bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Meier-Gorlin Syndrome Mutation in Orc4 Causes Tissue-Specific DNA Replication Defects inDrosophila melanogaster
Authors: McDaniel Stephen L. , Branstad Anna M. , Hollatz Allison J. , Fox Catherine A. , Harrison Melissa M. 
Published: July 2019

AbstractMeier-Gorlin syndrome is a rare recessive disorder characterized by a number of distinct developmental defects, including primordial dwarfism, small ears, and small or missing patella. Genes encoding members of the origin recognition complex (ORC) and additional proteins essential for DNA replication (CDC6, CDT1, GMNN, CDC45, and MCM5) are mutated in individuals diagnosed with MGS. The primary role of ORC is to license origins during the G1 phase of the cell cycle, but it also plays roles in cilia development, heterochromatin formation, and other cellular processes. Because of its essential role in DNA replication, ORC is required for every cell division during development. Thus, it is unclear how the Meier-Gorlin syndrome mutations in ORC lead to the tissue-specific defects associated with the disease. To address this question, we have used Cas9-mediated genome engineering to generate aDrosophila melanogastermodel of individuals carrying a mutation inORC4. Like the people with Meier-Gorlin syndrome, these flies reach adulthood, but have several tissue-specific defects. Genetic analysis revealed that this allele is a hypomorph and that mutant females are sterile. We demonstrated that this sterility is caused by a failure in DNA replication. By leveraging the well-studied Drosophila system, we showed that a disease-causing mutation inorc4disrupts DNA replication, and we propose that in individuals with MGS defects arise preferentially in tissues with a high-replication demand.
Detection of differentially abundant cell subpopulations discriminates biological states in scRNA-seq data
Authors: Zhao Jun , Jaffe Ariel , Li Henry , Lindenbaum Ofir , Sefik Esen , Jackson Ruaidhrí , Cheng Xiuyuan , Flavell Richard , Kluger Yuval 
Published: July 2019

AbstractTraditional cell clustering analysis used to compare the transcriptomic landscapes between two biological states in single cell RNA sequencing (scRNA-seq) is largely inadequate to functionally identify distinct and important differentially abundant (DA) subpopulations between groups. This problem is exacerbated further when using unsupervised clustering approaches where differences are not observed in clear cluster structure and therefore many important differences between two biological states go entirely unseen. Here, we develop DA-seq, a powerful unbiased, multi-scale algorithm that uniquely detects and decodes novel DA subpopulations not restricted to well separated clusters or known cell types. We apply DA-seq to several publicly available scRNA-seq datasets on various biological systems to detect differences between distinct phenotype in COVID-19 cases, melanomas subjected to immune checkpoint therapy, embryonic development and aging brain, as well as simulated data. Importantly, we find that DA-seq not only recovers the DA cell types as discovered in the original studies, but also reveals new DA subpopulations that were not described before. Analysis of these novel subpopulations yields new biological insights that would otherwise be neglected.
A spectacular anomaly in the 4-mer composition of the giant pandoravirus genomes reveals a stringent new evolutionary selection process
Authors: Poirot Olivier , Jeudy Sandra , Abergel Chantal , Claverie Jean-Michel 
Published: July 2019

AbstractThe Pandoraviridae is a rapidly growing family of giant viruses, all of which have been isolated using laboratory strains of Acanthamoeba. The genomes of ten distinct strains have been fully characterized, reaching up to 2.5 Mb in size. These double-stranded DNA genomes encode the largest of all known viral proteomes and are propagated in oblate virions that are among the largest ever-described (1.2 µm long and 0.5 µm wide). The evolutionary origin of these atypical viruses is the object of numerous speculations. Applying the Chaos Game Representation to the pandoravirus genome sequences, we discovered that the tetranucleotide (4-mer) “AGCT” is totally absent from the genomes of 2 strains (P. dulcis and P. quercus) and strongly underrepresented in others. Given the amazingly low probability of such an observation in the corresponding randomized sequences, we investigated its biological significance through a comprehensive study of the 4-mer compositions of all viral genomes. Our results indicate that “AGCT” was specifically eliminated during the evolution of the Pandoraviridae and that none of the previously proposed host-virus antagonistic relationships could explain this phenomenon. Unlike the three other families of giant viruses (Mimiviridae, Pithoviridae, Molliviridae) infecting the same Acanthamoeba host, the pandoraviruses exhibit a puzzling genomic anomaly suggesting a highly specific DNA editing in response to a new kind of strong evolutionary pressure.ImportanceThe recent years have seen the discovery of several families of giant DNA viruses all infecting the ubiquitous amoebozoa of the genus Acanthamoeba. With dsDNA genomes reaching 2.5 Mb in length packaged in oblate particles the size of a bacterium, the pandoraviruses are the most complex and largest viruses known as of today. In addition to their spectacular dimensions, the pandoraviruses encode the largest proportion of proteins without homolog in other organisms, thought to result from a de novo gene creation process. While using comparative genomics to investigate the evolutionary forces responsible for the emergence of such an unusual giant virus family, we discovered a unique bias in the tetranucleotide composition of the pandoravirus genomes that can only result from an undescribed evolutionary process not encountered in any other microorganism.
In situ miRNA delivery from a hydrogel promotes osteogenesis of encapsulated mesenchymal stromal cells
Authors: Carthew James. , Shrestha Surakshya. , Forsythe John. S. , Donderwinkel Ilze. , Truong Vinh. X. , Frith Jessica. E. 
Published: July 2019

AbstractHydrogels have many properties that emulate biological tissues and are therefore attractive candidates for use in tissue engineering. In particular the encapsulation and subsequent differentiation of mesenchymal stem/stromal cells (MSCs) is a strategy that holds great promise for the repair and regeneration of bone and cartilage. However, MSCs are well-known for their sensitivity to mechanical cues, particularly substrate stiffness, and so the inherent softness of hydrogels is poorly matched to the mechanical cues that drive efficient osteogenesis. This limits the success of bone tissue engineering using MSCs encapsulated in a hydrogel. One approach to overcome this limitation is to harness mechanotransductive signalling pathways and override the signals cells receive from their environment. Previous reports have shown that the mechanosensitive miRNAs, miR-100-5p and miR-143-3p can enhance MSC osteogenesis, but this required a complex multi-step procedure to transfect, encapsulate and differentiate the cells. In this study, we develop and characterise a facile system for in situ transfection of MSCs encapsulated within a light-crosslinkable gelatin-PEG hydrogel. Comparing the influence of different transfection agents and hydrogel compositions, we determine the factors affecting transfection agent release and MSC transfection, showing that it is possible to transfect MSCs with miRNAs in situ. We then compare the efficacy of both pretransfection and in situ transfection on the osteogenic capacity of hydrogel-encapsulated MSCs, demonstrating superior mineralisation and osteogenic gene expression for in situ transfected samples. Our platform therefore demonstrates a simple, one-pot system for delivery of pro-osteogenic miRNAs and in situ transfection that is able to enhance MSC osteogenic potential without the need of multi-step transfection procedures, thus demonstrating significant promise for bone tissue engineering.
A neural circuit model for human sensorimotor timing
Authors: Egger Seth W. , Le Nhat M. , Jazayeri Mehrdad 
Published: July 2019

ABSTRACTHumans can rapidly and flexibly coordinate their movements with external stimuli. Theoretical considerations suggest that this flexibility can be understood in terms of how sensory responses reconfigure the neural circuits that control movements. However, because external stimuli can occur at unexpected times, it is unclear how the corresponding sensory inputs can be used to exert flexible control over the ongoing activity of recurrent neural circuits. Here, we tackle this problem in the domain of sensorimotor timing and develop a circuit-level model that provides insight into how the brain coordinates movement times with expected and unexpected temporal events. The model consists of two interacting modules, a motor planning module that controls movement times and a sensory anticipation module that anticipates external events. Both modules harbor a reservoir of latent dynamics and their interaction forms a control system whose output is adjusted adaptively to minimize timing errors. We show that the model’s output matches human behavior in a range of tasks including time interval production, periodic production, synchronization/continuation, and Bayesian time interval reproduction. These results demonstrate how recurrent interactions in a simple and modular neural circuit could create the dynamics needed to control temporal aspects of behavior.
Comparative evaluation of bolus and fractionated administration modalities for two antibody-cytokine fusions in immunocompetent tumor-bearing mice
Authors: Puca Emanuele , De Luca Roberto , Seehusen Frauke , Rodriguez Josep Maria Monné , Neri Dario 
Published: July 2019

AbstractAntibody-cytokine fusion proteins are being considered as biopharmaceuticals for cancer immunotherapy. Tumor-homing cytokine fusions typically display an improved therapeutic activity compared to the corresponding unmodified cytokine products, but toxicity profiles at equivalent doses are similar, since side effects are mainly driven by the cytokine concentration in blood. In order to explore avenues to harness the therapeutic potential of antibody-cytokine fusions while decreasing potential toxicity, we compared bolus and fractionated administration modalities for two tumor-targeting antibody-cytokine fusion proteins based on human interleukin-2 (IL2) and murine tumor necrosis factor (TNF) (i.e., L19-hIL2 and L19-mTNF) in two murine immunocompetent mouse models of cancer (F9 and C51). A comparative quantitative biodistribution analysis with radio-labeled protein preparations revealed that a fractionated administration of L19-hIL2 could deliver comparable product doses to the tumor with decreased product concentration in blood and normal organs, compared to bolus injection. By contrast, L19-mTNF (a product that causes a selective vascular shutdown in the tumor) accumulated most efficiently after bolus injection. Fractionated schedules allowed the safe administration of a cumulative dose of L19-mTNF, which was 2.5-times higher than the lethal dose for bolus injection. Dose fractionation led to a prolonged tumor growth inhibition for F9 teratocarcinomas, but not for C51 colorectal tumors, which responded best to bolus injection. Thus, dose fractionation may have different outcomes for the same antibody-cytokine product in different biological contexts.
Correcting index databases improves metagenomic studies
Authors: Méric Guillaume , Wick Ryan R. , Watts Stephen C. , Holt Kathryn E. , Inouye Michael 
Published: July 2019

AbstractAssessing the taxonomic composition of metagenomic samples is an important first step in understanding the biology and ecology of microbial communities in complex environments. Despite a wealth of algorithms and tools for metagenomic classification, relatively little effort has been put into the critical task of improving the quality of reference indices to which metagenomic reads are assigned. Here, we inferred the taxonomic composition of 404 publicly available metagenomes from human, marine and soil environments, using custom index databases modified according to two factors: the number of reference genomes used to build the databases, and the monophyletic strictness of species definitions. Index databases built following the NCBI taxonomic system were also compared to others using Genome Taxonomy Database (GTDB) taxonomic redefinitions. We observed a considerable increase in the rate of read classification using modified reference index databases as compared to a default NCBI RefSeq database, with up to a 4.4-, 6.4- and 2.2-fold increase in classified reads per sample for human, marine and soil metagenomes, respectively. Importantly, targeted correction for 70 common human pathogens and bacterial genera in the index database increased their specific detection levels in human metagenomes. We also show the choice of index database can influence downstream diversity and distance estimates for microbiome data. Overall, the study shows a large amount of accessible information in metagenomes remains unexploited using current methods, and that the same data analysed using different index databases could potentially lead to different conclusions. These results have implications for the power and design of individual microbiome studies, and for comparison and meta-analysis of microbiome datasets.
Evolution of abbreviated development inHeliocidaris erythrogrammadramatically re-wired the highly conserved sea urchin developmental gene regulatory network to decouple signaling center function from ultimate fate
Authors: Edgar Allison , Byrne Maria , McClay David R. , Wray Gregory A. 
Published: July 2019

AbstractDevelopmental gene regulatory networks (GRNs) describe the interactions among gene products that drive the differential transcriptional and cell regulatory states that pattern the embryo and specify distinct cell fates. GRNs are often deeply conserved, but whether this is the product of constraint inherent to the network structure or stabilizing selection remains unclear. We have constructed the first formal GRN for early development inHeliocidaris erythrogramma, a species with dramatically accelerated, direct development. This life history switch has important ecological consequences, arose rapidly, and has evolved independently many times in echinoderms, suggesting it is a product of selection. We find thatH. erythrogrammaexhibits dramatic differences in GRN topology compared with ancestral, indirect-developing sea urchins. In particular, the GRN sub-circuit that directs the early and autonomous commitment of skeletogenic cell precursors in indirect developers appears to be absent inH. erythrogramma, a particularly striking change in relation to both the prior conservation of this sub-circuit and the key role that these cells play ancestrally in early development as the embryonic signaling center. These results show that even highly conserved molecular mechanisms of early development can be substantially reconfigured in a relatively short evolutionary time span, suggesting that selection rather than constraint is responsible for the striking conservation of the GRN among other sea urchins.
Psychosocial treatment for methamphetamine use and the associated mental health symptoms
Authors: Mann Amrit , Wagstaff Chris 
Published: July 2019

Purpose
Methamphetamine users commonly experience induced methamphetamine associated mental health symptoms. Currently, psychosocial treatment is implemented to reduce use; however, to date, the effectiveness of psychosocial treatment in methamphetamine use and the associated mental health symptoms has not been reviewed. The paper aims to discuss this issue.

Design/methodology/approach
A systematic literature review was performed by searching databases (PubMed, Embase, Ovid MEDLINE, PsychINFO and CINAHL) and following clear inclusion/exclusion criteria.

Findings
In total, 12 studies met the inclusion/exclusion criteria, measuring a variety of psychosocial interventions and measuring a variety of different mental health outcomes. Decreased methamphetamine use was observed in the five studies which recorded this.

Research limitations/implications
Most studies in this review were preliminary trials and only three were RCTs. Additionally, methamphetamine use is a particular problem in Japan and is becoming more prevalent in Europe, yet neither primary nor secondary searching identified papers from these regions.

Practical implications
While the findings may not provide sufficient supporting evidence to instigate changes in clinical practice, this work should be developed further, as it is clear that psychosocial interventions can be successful in treating this population.

Social implications
This review demonstrates that psychosocial treatments can improve symptoms associated with methamphetamine use. Reduction in mental health symptoms has been shown to attract individuals to drug use treatment and thus indirectly reducing methamphetamine use.

Originality/value
Given the consequences of methamphetamine for individuals and communities treatment options must be explored. A review of psychosocial interventions in the treatment of methamphetamine use and associated mental health symptoms had not been done previously. This review provides a foundation for further research.
Store atmosphere and impulse: a cross-cultural study
Authors: Barros Ludmila Bandeira Lima , Petroll Martin de La Martinière , Damacena Cláudio , Knoppe Marc 
Published: July 2019

Purpose
The purpose of this paper is to investigate the influence of store atmosphere on consumers’ positive emotional responses and impulsive purchase behaviour. In addition, it analyses the moderating role of culture characteristics and situational variables on this influence.

Design/methodology/approach
The study carried out a quantitative face-to-face on-site survey of a retail fashion brand in two countries, Brazil and Germany. This paper extended the original model of Jung Chang et al. (2014) based on environment, design and social features (staff) by adding store atmosphere factors such as layout, music and lighting (Mohan et al., 2013), thereby defining store atmosphere as the way customers perceive and experience the combination of all those factors.

Findings
Data analysis from 313 consumers by structural equation modelling (PLS–SEM) showed that most factors influence consumers’ positive emotional responses, but no significant difference between countries. However, the effect of emotions on impulse purchase behaviour is stronger among collectivist consumers (Brazil) than among individualists (Germany).

Originality/value
This study sheds light on the links between store atmosphere and retail market in Brazil and Germany, framing its conclusions in the context of a comparison between cultures. The paper extends the growing research in the area by exploring the moderating role of the individualism–collectivism dimension of national culture in consumer buying behaviour by comparing the strength of various relationships across shoppers from individualistic vs collectivistic cultures.
Paths to perdition: exploring the trajectories of care staff who have abused older people in their care
Authors: Moore Steve 
Published: July 2019

PurposeThe purpose of this paper is to present findings from face-to-face interviews with three former care staff who were proven to have abused some of the older people living in the care and nursing homes in which they had once worked. The research sought to explore the intra-personal dynamics, personal characteristics and work experiences that led these staff to perpetrate abuse.Design/methodology/approachSemi-structured interviews were undertaken with three former care and nursing home staff who had committed abusive acts and the data secured subjected to thematic narrative analysis.FindingsNone of the three people interviewed had intended to become care staff and reported that the interview and induction processes they experienced did little to establish their suitability for the work they would be undertaking or to prepare them for its demands. Participants expressed their generally negative perceptions of older people, particularly those living with dementia, and told of how they also felt that they were under pressure to conform with the often abusive care home regimes that they had entered. They also recounted some specific abusive practices developed to allow them to manage the constant tension between the time available to complete all of the tasks required when “caring” for older people, and revealed their perceptions of external scrutiny of care home conduct and the behaviours developed to deflect the effectiveness of this oversight. Two interview participants also revealed their unfavourable attitudes to some of the people they were employed to care for that were based upon perceptions of ethnic differences, and of how this had contributed to the abuse they perpetrated.Research limitations/implicationsThough the research draws upon the experiences of only three former care staff, the data reveal some of the intra-personal dimensions of individual staff who have engaged in abusive acts, and illuminates how the care home environment with which they interact can engender conditions under which abuse is more likely to occur.Originality/valueUnusually, the paper explores the characteristics, perceptions and experiences of care staff who have actually committed abusive acts against those entrusted to their care.
Big Data in fashion: transforming the retail sector
Authors: Silva Emmanuel Sirimal , Hassani Hossein , Madsen Dag Øivind 
Published: July 2019

Purpose
Big Data is disrupting the fashion retail industry and revolutionising the traditional fashion business models. Nowadays, leading fashion brands and new start-ups are actively engaging with Big Data analytics to enhance their operations and maximise on profitability. In hope of motivating and providing direction to fashion retail managers, industry experts, and academics alike, the purpose of this paper is to consider the most recent and trending applications of Big Data in fashion retailing with the aim of concisely summarising the industry’s current position and status.

Design/methodology/approach
This conceptual paper provides a brief introduction to the emerging topic of Big Data in fashion retailing by briefly synthesising findings from industry, market and academic research.

Findings
Most existing fashion brands are yet to fully engage with Big Data. The authors find that the main reasons underlying the application of Big Data analytics in fashion are trend prediction, waste reduction, consumer experience, consumer engagement and marketing, better quality control, less counterfeits and shortening of supply chains. The authors also identify key challenges which must be overcome for the most fashionable industry to be able to capitalize on Big Data to understand and predict fashion consumer behaviour.

Research limitations/implications
The brief synthesis provides a foundation for future investigations into the use of Big Data in fashion retailing.

Originality/value
This paper serves as an up-to-date introduction to how Big Data can transform fashion retailing and can act as a sound reference guide for fashion industry managers and professionals grappling with Big Data-related issues.