bluuebunny/crossref_metadata_2025 huggingface dataset:
Exact mapping of Illumina blind spots in theMycobacterium tuberculosisgenome reveals platform-wide and workflow-specific biases
Authors: Modlin Samuel J. , Robinhold Cassidy , Morrissey Christopher , Mitchell Scott N. , Ramirez-Busby Sarah M. , Shmaya Tal , Valafar Faramarz
Published: March 2020

Whole genome sequencing (WGS) is fundamental toM. tuberculosisbasic research and many clinical applications. Coverage across Illumina-sequencedM. tuberculosisgenomes is known to vary with sequence context, but this bias is poorly characterized. Here, through a novel application of phylogenomics that distinguishes genuine coverage bias from deletions, we discern Illumina “blind spots” in theM. tuberculosisreference genome for seven sequencing workflows. We find blind spots to be widespread, affecting 529 genes, and provide their exact coordinates, enabling salvage of unaffected regions. Fifty-seven PE/PPE genes (the primary families assumed to exhibit Illumina bias) lack blind spots entirely, while remaining PE/PPE genes account for 55.1% of blind spots. Surprisingly, we find coverage bias persists in homopolymers as short as 6 bp, shorter tracts than previously reported. While GC-rich regions challenge all Illumina sequencing workflows, a modified Nextera library preparation that amplifies DNA with a high-fidelity polymerase markedly attenuates coverage bias in GC-rich and homopolymeric sequences, expanding the “Illumina-sequencable” genome. Through these findings, and by defining workflow-specific exclusion criteria, we spotlight effective strategies for handling bias inM. tuberculosisIllumina WGS. This empirical analysis framework may be used to systematically evaluate coverage bias in other species using existing sequencing data.
Phenotypic Shifts in Neurons of the Dorsal Motor Nucleus of the Vagus Resulting from Chronic Cardiac Ischemia
Authors: Gorky Jonathan , Vadigepalli Rajanikanth , Schwaber James
Published: March 2020

Heart disease remains the number one cause of mortality in the world in spite of significant efforts aimed at treatment. The use of vagal stimulation in the treatment of heart failure has shown mixed successes (Dicarlo et al. 2013; Zannad et al. 2015), suggesting that the treatment has potential, but that the mechanism incompletely understood. Vagal activity confers a robust cardioprotective effect in both humans and animal models, preferentially originating specifically from the dorsal motor nucleus of the vagus (DMV) and deriving a significant benefit from intact gut projections, not just cardiac (Shinlapawittayatorn et al. 2013; Mastitskaya et al. 2012; Basalay et al. 2012). In order to examine the DMV response to heart failure, myocardial infarction was induced in male Sprague Dawley rats. DMV neurons were isolated in small pools of single cells using laser capture microdissection 1 week and 3 weeks after infarction and their gene expression assayed. The results show a transcriptional shift towards a neurosecretory phenotype starting at 1 week and increasing in recruitment of neurons to 3 weeks. The LAD ligation shift appears mediated in part by upregulation of Pax4a, a transcription factor most active during stem cell development of neurosecretory cells during embryonic development. This phenotype is characterized by upregulation of Cacna1d (Cav1.3) and Hcn2 along with increased expression of Cck and Sst. This work suggests that the neurons of the DMV adaptively respond to the dynamics present in the periphery, elucidating the means by which the nature of vagal activity responds to heart failure.

Significance Statement

The autonomic nervous system plays a significant role in the pathogenesis of cardiovascular disease. Through demonstration of shifting neuronal phenotypes in central neurons in response to peripheral stimuli, we suggest that neuron peptide or neurotransmitter phenotypes are not static in adult rodents. This suggests that even “reflexes” are modifiable dynamic systems. With such plasticity in the transcriptional programming existing in autonomic brain regions there can be new potential therapeutic interventions for cardiovascular disease aimed at leveraging the autonomic nervous system.
A dual-mechanism antibiotic targets Gram-negative bacteria and avoids drug resistance
Authors: Martin James K. , Wilson Maxwell Z. , Moore Gabriel M. , Sheehan Joseph P. , Mateus André , Li Sophia Hsin-Jung , Bratton Benjamin P. , Kim Hahn , Rabinowitz Joshua D. , Typas Athanasios , Savitski Mikhail M. , Gitai Zemer
Published: March 2020

The rise of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis. Of particular concern, no new antibiotic classes have been approved for treating Gram-negative pathogens in decades. Here, we characterize a compound, SCH-79797, that kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism of action (MoA) with undetectably low resistance frequencies. In an animal host model, SCH-79797 reduces pathogenesis ofAcinetobacter baumannii, a drug-resistant Gram-negative pathogen. To characterize the MoA of SCH-79797 we combined quantitative imaging, proteomic, genetic, metabolomic, and cell-based assays. This pipeline shows that SCH-79797 has two independent cellular targets, folate metabolism and bacterial membrane integrity, and outperforms combination treatments with other antifolates and membrane disruptors in killing MRSA persisters. Thus, SCH-79797 represents a promising lead antibiotic and suggests that combining multiple MoAs onto a single chemical scaffold may be an underappreciated approach to target challenging bacterial pathogens.
Filtering Variables for Supervised Sparse Network Analysis
Authors: Towle-Miller Lorin M. , Miecznikowski Jeffrey C. , Zhang Fan , Tritchler David L.
Published: March 2020

Motivation

We present a method for dimension reduction designed to filter variables or features such as genes considered to be irrelevant for a downstream analysis designed to detect supervised gene networks in sparse settings. This approach can improve interpret-ability for a variety of analysis methods. We present a method to filter genes and transcripts prior to network analysis. This method has applications in a setting where the downstream analysis may include sparse canonical correlation analysis.

Results

Filtering methods specifically for cluster and network analysis are introduced and compared by simulating modular networks with known statistical properties. Our proposed method performs favorably eliminating irrelevant features but maintaining important biological signal under a variety of different signal settings. We show that the speed and accuracy of methods such as sparse canonical correlation are increased after filtering, thus greatly improving the scalability of these approaches.

Availability

Code for performing the gene filtering algorithm described in this manuscript may be accessed through the geneFiltering R package available on Github athttps://github.com/lorinmil/geneFiltering. Functions are available to filter genes and perform simulations of a network system. For access to the data used in this manuscript, contact corresponding author.

Contact

lorinmil@buffalo.edu,jcm38@buffalo.edu,fzhang8@buffalo.edu, anddlt6@buffalo.edu
Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis
Authors: Harris Lachlan , Rigo Piero , Stiehl Thomas , Gaber Zachary , Austin Sophie H. L. , del Mar Masdeu Maria , Edwards Amelia , Urbán Noelia , Marciniak-Czochra Anna , Guillemot François
Published: March 2020

Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilise during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this reduction in stem cell depletion rate is the result of multiple coordinated changes in stem cell behaviour. In particular, while active neural stem cells divide only once or twice before differentiating rapidly in juveniles, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomic, mathematical modelling and label-retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These progressive changes in stem cell behaviour result from reduced expression of the pro-activation protein ASCL1 due to increased post-translational degradation. These mechanisms help reconcile current contradictory models of hippocampal NSC dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species including humans.
Rapid changes in brain activity during learning of grapheme-phoneme associations in adults
Authors: Xu Weiyong , Kolozsvari Orsolya Beatrix , Oostenveld Robert , Hämäläinen Jarmo Arvid
Published: March 2020

Learning to associate written letters with speech sounds is crucial for the initial phase of acquiring reading skills. However, little is known about the cortical reorganization for supporting letter-speech sound learning, particularly the brain dynamics during the learning of grapheme-phoneme associations. In the present study, we trained 30 Finnish participants (mean age: 24.33 years, SD: 3.50 years) to associate novel foreign letters with familiar Finnish speech sounds on two consecutive days (first day ~ 50 minutes; second day ~ 25 minutes), while neural activity was measured using magnetoencephalography (MEG). Two sets of audiovisual stimuli were used for the training in which the grapheme-phoneme association in one set (Learnable) could be learned based on the different learning cues provided, but not in the other set (Control). The learning progress was tracked at a trial-by-trial basis and used to segment different learning stages for the MEG source analysis. The learning-related changes were examined by comparing the brain responses to Learnable and Control uni/multi-sensory stimuli, as well as the brain responses to learning cues at different learning stages over the two days. We found dynamic changes in brain responses related to multi-sensory processing when grapheme-phoneme associations were learned. Further, changes were observed in the brain responses to the novel letters during the learning process. We also found that some of these learning effects were observed only after memory consolidation the following day. Overall, the learning process modulated the activity in a large network of brain regions, including the superior temporal cortex and the dorsal (parietal) pathway. Most interestingly, middle- and inferior-temporal regions were engaged during multi-sensory memory encoding after the cross-modal relationship was extracted from the learning cues. Our findings highlight the brain dynamics and plasticity related to the learning of letter-speech sound associations and provide a more refined model of grapheme-phoneme learning in reading acquisition.
Site-specific machine learning predictive fertilization models for potato crops in Eastern Canada
Authors: Coulibali Zonlehoua , Cambouris Athyna Nancy , Parent Serge-Étienne
Published: March 2020

1

Statistical modeling is commonly used to relate the performance of potato (Solanum tuberosumL.) to fertilizer requirements. Prescribing optimal nutrient doses is challenging because of the involvement of many variables including weather, soils, land management, genotypes, and severity of pests and diseases. Where sufficient data are available, machine learning algorithms can be used to predict crop performance. The objective of this study was to predict tuber yield and quality (size and specific gravity) as impacted by nitrogen, phosphorus and potassium fertilization as well as weather, soils and land management variables. We exploited a data set of 273 field experiments conducted from 1979 to 2017 in Quebec (Canada). We developed, evaluated and compared predictions from a hierarchical Mitscherlich model,k-nearest neighbors, random forest, neuronal networks and Gaussian processes. Machine learning models returned R2values of 0.49–0.59 for tuber marketable yield prediction, which were higher than the Mitscherlich model R2(0.37). The models were more likely to predict medium-size tubers (R2= 0.60–0.69) and tuber specific gravity (R2= 0.58–0.67) than large-size tubers (R2= 0.55–0.64) and marketable yield. Response surfaces from the Mitscherlich model, neural networks and Gaussian processes returned smooth responses that agreed more with actual evidence than discontinuous curves derived fromk-nearest neighbors and random forest models. When marginalized to obtain optimal dosages from dose-response surfaces given constant weather, soil and land management conditions, some disagreements occurred between models. Due to their built-in ability to develop recommendations within a probabilistic risk-assessment framework, Gaussian processes stood out as the most promising algorithm to support decisions that minimize economic or agronomic risks.
Varicella zoster virus encodes a viral decoy RHIM to inhibit cell death
Authors: Steain Megan , Baker Max O.D.G. , Pham Chi L.L. , Gambin Yann , Sierecki Emma , McSharry Brian P. , Avdic Selmir , Slobedman Barry , Sunde Margaret , Abendroth Allison
Published: March 2020

Herpesviruses are known to encode a number of inhibitors of host cell death, including Rip Homotypic Interaction Motif (RHIM)-containing proteins. Varicella zoster virus (VZV) is a member of the alphaherpesvirus subfamily and is responsible for causing chickenpox and shingles. We have identified a novel viral RHIM in the VZV capsid triplex protein open reading frame (ORF) 20 that acts as a host cell death inhibitor. Like the human cellular RHIMs in RIPK1 and RIPK3 that stabilise the necrosome in TNF-induced necroptosis, and the viral RHIM in M45 from murine cytomegalovirus that inhibits cell death, the ORF20 RHIM is capable of forming fibrillar functional amyloid complexes. Notably, the ORF20 RHIM forms hybrid amyloid complexes with human ZBP1, a cytoplasmic sensor of viral nucleic acid. Although VZV can inhibit TNF-induced necroptosis, the ORF20 RHIM does not appear to be responsible for this inhibition. In contrast, the ZBP1 pathway is identified as important for VZV infection. Mutation of the ORF20 RHIM renders the virus incapable of efficient spread in ZBP1-expressing HT-29 cells, an effect which can be reversed by the inhibition of caspases. Therefore we conclude that the VZV ORF20 RHIM is important for preventing ZBP1-driven apoptosis during VZV infection, and propose that it mediates this effect by sequestering ZBP1 into decoy amyloid assemblies.

Author Summary

Rip homotypic interaction motifs (RHIMs) are found in host proteins that can signal for programmed cell death and in viral proteins that can prevent it. Complexes stabilized by intermolecular interactions involving RHIMs have a fibrillar amyloid structure. We have identified a novel RHIM within the ORF20 protein expressed by Varicella zoster virus (VZV) that forms amyloid-based complexes with human cellular RHIMs. Whereas other herpesvirus RHIMs inhibit TNF-driven necroptosis, this new VZV RHIM targets the host RHIM-containing protein ZBP1 to inhibit apoptosis during infection. This is the first study to demonstrate the importance of the ZBP1 pathway in VZV infection and to identify the role of a viral RHIM in apoptosis inhibition. It broadens our understanding of host defense pathways and demonstrates how a decoy amyloid strategy is employed by pathogens to circumvent the host response.
Major stages of vertebrate adaptive radiation are assembled from a disparate spatiotemporal landscape
Authors: Richards Emilie J. , McGirr Joseph A. , Wang Jeremy R. , St. John Michelle E. , Poelstra Jelmer W. , Solano Maria J. , O’Connell Delaney C. , Turner Bruce J. , Martin Christopher H.
Published: March 2020

To investigate the origins and stages of vertebrate adaptive radiation, we reconstructed the spatial and temporal histories of genetic variants underlying major phenotypic axes of diversification from the genomes of 202 Caribbean pupfishes. Ancient standing variation from disparate spatial sources was reassembled into new combinations which are under strong selection for adaptation to novel trophic niches on only a single island throughout the Caribbean. This occurred in three stages: first, standing variation associated with feeding behavior swept, then standing variation regulating craniofacial development and pigmentation, and finally de novo variation for craniofacial development. Our results provide clear support for two longstanding hypotheses about adaptive radiation and demonstrate how ancient alleles maintained for millennia in distinct environmental refugia can be assembled into new adaptive combinations.

One Sentence Summary

Ancient origins of adaptive radiation
Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms
Authors: McNee Adam , Smith Trevor , Holzer Barbara , Clark Becky , Bessell Emily , Guibinga Ghiabe , Brown Heather , Schultheis Katherine , Fisher Paul , Ramos Stephanie , Nunez Alejandro , Bernard Matthieu , Martini Veronica , Chrun Tiphany , Xiao Yongli , Kash John C. , Taubenberger Jeffery K. , Elliott Sarah , Patel Ami , Beverley Peter , Rijal Pramila , Weiner David , Townsend Alain , Broderick Kate , Tchilian Elma
Published: March 2020

Monoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.
Targeted mutagenesis of Δ5 and Δ6 fatty acyl desaturases induce multiplex-mutagenesis and lipogenesis in Atlantic salmon (Salmo salar)
Authors: Jin Yang , Datsomor Alex K. , Olsen Rolf E. , Vik Jon Olav , Torgersen Jacob S. , Edvardsen Rolf B. , Wargelius Anna , Winge Per , Grammes Fabian
Published: March 2020

With declining wild fish populations, farmed Atlantic salmon (Salmo salar) has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA) including 20:5n-3 and 22:6n-3. However, the introduction of plant-based oil in fish diets has reduced the content of these beneficial LC-HUFA. The capability of biosynthesis of LC-HUFAs depends on fatty acids supplied in diets and the genetic potential residing in the fish. Key proteins involved in LC-HUFA synthesis in salmon include fatty acid desaturases 2 (Fads2). In a recent study we used CRISPR/Cas9 to generate two F0 mutant strains of salmon, 1)Δ6abc/5Mtwith mutations inΔ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-cgenes, and 2)Δ6bcMtwith mutations inΔ6fads2-b and Δ6fads2-cgenes. The CRISPR mutated salmon (crispants) had reduced levels of LC-HUFA and expression of targetedfads2genes. In present study we apply whole transcriptome analysis on thesefads2crispants. Our purpose is to evaluate the genetic mosaicism infads2crispants and the effect these mutations had on other lipid metabolism pathways in fish. BothΔ6abc/5MtandΔ6bcMtcrispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. Skipping of a CRISPR-targeted exon was observed inΔ6fads2-agene ofΔ6abc/5Mtsalmon. TheΔ6abc/5Mtfish also displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation ofsrebp1genes as well as genes involved in fatty acidde-novosynthesis, fatty acidβ-oxidation and lipogenesis. Bothelovl5andelovl2genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation ofΔ6bcMtsurprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability.
Molecular resolution imaging by post-labeling expansion single-molecule localization microscopy (Ex-SMLM)
Authors: Zwettler Fabian U. , Reinhard Sebastian , Gambarotto Davide , Bell Toby D. M. , Hamel Virginie , Guichard Paul , Sauer Markus
Published: March 2020

Expansion microscopy (ExM) enables super-resolution fluorescence imaging of physically expanded biological samples with conventional microscopes. By combining expansion microscopy (ExM) with single-molecule localization microscopy (SMLM) it is potentially possible to approach the resolution of electron microscopy. However, current attempts to combine both methods remained challenging because of protein and fluorophore loss during digestion or denaturation, gelation, and the incompatibility of expanded polyelectrolyte hydrogels with photoswitching buffers. Here we show that re-embedding of expanded hydrogels enablesdSTORM imaging of expanded samples and demonstrate that post-labeling ExM resolves the current limitations of super-resolution microscopy. Using microtubules as a reference structure and centrioles, we demonstrate that post-labeling Ex-SMLM preserves ultrastructural details, improves the labeling efficiency and reduces the positional error arising from linking fluorophores into the gel thus paving the way for super-resolution imaging of immunolabeled endogenous proteins with true molecular resolution.
Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size
Authors: Buenzli Pascal R. , Lanaro Matthew , Wong Cynthia S. , McLaughlin Maximilian P. , Allenby Mark C. , Woodruff Maria A. , Simpson Matthew J.
Published: March 2020

Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction–diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction–diffusion models of cells that have robust, consistent behaviours.
HisTrader: A Tool to Identify Nucleosome Free Regions from ChIP-Seq of Histone Post-Translational Modifications
Authors: Yan Yifei , Gnanapragasam Ansley , Bailey Swneke
Published: March 2020

Motivation

Chromatin immuno-precipitation sequencing (ChIP-Seq) of histone post-translational modifications coupled withde novomotif elucidation and enrichment analyses can identify transcription factors responsible for orchestrating transitions between cell-and disease-states. However, the identified regulatory elements can span several kilobases (kb) in length, which complicates motif-based analyses. Restricting the length of the target DNA sequence(s) can reduce false positives. Therefore, we present HisTrader, a computational tool to identify the regions accessible to transcription factors, nucleosome free regions (NFRs), within histone modification peaks to reduce the DNA sequence length required for motif analyses.

Results

HisTrader accurately identifies NFRs from H3K27Ac ChIP-seq profiles of the lung cancer cell line A549, which are validated by the presence of DNaseI hypersensitivity. In addition, HisTrader reveals that multiple NFRs are common within individual regulatory elements; an easily overlooked feature that should be considered to improve sensitivity of motif analyses using histone modification ChIP-seq data.

Availability and implementation

The HisTrader script is open-source and available on GitHub (https://github.com/SvenBaileyLab/Histrader) under a GNU general public license (GPLv3). HisTrader is written in PERL and can be run on any platform with PERL installed.
Autofluorescence imaging of 3D tumor-macrophage microscale cultures resolves spatial and temporal dynamics of macrophage metabolism
Authors: Heaster Tiffany M. , Humayun Mouhita , Yu Jiaquan , Beebe David J. , Skala Melissa C.
Published: March 2020

Macrophages within the tumor microenvironment (TME) exhibit a spectrum of pro-tumor and anti-tumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to non-destructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours post-stimulation for mouse macrophages (RAW 264.7) stimulated with IFN-γ or IL-4 plus IL-13 in 2D culture, validating that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse PyVMT or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor co-cultures exhibited significantly different FAD mean lifetimes and greater migration than mono-cultures at 24, 48, and 72 hours post-seeding. In co-cultures with primary human cancer cells, actively-migrating monocyte-derived macrophages had greater redox ratios (NAD(P)H/FAD intensity) compared to passively-migrating monocytes at 24 and 48 hours post-seeding, reflecting metabolic heterogeneity in this sub-population of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor-immune crosstalk within the 3D TME.
A faster and more accurate algorithm for calculating population genetics statistics requiring sums of Stirling numbers of the first kind
Authors: Chen Swaine L. , Temme Nico M.
Published: March 2020

Stirling numbers of the first kind are used in the derivation of several population genetics statistics, which in turn are useful for testing evolutionary hypotheses directly from DNA sequences. Here, we explore the cumulative distribution function of these Stirling numbers, which enables a single direct estimate of the sum, using representations in terms of the incomplete beta function. This estimator enables an improved method for calculating an asymptotic estimate for one useful statistic, Fu’sFs. By reducing the calculation from a sum of terms involving Stirling numbers to a single estimate, we simultaneously improve accuracy and dramatically increase speed.
The Genetic Architecture of Leaf Stable Carbon Isotope Composition inZea maysand the Effect of Transpiration Efficiency on Elemental Accumulation
Authors: Sorgini Crystal A. , Roberts Lucas M. , Cousins Asaph B. , Baxter Ivan , Studer Anthony J.
Published: March 2020

With increased demand on freshwater resources for agriculture, it is imperative that more water-use efficient crops are developed. Leaf stable carbon isotope composition, δ13C, is a proxy for transpiration efficiency and a possible tool for breeders, but the underlying mechanisms effecting δ13C in C4plants are not known. It has been suggested that differences in specific leaf area, which potentially reflects variation in internal CO2diffusion, can impact leaf δ13C. However, at this point the relationship has not been tested in maize. Furthermore, although it is known that water movement is important for elemental uptake, it is not clear how manipulation of transpiration for increased water-use efficiency may impact nutrient accumulation. Here we characterize the underlying genetic architecture of leaf δ13C and test its relationship to specific leaf area and the ionome in four biparental populations of maize. Five significant QTL for leaf δ13C were identified, including both novel QTL as well as some that were identified previously in maize kernels. One of the QTL regions contains an Erecta-like gene, the ortholog of which has been shown to regulate transpiration efficiency and leaf δ13C inArabidopsis. Our data does not support a relationship between δ13C and specific leaf area, and of the 19 elements analyzed, only a weak correlation between molybdenum and δ13C was detected. Together these data begin to build a genetic understanding of leaf δ13C in maize and suggest the potential to improve plant water use without significantly influencing elemental homeostasis.

Article Summary

Quantitative genetics approaches were used to investigate the genetic architecture of leaf stable carbon isotope discrimination (δ13C) in maize. Developing a better understanding of leaf δ13C could facilitate its use in breeding for reduced transpirational water loss. Several genomic regions were identified that contribute to the variation observed in leaf δ13C. Furthermore, contrary to what has been observed in other species, leaf δ13C was not correlated with specific leaf area. Finally, a leaf ionomic analysis indicates that a reduction in transpiration, and thus mass flow, would not result in a decrease in nutrient accumulation.
Preprocessing choices affect RNA velocity results for droplet scRNA-seq data
Authors: Soneson Charlotte , Srivastava Avi , Patro Rob , Stadler Michael B
Published: March 2020

Experimental single-cell approaches are becoming widely used for many purposes, including investigation of the dynamic behaviour of developing biological systems. Consequently, a large number of computational methods for extracting dynamic information from such data have been developed. One example is RNA velocity analysis, in which spliced and unspliced RNA abundances are jointly modeled in order to infer a ‘direction of change’ and thereby a future state for each cell in the gene expression space.

Naturally, the accuracy and interpretability of the inferred RNA velocities depend crucially on the correctness of the estimated abundances. Here, we systematically compare four widely used quantification tools, in total yielding twelve different quantification approaches, in terms of their estimates of spliced and unspliced RNA abundances in four experimental droplet scRNA-seq data sets. We show that there are substantial differences between the quantifications obtained from different tools, and identify typical genes for which such discrepancies are observed. We further show that these abundance differences propagate to the downstream analysis, and can have a large effect on estimated velocities as well as the biological interpretation.

Our results highlight that abundance quantification is a crucial aspect of the RNA velocity analysis workflow, and that both the definition of the genomic features of interest and the quantification algorithm itself require careful consideration.
Quantitative phase analysis of slag hydrating in an alkaline environment
Authors: Reddy K. Chiranjeevi , Subramaniam Kolluru V. L.
Published: March 2020

An X-ray diffraction (XRD)-based evaluation of the crystalline and amorphous phases in slag hydrating in an alkaline environment is presented. A method is developed for the quantification of the amorphous phases present in hydrating slag in a sodium hydroxide solution. In hydrating slag, the amorphous reaction product is identified as calcium aluminosilicate hydrate. A water-soluble sodium-based amorphous reaction product is also produced. The XRD-based quantification method relies on the direct decomposition of the XRD intensity pattern of the total amorphous phase present in partially hydrated slag into the intensity patterns of the amorphous unreacted slag, the hydrate and the sodium-based product. The unreacted slag content in partially hydrated slag is also determined from the decomposition of the intensity signature of the total amorphous phase. An independent verification of the amorphous unreacted slag content in hydrating slag is obtained from measurements of blends of unhydrated and partially hydrated slag. The XRD-based phase-quantification procedure developed here provides a basis for evaluating the extent of reaction in hydrating slag.
PtychoShelves, a versatile high-level framework for high-performance analysis of ptychographic data
Authors: Wakonig Klaus , Stadler Hans-Christian , Odstrčil Michal , Tsai Esther H. R. , Diaz Ana , Holler Mirko , Usov Ivan , Raabe Jörg , Menzel Andreas , Guizar-Sicairos Manuel
Published: March 2020

Over the past decade, ptychography has been proven to be a robust tool for non-destructive high-resolution quantitative electron, X-ray and optical microscopy. It allows for quantitative reconstruction of the specimen's transmissivity, as well as recovery of the illuminating wavefront. Additionally, various algorithms have been developed to account for systematic errors and improved convergence. With fast ptychographic microscopes and more advanced algorithms, both the complexity of the reconstruction task and the data volume increase significantly. PtychoShelves is a software package which combines high-level modularity for easy and fast changes to the data-processing pipeline, and high-performance computing on CPUs and GPUs.
Consumer ethics: insights from business professionals
Authors: Lo Lawrence W.T. , Chan Haksin , Tang Felix , Yeung Kwan-Yu
Published: March 2020

Purpose

This research aims to generate new insights into consumer ethics by tapping into business executives' first-hand experience. The overarching goal of this novel, discovery-oriented approach is to illuminate the interactive relationships between business and consumer ethics, and to offer contextualized insights into consumers' (un)ethical behaviors.

Design/methodology/approach

Three focus group interviews were conducted with senior business executives representing nine different industry sectors. Thematic analysis was performed to identify key themes for an integrative model.

Findings

Four key themes emerged, highlighting: (1) the mutual influence between business and consumer ethics, (2) the nature and intensity of consumer ethics, (3) the dual influence of digital communication, and (4) the partial influence of consumer education. The themes gave rise to an integrative conceptual model.

Research limitations/implications

This research was limited somewhat by the small and judgmental sample.

Practical implications

Consumers' growing demands for business ethics underscore the need for companies to elevate ethical considerations. The amplified consumer voice on social media is dreaded by business practitioners and is regarded as unethical consumer behavior to be actively managed.

Social implications

Business and consumer ethics can mutually influence each other in a benign or vicious circle. Consumer education is effective in some but not all domains.

Originality/value

Business practitioners' insights reveal (1) the interactivity of business and consumer ethics and (2) the diversity of (un)ethical consumer behaviors. They point to the need for an enriched definition of consumer ethics and an expansion on the categorical structure of consumers' (un)ethical practices.
Price stabilization or income support? Preferences and cost of programmes
Authors: Mahanta Amarjyoti , Sengupta Bodhisattva
Published: March 2020

Purpose

Over the past 25 years, direct cash transfers (often abbreviated as direct benefit transfer, DBT) to the poorer section of the society are gaining popularity over explicit subsidization of prices of essential commodities. One of the main arguments in favor of DBT is that it will cost the government less money and yet, the consumer benefit will be high. This paper aims to examine the proposition critically. Removal of price support exposes the consumers to market risk, and any income support programme must compensate the consumers accordingly.

Design/methodology/approach

The authors use a theoretical study where the model of a representative consumer under different specification of preferences is used to compare programme costs under price stabilization and income support programmes.

Findings

What the authors show in the paper that the comparative cost of the programmes crucially depends on the nature of preferences, as well as the good under question. For certain specifications of the indirect utility function and the marginal utility of money, one programme may cost less than the other. Any policymaker must take account of such nuances before making a blanket prescription.

Research limitations/implications

The main limitation is that only a representative consumer is taken.

Practical implications

The specification of indirect utility function plays a decisive role in deciding, which one these two policies, DBT or stabilizing price at a fixed level.

Originality/value

The main novelty of the paper is in the different specifications of the indirect utility function considered in the paper.
Festivals’ social impacts and emotional solidarity
Authors: Yozukmaz Nisan , Bertan Serkan , Alkaya Serap
Published: March 2020

Purpose

Interactions between local people and guests/visitors are the main elements of tourism experience. And local festivals, considered as a significant part of festival tourism, are quite important in this context. Though many studies have been conducted about interaction between local residents and guests tourists, emotional solidarity remains as a concept which has not yet been studied much in tourism literature on local festivals. The aim of this study is to examine emotional solidarity in tourism festival literature and to determine the relationships between perceptions of local people related to social impacts of festivals and emotional solidarity they feel for guests/visitors.

Design/methodology/approach

In line with this purpose, a quantitative approach was adopted, and 19th weaving, culture and handicrafts festival held in Buldan was chosen to be studied as it is an important festival for local people dwelling in Buldan, Denizli province located in Aegean Region in Turkey. The study data were obtained through questionnaire method conducted with Buldan residents during the 19th festival (June, 28th–30th, 2019). The sample was determined with random sampling method.

Findings

The data were analyzed via factor and regression analyses. As a result of factor analysis, social impacts of the festivals were grouped under 6 factors (under 3 subfactors of social benefits: communal benefits, cultural–educational benefits, social unity benefits; under 3 subfactors of social costs: concerns related to social resources, concerns related to life quality and concerns related to social order).

Practical implications

Local people's perceptions of social impacts of festivals must be determined in order to find their impacts on emotional solidarity, and deficiencies must be remedied. Local governments who organize festivals to invigorate local economies usually try to attract more visitors with the purpose of maximizing economic impacts of festivals, and this is done without placing much importance on the social problems and social change that may arise in the future (Crandall, 1994).

Originality/value

Relationships were determined between emotional solidarity and residents' perceptions towards social and cultural–educational benefits as well as their concerns related to social resources and life quality.
Value of project management in university–industry R&D collaborations
Authors: Fernandes Gabriela , O' Sullivan David , Pinto Eduardo B. , Araújo Madalena , Machado Ricardo J.
Published: March 2020

Purpose

University–industry projects provide special challenges in understanding and expressing the values required of project management (PM) in delivering stakeholder benefits. This paper presents a framework for understanding, identifying and managing the values of PM in major university–industry R&D projects.

Design/methodology/approach

The value framework identifies for each of the key stakeholders, the key PM values that may require to be managed and are largely derived from research literature. Empirical research then explores, prioritises and selects key PM values that need to be managed for a specific project. A large case study is used involving one university and one industry collaborating on a multi-million Euro initiative over six years. Empirical research was conducted by researchers who observed at close quarters, the challenges and successes of managing the competing values of key stakeholders.

Findings

The value framework takes a stakeholders' perspective by identifying the respective PM values for each of six stakeholders: university–industry consortium, university, industry, R&D external entities, funding entity and society.

Research limitations/implications

The research was performed using only one case study which limits the generalisability of its findings; however, the findings are presented as a decision support aid for project consortia in developing values for their own collaboration.

Practical implications

Guidance and decision support are provided to multi-stakeholder research consortia when selecting values that need to be managed for achieving tangible and intangible project benefits.

Originality/value

The paper demonstrates a proposed framework for designing and managing the value of PM in large multi-stakeholder university–industry R&D projects.
Perceptions of social loafing during the process of group development
Authors: Zhu Min , Singh Satvir , Wang Huaqing
Published: March 2020

Purpose

The purpose of this paper is to extend the social loafing literature by investigating the role of group development process on perceptions of social loafing within groups. Building on extant literature, it is contended that group members’ association with the group development stages can help in predicting their perceptions of social loafing.

Design/methodology/approach

Using a cross-sectional survey data were collected from 164 individuals nested in 39 groups. Mixed-effect modeling in R was unitized to test the proposed hypotheses.

Findings

Results of mixed-effect modeling in R show that group development stage of inclusion and dependency (stage 1) has no significant effect on perceptions of social loafing. Whereas, group development stage of counterdependency and fight (stage 2) has positive, and trust and structure (stage 3) and work (stage 4) has negative effect on perception of social loafing by group members.

Originality/value

This study investigates unique relationships between group members’ association with different stages of group development and their perceptions of social loafing. Additionally, a newer, shorter and cost-effective scale to measure four stages of group development is developed.
How ethnic cultures influence practice-based learning
Authors: Lui Kwok Wah Ronnie , Choy Sarojni
Published: March 2020

Purpose

This paper aims to report on a study that used the practice theory lens to understand how Chinese ethnic culture influences restaurant workers' learning through engagement in everyday work practices.

Design/methodology/approach

A multiple case study approach was used. Data were collected from semi-structured interviews and site observations. Thematic analysis was conducted to identify how workers learnt the sayings, doings and relatings in their workplaces.

Findings

The findings show that the ethnic culture of the participants influences and enriches their learning in practice settings such as small Chinese restaurants.

Research limitations/implications

The understandings presented here need to be verified through more research in different regions and nations. In addition, cross-cultural studies on other ethnic restaurants may contribute to deeper understandings of the influences of ethnic culture on practice-based learning.

Social implications

The research contributes to understanding the influence of ethnic culture on practice-based learning.

Originality/value

The understandings gained from the findings of this study form a useful basis for curriculum development and instructional design of training programmes for practice-based as well as work-integrated-learning components of vocational curriculum. Furthermore, awareness of the strengths of the ethnic culture is of interest to owner/managers of small Chinese restaurants to afford supportive learning environments for workers.
Green supply chain management and innovation: a modern review
Authors: Carvalho Lucas Silvestre de , Stefanelli Nelson Oliveira , Viana Lilian Carolina , Vasconcelos Diogo de Siqueira Camargo , Oliveira Bruno Garcia
Published: March 2020

Purpose

This paper aims to investigate the main associations between research regarding innovation and green supply chain management (GSCM).

Design/methodology/approach

For this the study sought to (1) present the most cited authors in the area; (2) demonstrate the main localities that develop research with this focus; (3) list the main journals with the published research on the themes. The methodology used was a bibliometric survey using the Scopus database as the data source. The VOSviewer® software was used to perform the analysis of the database from the respective DOI® of each article.

Findings

As results of the research, it is possible to demonstrate the existence of an agglomeration of countries that are interrelated in the development of research on these themes, especially China, the United States and the United Kingdom as the main foundations of this center.

Originality/value

This paper evidences the direction of scientific research within the analyzed area, demonstrating where there is convergence for innovation in actions related to GSCM. This guidance may demonstrate possible existing and unexplored gaps so that researchers can direct future research or check gaps to be filled by the development of new processes.