis elegansP3.p cell to either fuse to the hypodermis or assume vulva precursor cell fate. Using time-lapse microscopy to measure the single-cell dynamics of two key inhibitors of cell fusion, the Hox gene LIN-39 and Wnt signaling through the β-catenin BAR-1, we uncovered significant variability in the dynamics of LIN-39 and BAR-1 levels. Most strikingly, we observed that BAR-1 accumulated in a single, 1-4 hour pulse at the time of the P3.p cell fate decision, with strong variability both in pulse slope and time of pulse onset. We found that the time of BAR-1 pulse onset was delayed relative to the time of cell fusion in mutants with low cell fusion frequency, linking BAR-1 pulse timing to cell fate outcome. Overall, a model emerged where animal-to-animal variability in LIN-39 levels and BAR-1 pulse dynamics biases cell fate by modulating their absolute level at the time cell fusion is induced. Our results highlight that timing of cell signaling dynamics, rather than its average level or amplitude, could play an instructive role in determining cell fate.Article summaryWe studied the stochastic decision of theCaenorhabditis elegansP3.p cell to either fuse to the hypodermis or assume vulva precursor cell fate. We uncovered significant variability in the dynamics of LIN-39/Hox and BAR-1/β-catenin levels, two key inhibitors of cell fusion. Surprisingly, we observed that BAR-1 accumulated in a 1-4 hour pulse at the time of the P3.p cell fate decision, with variable pulse slope and time of pulse onset. Our work suggests a model where animal-to-animal variability in LIN-39 levels and BAR-1 pulse dynamics biases cell fate by modulating their absolute level at the time cell fusion is induced.
Paired learning – improving collaboration between clinicians and managers
Authors: Houston James F.B. , Morgan Jessica E. 
Published: January 2018

Purpose
Close collaboration between NHS clinicians and managers is essential in providing effective healthcare, but relationships between the two groups are often poor. Paired learning is a peer-peer buddying tool that can break down barriers, increase knowledge and change attitudes. Paired learning has been used with doctors and managers but not for multi-professional clinicians. The purpose of this paper is to assess whether a paired learning programme (PLP) can improve knowledge and attitudes between multi-professional NHS clinicians and managers.

Design/methodology/approach
A PLP pairing clinicians and managers over a four-month period to participate in four buddy meetings and three group meetings was delivered. A mixed methods study was completed which collected quantitative and qualitative data in the form of pre- and post-course questionnaires and focus group discussions.

Findings
Participants reported increased understanding, changed attitudes and better communication between clinicians and managers following the PLP. Self-rated knowledge increased across all domains but was only statistically significant for ability to engage, ability to establish shared goals and knowledge of decision-making processes.

Research limitations/implications
This paper highlights the value of paired learning in encouraging collaboration between clinicians and managers but is of a small size. The PLP did not provide enough data to examine relationships and interaction between clinicians and managers, this should be considered in any future work.

Originality/value
To the authors’ knowledge, this is the only published paper showing data from a PLP involving multi-disciplinary health professionals.
Empirical investigation of relationship patterns between competitive advantage and superior performance
Authors: Sigalas Christos , Papadakis Vassilis M. 
Published: January 2018

PurposeThe purpose of this paper is to empirically investigate the relationship patterns between competitive advantage and superior performance.Design/methodology/approachThis study empirically investigates the aforementioned relationship patterns using a cross-sectional, self-administered survey methodology.FindingsThe results indicate that there are four relationship patterns between competitive advantage and superior performance. In addition, this study provides empirical evidence of the reasons, underpinning the relationship pattern of competitive advantage without superior performance as well as the relationship pattern of superior performance without competitive advantage.Research limitations/implicationsThis study contributes to our knowledge that competitive advantage is neither a necessary nor a sufficient condition for superior performance.Practical implicationsIn finding support that there can be cases of underperformance despite competitive advantage and superior performance despite the absence of competitive advantage, the study’s findings are useful to practicing managers involved in the strategic management process of their firms.Originality/valueThis study fills an important gap in the empirical research, by responding to the literature call to test the possible relationship patterns between competitive advantage and superior performance. In addition, this study formally introduces the relationship pattern of competitive advantage without superior performance, and the relationship pattern of superior performance without competitive advantage that until now were largely ignored by the existing literature in the field of strategic management.