bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular phylogeny ofOdontosyllis(Annelida, Syllidae): A recent and rapid radiation of marine bioluminescent worms
Authors: Verdes Aida , Alvarez-Campos Patricia , Nygren Arne , Martin Guillermo San , Rouse Greg , Deheyn Dimitri D. , Gruber David F. , Holford Mande
Published: January 2018

Marine worms of the genusOdontosyllis(Syllidae, Annelida) are well known for their spectacular bioluminescent courtship rituals. During the reproductive period, the benthic marine worms leave the ocean floor and swim to the surface to spawn, using bioluminescent light for mate attraction. The behavioral aspects of the courtship ritual have been extensively investigated, but little is known about the origin and evolution of light production inOdontosyllis, which might in fact be a key factor shaping the natural history of the group, as bioluminescent courtship might promote speciation. To investigate the speciation patterns and evolutionary history ofOdontosyllisand to trace the origin of bioluminescence within the group, we inferred phylogenies using both gene concatenation and multispecies coalescent species-tree approaches with a multilocus molecular dataset (18SrRNA, 16SrRNAand COI). We also used this dataset to estimate divergence times and diversification rates in a relaxed molecular clock Bayesian framework. Our results suggest thatOdontosyllishas undergone a recent rapid radiation, possibly triggered by the origin of bioluminescent courtship, which might have increased speciation rates and lineage divergence through sexual selection. Additionally, our analyses reveal that the genusOdontosyllisas currently delineated is a paraphyletic group that needs to be reorganized to reflect evolutionary relationships.
Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease
Authors: Fernández Maria Victoria , Budde John , Del-Aguila Jorge , Ibañez Laura , Deming Yuetiva , Harari Oscar , Norton Joanne , Morris John C , Goate Alison ,   NIA-LOAD family study group,   NCRAD, Cruchaga Carlos
Published: January 2018

Gene-based tests to study the combined effect of rare variants towards a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially for complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We have examined the performance of several collapsing, variance-component and transmission disequilibrium tests across eight different software and twenty-two models utilizing a cohort of 285 families (N=1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the studied phenotype with high confidence and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, MAS1L) as candidates genes for familial LOAD.
The chick caudo-lateral epiblast acts as a permissive niche for generating neuromesodermal progenitor behaviours
Authors: Baillie-Johnson Peter , Voiculescu Octavian , Hayward Penny , Steventon Benjamin
Published: January 2018

Neuromesodermal progenitors (NMps) are a population of bipotent progenitors that maintain competence to generate both spinal cord and paraxial mesoderm throughout the elongation of the posterior body axis. Recent studies have generated populations of NMp-like cells in culture and have been shown to differentiate to both neural and mesodermal cell fates when transplanted into either mouse or chick embryos. Here, we aim to compare the potential of mouse embryonic stem (ES) cell-derived progenitor populations to generate NMp behavior against both undifferentiated and differentiated populations. We define NMp behaviour as the ability of cells to i) contribute to a significant proportion of the anterior-posterior body axis, ii) enter into both posterior neural and somitic compartments and, iii) retain a proportion of the progenitor population within the posterior growth zone. We compare previously identified ES cell-derived NMp-like populations to undifferentiated mouse ES cells and find that they all display similar potentials to generate NMp behaviourin vivo. To assess whether this competence is lost upon further differentiation, we generated anterior and posterior embryonic cell types through the generation of 3D gastruloids and show that NMp competence is lost within the anterior (Brachyury negative) portion of the gastruloid. Taken together, this demonstrates that the chick caudo-lateral epiblast is a highly permissive environment for testing NMp competence and is therefore not suitable as a positive test of neuromesodermal progenitor identity(ie. specification). However, it does act as an appropriate system to test for the loss of NMp potential, and therefore offers insight as a functional test for the regulation of NMp competencein vivo.
Malaria during pregnancy and newborns outcome in an unstable transmission area in Brazil: a population-based record linkage study
Authors: Dombrowski Jamille Gregório , de Souza Rodrigo Medeiros , Mendes Silva Natércia Regina , Barateiro André , Epiphanio Sabrina , Gonçalves Lígia Antunes , Farias Marinho Cláudio Romero
Published: January 2018

Background

Malaria during pregnancy is one of the major causes of mortality in tropical regions, causing maternal anemia, intrauterine growth retardation, preterm birth, and low birth weight (LBW). The integration of the information systems is crucial to assess the dimension of gestational malaria in a wide and useful way, to improve decision making and maternal-child health.

Methods and Findings

An observational population-based study acquired information retrospectively from all live births that occurred between 2006 and 2014 in Cruzeiro do Sul (Acre, Brazil). Social and clinical data of the mother and newborn was extracted from the Information System of Live Births. Malaria episodes information was obtained from the Brazilian Epidemiological Surveillance Information System Malaria. A deterministic record linkage was performed to assess malaria impact on pregnancy. The studied population presented a malaria incidence of 8.9%, of which 63.9% infected byPlasmodium (P.) vivax.Reduction of newborns birth weight at term (small for gestational age (SGA) and LBW) has been found associated withP. vivaxinfection during pregnancy (SGA - OR 1.24, 95% CI 1.02-1.52, p=0.035; term LBW - OR 1.39, 95% CI 1.03-1.88, p=0.033). Additionally,P. falciparuminfection during pregnancy has been found to be associated with preterm births (OR 1.54, 95% CI 1.09-2.18, p=0.016), which is related with late preterm births (OR 1.59, 95% CI 1.11-2.27, p=0.011).

Conclusions

Despite the decrease of malaria cases during the evaluated period, we present evidence of the deleterious effects of gestational malaria in a low transmission area in the Amazonian region. Regardless ofPlasmodiumspecies, malaria during pregnancy poses a risk for newborns birth weight reduction, highlighting the impact thatP. vivaxhas on the fetus.

Funding

São Paulo Research Foundation - FAPESP/Brazil.
Deep Learning Based Proarrhythmia Analysis Using Field Potentials Recorded from Human Pluripotent Stem Cells Derived Cardiomyocytes
Authors: Golgooni Zeinab , Mirsadeghi Sara , Baghshah Mahdieh Soleymani , Ataee Pedram , Baharvand Hossein , Pahlavan Sara , Rabiee Hamid R.
Published: January 2018

Aim

An early characterization of drug-induced cardiotoxicity may be possible by combining comprehensive in vitro pro-arrhythmia assay and deep learning techniques. The goal of this study was to develop a deep learning method to automatically detect irregular beating rhythm as well as abnormal waveforms of field potentials in an in vitro cardiotoxicity assay using human pluripotent stem cell (hPSC) derived cardiomyocytes and multi-electrode array (MEA) system.

Methods and Results

We included field potential waveforms from 380 experiments which obtained by application of some cardioactive drugs on healthy and/or patient-specific induced pluripotent stem cells derived cardiomyocytes (iPSC-CM). We employed convolutional and recurrent neural networks, in order to develop a new method for automatic classification of field potential recordings without using any hand-engineered features. In the proposed method, a preparation phase was initially applied to split 60-second long recordings into a series of 5-second long windows. Thereafter, the classification phase comprising of two main steps was designed. In the first step, 5-second long windows were classified using a designated convolutional neural network (CNN). In the second step, the results of 5-second long window assessments were used as the input sequence to a recurrent neural network (RNN). The output was then compared to electrophysiologist-level arrhythmia (irregularity or abnormal waveforms) detection, resulting in 0.84 accuracy, 0.84 sensitivity, 0.85 specificity, and 0.88 precision.

Conclusion

A novel deep learning approach based on a two-step CNN-RNN method can be used for automated analysis of “irregularity or abnormal waveforms” in an in vitro model of cardiotoxicity experiments.
Fidaxomicin jamsM. tuberculosisRNA polymerase motions needed for initiation via RbpA contacts
Authors: Boyaci Hande , Chen James , Lilic Mirjana , Palka Margaret , Mooney Rachel Anne , Landick Robert , Darst Seth A. , Campbell Elizabeth A.
Published: January 2018

Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective againstMycobacterium tuberculosisRNAPin vitro, but clinical use of Fdx is limited to treatingClostridium difficileintestinal infections due to poor absorption. To enable structure-guided optimization of Fdx to treat tuberculosis, we report the 3.4 Å cryo-electron microscopy structure of a completeM. tuberculosisRNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin and explains its strong effect onM. tuberculosis. We present additional structures that define conformational states ofM. tuberculosisRNAP between the free apo-holenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on Fdx.
Neural substrates of navigational decision-making inDrosophilalarva anemotaxis
Authors: Jovanic Tihana , Truman James W. , Gershow Marc , Zlatic Marta
Published: January 2018

Small animals use sensory information to navigate their environment in order to reach more favorable conditions. in gradients of light, temperature, odors and CO2,Drosophilalarvae alternate periods of runs and turns, regulating the frequency size and direction of turns, to move in a favorable direction. Whether larvae use the same strategies when navigating in response to somatosensory input is unknown. Further, while many of the sensory neurons that mediate navigation behaviors have been described, where and how these navigational strategies are implemented in the central nervous system and controlled by neuronal circuit elements is not well known. Here we characterize for the first time the navigational strategies of Drosophila larvae in gradients of air-current speeds using high-throughput behavioral assays and quantitative behavioral analysis. We find that larvae extend runs towards favorable directions and shorten runs in unfavorable directions, and that larvae regulate both the direction and amplitudes of turns. These results suggest similar central decision-making mechanisms underlie navigation behaviors in somatosensory and other sensory modalities. By silencing the activity of individual neurons and very sparse expression patterns (2 or 3 neuron types), we further identify the sensory neurons and circuit elements in the ventral nerve cord and brain of the larva required for navigational decisions during anemotaxis. The phenotypes of these central neurons are consistent with a mechanism where the increase of the turning rate in unfavorable conditions and decrease in turning rate in favorable conditions are independently controlled. In addition, we find phenotypes that suggest that the decisions of whether and which way to turn are controlled independently. Our study reveals that different neuronal modules in the nerve cord and brain mediate different aspects of navigational decision making. The neurons identified in our screen provide a basis for future detailed mechanistic understanding of the circuit principles of navigational decisionmaking.
Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia
Authors: Wang Yuanyuan , Liu Miao , Ruan Yuxia , Chu Qiaoyun , Cui Yanfen , Chen Ceshi , Ying Guoguang , Li Binghui
Published: January 2018

Metabolic reprogramming extensively occurs in proliferating cancer cells. This phenomenon occurs highly heterogeneously, but its origin has remained unclear. Here we use a physicochemical concept of free electron potential (FEP) and its equation of state to profile metabolites. We demonstrate that FEP change between substrates and products exactly reflects electrons dissipated in a metabolic transformation. Based on the law of conservation of electron in chemical reactions, a function of FEP change for central metabolism in proliferating cells are further derived, and it can accurately predict metabolic behaviors under hypoxia by maximizing the cellular FEP change to consume electrons. Therefore, enabling electron transfer dictates metabolic reprogramming in hypoxic cells, which underlies the major findings in cancer metabolism and is supported by our experiments. Importantly, our model established on FEP helps to reveal a combination of promising targets to inhibit tumor growth under hypoxia by blocking electron consumption, and could also guide future studies on cancer metabolism under hypoxia.
Agricultural Pollution Risks Influence Microbial Ecology in Honghu Lake
Authors: Han Maozhen , Dsouza Melissa , Zhou Chunyu , Li Hongjun , Zhang Junqian , Chen Chaoyun , Yao Qi , Zhong Chaofang , Zhou Hao , Gilbert Jack A , Wang Zhi , Ning Kang
Published: January 2018

Background

Agricultural activities, such as stock-farming, planting industry, and fish aquaculture, can influence the physicochemistry and biology of freshwater lakes. However, the extent to which these agricultural activities, especially those that result in eutrophication and antibiotic pollution, effect water and sediment-associated microbial ecology, remains unclear.

Methods

We performed a geospatial analysis of water and sediment associated microbial community structure, as well as physicochemical parameters and antibiotic pollution, across 18 sites in Honghu lake, which range from impacted to less-impacted by agricultural pollution. Furthermore, the co-occurrence network of water and sediment were built and compared accorded to the agricultural activities.

Results

Physicochemical properties including TN, TP, NO3--N, and NO2--N were correlated with microbial compositional differences in water samples. Likewise, in sediment samples, Sed-OM and Sed-TN correlated with microbial diversity. Oxytetracycline and tetracycline concentration described the majority of the variance in taxonomic and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Finally, the structure of microbial co-associations was influenced by the eutrophication and antibiotic pollution.

Conclusion

These analyses of the composition and structure of water and sediment microbial communities in anthropologically-impacted lakes are imperative for effective environmental pollution monitoring. Likewise, the exploration of the associations between environmental variables (e.g. physicochemical properties, and antibiotics) and community structure is important in the assessment of lake water quality and its ability to sustain agriculture. These results show agricultural practices can negatively influence not only the physicochemical properties, but also the biodiversity of microbial communities associated with the Honghu lake ecosystem. And these results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu lake.
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

Sequential 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

UKMYC5 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

Multicellularity 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

Background

The 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.

Results

We 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.

Conclusions

MBD2 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

Hypermutable 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.

Importance

Herd 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

Speciation 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

Genotype 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

Variation 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

Accurate 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 STATEMENT

Microtubules 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

During 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 summary

We 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.
N-Oxide–N-oxide interactions and Cl...Cl halogen bonds in pentachloropyridine N-oxide: the many-body approach to interactions in the crystal state
Authors: Wzgarda-Raj Kinga , Rybarczyk-Pirek Agnieszka J. , Wojtulewski Sławomir , Palusiak Marcin
Published: January 2018

Pentachloropyridine N-oxide, C5Cl5NO, crystallizes in the monoclinic space group P21/c. In the crystal structure, molecules are linked by C—Cl...Cl halogen bonds into infinite ribbons extending along the crystallographic [100] direction. These molecular aggregates are further stabilized by very short intermolecular N-oxide–N-oxide interactions into herringbone motifs. Computations based on quantum chemistry methods allowed for a more detailed description of the N-oxide–N-oxide interactions and Cl...Cl halogen bonds. For this purpose, Hirshfeld surface analysis and the many-body approach to interaction energy were applied.
Tetraphenylphosphonium tetrakis(trimethylsilanolato)ferrate(III)
Authors: Hay Michael T. , Yennawar Hemant P.
Published: January 2018

The structure of tetraphenylphosphonium tetrakis(trimethylsilanolato)ferrate(III), [(C6H5)4P][Fe(OSi(CH3)3)4], has tetragonal (I-4) symmetry, and was refined as an inversion twin. It is an ionic compound consisting of a tetraphenylphosphonium cation and a tetrakis(trimethylsilanolato)ferrate(III) anion. The crystal structure comprises the two ionic species each centered on a -4 symmetry element and contributing a fourth of its structure to the asymmetric unit. Each is surrounded by counter-ions on all sides. The cation contains a central phosphorous atom bound to four phenyl groups in a tetrahedral arrangement, while the anion contains a central iron(III) atom tetrahedrally coordinated by four trimethylsilanolato ligands.
3-Benzyl-5,5-diphenylimidazolidine-2,4-dione
Authors: Guerrab Walid , Akrad Rachida , Ansar Mhammed , Taoufik Jamal , Mague Joel T. , Ramli Youssef
Published: January 2018

The asymmetric unit of the title compound, C22H18N2O2, consists of two independent molecules differing primarily in the orientation of the benzyl substituent. The two independent molecules are associated through complementary C—H...π interactions and are elaborated into corrugated sheets by paired N—H...O and C—H...O hydrogen bonds. Additional C—H...O hydrogen bonds bind the sheets together.
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

Purpose

The purpose of this paper is to empirically investigate the relationship patterns between competitive advantage and superior performance.

Design/methodology/approach

This study empirically investigates the aforementioned relationship patterns using a cross-sectional, self-administered survey methodology.

Findings

The 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/implications

This study contributes to our knowledge that competitive advantage is neither a necessary nor a sufficient condition for superior performance.

Practical implications

In 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/value

This 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.
Cost saving allocation of horizontal cooperation in restructured natural gas distribution network
Authors: Razmi Jafar , Hassani Anis , Hafezalkotob Ashkan
Published: January 2018

Purpose

Over the past two decades, in developed countries a trend towards the liberalization and restructuring of the gas market has been observed. Today, restructuring is an ongoing process. In this study, a restructured natural gas market has been considered in which several regional distribution companies have ownership of the network and are competing against each other to gain more benefits. The main purpose of this study is to achieve efficiency and economic rationality in such a market through horizontal cooperation.

Design/methodology/approach

A restructured natural gas distribution network is modeled as a cooperative game to estimate the potential cost savings for various collaboration scenarios. In addition, the cost savings’ allocation among collaborating companies is evaluated using the cooperative game theory.

Findings

The results reveal validity and efficiency of the solution of the proposed model and capabilities of the cooperative game theory for reduction in gas distribution costs and improvement in the service level.

Research limitations/implications

This study is limited to natural gas in one region of Yazd City in Iran. Moreover, one segment of the natural gas network (i.e. distribution network) is modeled. Moreover, long-term cooperation between companies relies on fair distribution of cooperation benefits to the participants.

Practical implications

For the purpose of comparison and to get an insight into properties of the cost savings game, the real case study of one region of Yazd city in Iran is implemented.

Originality/value

This study contributes to the competitive models in the restructured gas market, particularly, in gas distribution network. The main contribution is to provide potential benefits for the participants via the horizontal cooperation.
A model for examining the factors impacting the near field communication technology adoption in the organizations
Authors: Museli Amir , Jafari Navimipour Nima
Published: January 2018

Purpose

Organizations are social entities comprising multiple people that are goal-directed and have coordinated activities that are also linked to the external environment. As information technology improves, the organizational performance is also improved and it results in positive changes and development in the organizations. Near field communication (NFC) is one of such technologies that can be implemented and utilized in an organization. The purpose of this paper is to investigate the important variables impacting the adoption of NFC in organizations and propose an applicable model for it.

Design/methodology/approach

In this paper, to have a successful NFC implementation in organizations and analyze main factors impacting the NFC technology adoption in organizations, a technology acceptance model-based approach is used.

Findings

The findings show that the main variables impacting NFC adoption are ease of use, potential risk, usefulness and cost. The obtained results indicate that the model has adequate and sufficient reliability, convergent validity and discriminant validity.

Originality/value

In this paper, the factors impacting the NFC adoption in organizations are pointed out, and the proposed model is tested on samples gathered from Azerbaijan railway employees and for statistical analysis of questionnaires, the SMART-PLS 2.0 software package is used.
Dark motives-counterfeit selling framework
Authors: Quach Sara , Thaichon Park
Published: January 2018

Purpose

The purpose of this paper is to explore the motives of online sellers of counterfeit products in online social networking sites.

Design/methodology/approach

The study uses a sample of 22 in-depth interviews with counterfeit sellers.

Findings

Based on the findings, the authors have developed a framework called “Dark motives-counterfeit selling.” The framework includes ten motives for selling online counterfeit products organized into four main themes. Personal characteristics include self-interest priority and sense of adventure. Moral justifications consist of denial of responsibility, and inequality hypothesis of self-deception process, and social acceptance. Operational aspects include: low-cost investment, free riding on luxury brands’ marketing effort, and invisibility from regulators. Finally, relationship management involves projecting image using volitional cues and interpersonal relationship with buyers. The themes regarding personal characteristics and morality are associated with their choice of counterfeit business. The other two themes are associated with the use of social networking sites for counterfeit business. Finally, some outcomes of online counterfeit retailing were revealed as value creation for the counterfeit buyers and value destruction for genuine brands’ customers.

Originality/value

This study investigates different rationalization strategies and motives behind selling counterfeit products with a special focus on online platforms. This is among the first to investigate the perspectives of counterfeit retailers in social network sites.