bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational load, inbreeding depression and heterosis in subdivided populations
Authors: Charlesworth Brian 
Published: June 2018

AbstractThis paper examines the extent to which empirical estimates of inbreeding depression and inter-population heterosis in subdivided populations, as well as the effects of local population size on mean fitness, can be explained in terms of estimates of mutation rates, and the distribution of selection coefficients against deleterious mutations provided by population genomics data. Using results from population genetics models, numerical predictions of the genetic load, inbreeding depression and heterosis were obtained for a broad range of selection coefficients and mutation rates. The models allowed for the possibility of very high mutation rates per nucleotide site, as is sometimes observed for epiallelic mutations. There was fairly good quantitative agreement between the theoretical predictions and empirical estimates of heterosis and the effects of population size on genetic load, on the assumption that the deleterious mutation rate per individual per generation is approximately one, but there was less good agreement for inbreeding depression. Weak selection, of the order of magnitude suggested by population genomic analyses, is required to explain the observed patterns. Possible caveats concerning the applicability of the models are discussed.
Longitudinally Mapping Childhood Socioeconomic Status Associations with Cortical and Subcortical Morphology
Authors: McDermott Cassidy L. , Seidlitz Jakob , Nadig Ajay , Liu Siyuan , Clasen Liv S. , Blumenthal Jonathan D. , Reardon Paul Kirkpatrick , Lalonde François , Patel Raihaan , Chakravarty Mallar M. , Lerch Jason P. , Raznahan Armin 
Published: June 2018

AbstractChildhood socioeconomic status (SES) impacts cognitive development and mental health, but its association with structural brain development is not yet well-characterized. Here, we analyzed 1243 longitudinally-acquired structural MRI scans from 623 youth to investigate the relation between SES and cortical and subcortical morphology between ages 5 and 25 years. We found positive associations between SES and total volumes of the brain, cortical sheet, and four separate subcortical structures. These associations were developmentally fixed rather than age-dependent. Surface-based shape analysis revealed that higher SES is associated with areal expansion of (i) lateral prefrontal, anterior cingulate, lateral temporal, and superior parietal cortices and (ii) ventrolateral thalamic, and medial amygdalo-hippocampal sub-regions. Meta-analyses of functional imaging data indicate that cortical correlates of SES are centered on brain systems subserving sensorimotor functions, language, memory, and emotional processing. We further show that anatomical variation within a subset of these cortical regions partially mediates the positive association between SES and IQ. Finally, we identify neuroanatomical correlates of SES that exist above and beyond accompanying variation in IQ. Our findings clarify the spatiotemporal patterning of SES-related neuroanatomical variation and inform ongoing efforts to dissect the causal pathways underpinning observed associations between childhood SES and regional brain anatomy.
A theoretical analysis of single molecule protein sequencing via weak binding spectra
Authors: Rodriques Samuel , Marblestone Adam , Boyden Ed 
Published: June 2018

AbstractWe propose and theoretically study an approach to massively parallel single molecule peptide sequencing, based on single molecule measurement of the kinetics of probe binding [1] to the N-termini of immobilized peptides. Unlike previous proposals, this method is robust to both weak and non-specific probe-target affinities, which we demonstrate by applying the method to a range of randomized affinity matrices consisting of relatively low-quality binders. This suggests a novel principle for proteomic measurement whereby highly non-optimized sets of low-affinity binders could be applicable for protein sequencing, thus shifting the burden of amino acid identification from biomolecular design to readout. Measurement of probe occupancy times, or of time-averaged fluorescence, should allow high-accuracy determination of N-terminal amino acid identity for realistic probe sets. The time-averaged fluorescence method scales well to extremely weak-binding probes. We argue that this method could lead to an approach with single amino acid resolution and the ability to distinguish many canonical and modified amino acids, even using highly non-optimized probe sets. This readout method should expand the design space for single molecule peptide sequencing by removing constraints on the properties of the fluorescent binding probes.Author summaryWe simplify the problem of single molecule protein sequencing by proposing and analyzing an approach that makes use of low-affinity, low-specificity binding reagents. This decouples the problem of protein sequencing from the problem of generating a high-quality library of binding reagents against each of the amino acids.
Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model
Authors: Wang Lihui , Sloan Megan A. , Ligoxygakis Petros 
Published: June 2018

ABSTRACTDipteran insects transmit diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knockdown of key components of these pathways in enterocytes (ECs) and intestinal progenitor cells influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of Intestinal Stem Cells (ISCs). Loss of Relish suppressed the latter, resulting in increased parasite numbers and delayed clearance. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism of the dipteran early response to trypanosomatids, crucial for parasite establishment and therefore transmission.AUTHOR SUMMARYNeglected Tropical Diseases are the most common diseases of the world’s poorest people. Many are caused by parasites called trypanosomatids that are transmitted to humans via insects belonging to the order of Diptera (also known as true flies). These flies (including tsetse, sand flies and black flies) are difficult to study in the lab and so the prospect of rapid progress in the basic biology of fly-parasite interaction is bleak. However, a model dipteran species with an extensive “tool-box” is the fruit fly Drosophila melanogaster with its natural trypanosomatid Herpetomonas muscarum. Here we establish the framework of their early interaction with the view that part of this interaction will represent an evolutionary conserved component of the dipteran response to parasite infection and will inform more targeted studies into medically important but difficult to study Diptera.
Precise tuning of gene expression output levels in mammalian cells
Authors: Michaels Yale S. , Barnkob Mike B. , Barbosa Hector , Baeumler Toni A. , Thompson Mary K. , Andre Violaine , Colin-York Huw , Fritzsche Marco , Gileadi Uzi , Sheppard Hilary M. , Knapp David J.H.F. , Milne Thomas A. , Cerundolo Vincenzo , Fulga Tudor A. 
Published: June 2018

ABSTRACTPrecise, analogue regulation of gene expression is critical for development, homeostasis and regeneration in mammals. In contrast, widely employed experimental and therapeutic approaches such as knock-in/out strategies are more suitable for binary control of gene activity, while RNA interference (RNAi) can lead to pervasive off-target effects and unpredictable levels of repression. Here we report on a method for the precise control of gene expression levels in mammalian cells based on engineered, synthetic microRNA response elements (MREs). To develop this system, we established a high-throughput sequencing approach for measuring the efficacy of thousands of miR-17 MRE variants. This allowed us to create a library of microRNA silencing-mediated fine-tuners (miSFITs) of varying strength that can be employed to control the expression of user specified genes. To demonstrate the value of this technology, we used a panel of miSFITs to tune the expression of a peptide antigen in a mouse melanoma model. This analysis revealed that antigen expression level is a key determinant of the anti-tumour immune response in vitro and in vivo. miSFITs are a powerful tool for modulating gene expression output levels with applications in research and cellular engineering.
Real Time Normalization of Fast Photochemical Oxidation of Proteins Experiments by Inline Adenine Radical Dosimetry
Authors: Sharp Joshua S. , Misra Sandeep K. , Persoff Jeffrey J. , Egan Robert W. , Weinberger Scot R. 
Published: June 2018

AbstractHydroxyl radical protein footprinting (HRPF) is a powerful method for measuring protein topography, allowing researchers to monitor events that alter the solvent accessible surface of a protein (e.g. ligand binding, aggregation, conformational changes, etc.) by measuring changes in the apparent rate of reaction of portions of the protein to hydroxyl radicals diffusing in solution. Fast Photochemical Oxidation of Proteins (FPOP) offers an ultra-fast benchtop method for performing HRPF, photolyzing hydrogen peroxide using a UV laser to generate high concentrations of hydroxyl radicals that are consumed on roughly a microsecond timescale. The broad reactivity of hydroxyl radicals means that almost anything added to the solution (e.g. ligands, buffers, excipients, etc.) will scavenge hydroxyl radicals, altering their half-life and changing the effective radical concentration experienced by the protein. Similarly, minute changes in peroxide concentration, laser fluence, and buffer composition can alter the effective radical concentration, making reproduction of data challenging. Here, we present a simple method for radical dosimetry that can be carried out as part of the FPOP workflow, allowing for measurement of effective radical concentration in real time. Additionally, by modulating the amount of radical generated, we demonstrate that FPOP HRPF experiments carried out in buffers with widely differing levels of hydroxyl radical scavenging capacity can be normalized on the fly, yielding statistically indistinguishable results for the same conformer. This method represents a major step in transforming FPOP into a robust and reproducible technology capable of probing protein structure in a wide variety of contexts.
Rod signaling in primate retina: range, routing and kinetics
Authors: Grimes William N , Baudin Jacob , Azevedo Anthony , Rieke Fred 
Published: June 2018

AbstractStimulus or context dependent routing of neural signals through parallel pathways can permit flexible processing of diverse inputs. For example, work in mouse shows that rod photoreceptor signals are routed through several retinal pathways, each specialized for different light levels. This light level-dependent routing of rod signals has been invoked to explain several human perceptual results, but it has not been tested in primate retina. Here we show, surprisingly, that rod signals traverse the primate retina almost exclusively through a single pathway, regardless of light level. Indeed, identical experiments in mouse and primate reveal large differences in how rod signals traverse the retina. These results require reevaluating human perceptual results in terms of flexible computation within this single pathway. This includes a prominent speeding of rod signals with light level – which we show is inherited directly from the rods photoreceptors themselves rather than from different pathways with different kinetics.
The Role of Location-Context Binding in Nonspatial Visual Working Memory
Authors: Cai Ying , Yu Qing , Sheldon Andrew D. , Postle Bradley R. 
Published: June 2018

AbstractSuccessful retrieval of an item from visual working memory (VWM) often requires an associated representation of the trial-unique context in which that item was presented. We dissociated the effects on fMRI signal of memory load versus context binding by comparing nonspatial VWM for one oriented bar vs. three bars individuated by their location on the screen vs. three items drawn from different categories (orientation, color, and luminance), for which location context was superfluous. Delay-period fMRI signal in frontal and parietal cortex was sensitive to stimulus homogeneity rather than to memory load per se. Behavioral performance revealed a broad range in swap errors, an index of the efficacy of context binding, and subjects were classified as high swap error or low swap error. During the delay period, the strength of the representation of stimulus location in parietal cortex predicted individual differences in swap errors. During recall, activity in occipital cortex revealed two dissociable neural correlates of context binding: high swap-error subjects allocated less spatial attention to the location of the probed item and more spatial attention the location of non-probed items; high swap-error subjects also represented the orientation of the probed item more weakly and the orientation of nonprobed items more strongly. Our results suggest context binding is a computation that influences all stages of VWM processing.Significance StatementAlthough we often think of the contents of visual working memory (VWM) as representations of the items that need to be remembered, each item’s trial-unique context is also critical for successful performance. For example, if one observes a red, then a black, then a blue car passing through an intersection, vivid memory for the colors, alone, wouldn’t allow one to execute the instruction “Follow the first of the three cars that just drove by.” Although manipulating load is commonly assumed to isolate storage functions, requiring memory for multiple items drawn from the same category also increases demands on the context binding needed to individuate these items. This experiment tracked the influence of context binding on VWM stimulus processing.
Characterizing Building Blocks of Resource Constrained Biological Networks
Authors: Ren Yuanfang , Ay Ahmet , Dobra Alin , Kahveci Tamer 
Published: June 2018

ABSTRACTIdentification of motifs-recurrent and statistically significant patterns-in biological networks is the key to understand the design principles, and to infer governing mechanisms of biological systems. This, however, is a computationally challenging task. This task is further complicated as biological interactions depend on limited resources, i.e., a reaction takes place if the reactant molecule concentrations are above a certain threshold level. This biochemical property implies that network edges can participate in a limited number of motifs simultaneously. Existing motif counting methods ignore this problem. This simplification often leads to inaccurate motif counts (over-or under-estimates), and thus, wrong biological interpretations. In this paper, we develop a novel motif counting algorithm, Partially Overlapping MOtif Counting (POMOC), that considers capacity levels for all interactions in counting motifs. Our experiments on real and synthetic networks demonstrate that motif count using the POMOC method significantly differs from the existing motif counting approaches, and our method extends to large-scale biological networks in practical time. Our results also show that our method makes it possible to characterize the impact of different stress factors on cell’s organization of network. In this regard, analysis of a S. cerevisiae transcriptional regulatory network using our method shows that oxidative stress is more disruptive to organization and abundance of motifs in this network than mutations of individual genes. Our analysis also suggests that by focusing on the edges that lead to variation in motif counts, our method can be used to find important genes, and to reveal subtle topological and functional differences of the biological networks under different cell states.
BioJupies: Automated Generation of Interactive Notebooks for RNA-seq Data Analysis in the Cloud
Authors: Torre Denis , Lachmann Alexander , Ma’ayan Avi 
Published: June 2018

AbstractInteractive notebooks can make bioinformatics data analyses more transparent, accessible and reusable. However, creating notebooks requires computer programming expertise. Here we introduce BioJupies, a web server that enables automated creation, storage, and deployment of Jupyter Notebooks containing RNA-seq data analyses. Through an intuitive interface, novice users can rapidly generate tailored reports to analyze and visualize their own raw sequencing files, their gene expression tables, or fetch data from >5,500 published studies containing >250,000 preprocessed RNA-seq samples. Generated notebooks have executable code of the entire pipeline, rich narrative text, interactive data visualizations, and differential expression and enrichment analyses. The notebooks are permanently stored in the cloud and made available online through a persistent URL. The notebooks are downloadable, customizable, and can run within a Docker container. By providing an intuitive user interface for notebook generation for RNA-seq data analysis, starting from the raw reads, all the way to a complete interactive and reproducible report, BioJupies is a useful resource for experimental and computational biologists. BioJupies is freely available as a web-based application from:http://biojupies.cloudand as a Chrome extension from theChrome Web Store.
DoubletFinder: Doublet detection in single-cell RNA sequencing data using artificial nearest neighbors
Authors: McGinnis Christopher S. , Murrow Lyndsay M. , Gartner Zev J. 
Published: June 2018

SUMMARYSingle-cell RNA sequencing (scRNA-seq) using droplet microfluidics occasionally produces transcriptome data representing more than one cell. These technical artifacts are caused by cell doublets formed during cell capture and occur at a frequency proportional to the total number of sequenced cells. The presence of doublets can lead to spurious biological conclusions, which justifies the practice of sequencing fewer cells to limit doublet formation rates. Here, we present a computational doublet detection tool – DoubletFinder – that identifies doublets based solely on gene expression features. DoubletFinder infers the putative gene expression profile of real doublets by generating artificial doublets from existing scRNA-seq data. Neighborhood detection in gene expression space then identifies sequenced cells with increased probability of being doublets based on their proximity to artificial doublets. DoubletFinder robustly identifies doublets across scRNA-seq datasets with variable numbers of cells and sequencing depth, and predicts false-negative and false-positive doublets defined using conventional barcoding approaches. We anticipate that DoubletFinder will aid in scRNA-seq data analysis and will increase the throughput and accuracy of scRNA-seq experiments.
Cancer stemness, intratumoral heterogeneity, and immune response across cancers
Authors: Miranda Alex , Hamilton Phineas T , Zhang Allen W , Becht Etienne , Mezheyeuski Artur , Bruun Jarle , Micke Patrick , De Reynies Aurélien , Nelson Brad H 
Published: June 2018

SummaryRegulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype (“sternness”) on the immunological properties of cancer has not been systematically explored. Using gene expression-based metrics, we evaluate the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers. We find pervasive negative associations between cancer stemness and anticancer immunity. This occurs despite high stemness cancers exhibiting increased mutation load, cancer-testis antigen expression, and intratumoral heterogeneity. Stemness was also strongly associated with cell-intrinsic suppression of endogenous retroviral expression and type I interferon signaling and increased expression of several therapeutically accessible signaling pathways. Thus, stemness is not only a fundamental process in cancer progression but may represent a unifying mechanism linking antigenicity, intratumoral heterogeneity, and immune suppression across cancers.
A comparative study and evaluation of ERP reference models in the context of ERP IT-driven implementation
Authors: Al-Sabri Hamdan Mohammed , Al-Mashari Majed , Chikh Azeddine 
Published: June 2018

Purpose
The purpose of this paper is to consider the question of what is an appropriate enterprise resource planning (ERP) reference model for specifying areas of change in the context of IT-driven ERP implementation and through the model matching. There are other implicit goals to increasing the awareness of the reference models, as this highlights the principles embedded in ERP systems and explains the classification of reference models, which is useful in terms of the reuse of knowledge.

Design/methodology/approach
In this paper, a comparison between ERP reference models is conducted using a suitable decision-making technique and the final results are discussed. The comparison depends on nine criteria related to conceptual ERP reference models: scope, abstraction, granularity, views, purpose, simplicity, availability, ease of use for model matching, and target audience.

Findings
This study concludes that the business process reference model is best for specifying areas of change in the context of IT-driven ERP implementations. The final ranking of the alternatives based on all criteria places the system organizational model second, followed by the function and data/object reference models, in that order.

Originality/value
This paper is one of very few studies on the selection of appropriate ERP reference models according to the ERP implementation approach and model matching factors. This research also provides an in-depth analysis of various ERP reference model types.
MARISA “For you, a treat”
Authors: Lopez Carlos Eduardo 
Published: June 2018

Subject area
Entrepreneurs, Strategic planning, Management, Family businesses.

Study level/applicability
Undergraduate and Graduate (as an introductory case study).

Case overview
Marisa® is a consolidated bakery in Guadalajara México, selling a wide variety of dessert products. It has achieved fast growth and has diversified with other brands, either by buying or developing them. Examples are Tía Lola® (economical cakes) and Dolce Natura® (artisanal ice creams). The company founder has maintained not only the growth and development of her brand but also the organizational values and culture. These she has transmitted to her over 400 employees. The company is currently facing expansion.

Expected learning outcomes
The expected learning outcomes are as follows: to distinguish the different expansion strategies; to discuss how to maintain culture and values in a firm despite time and growth; to analyze the current market and long-term objectives, as well as different competitors of the firm; and to make strategic decisions at the corporate level.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 3: Entrepreneurship.