bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic diversity of theLILRB1andLILRB2coding regions in an admixed Brazilian population sample
Authors: Guimarães de Oliveira Maria Luiza , Castelli Erick C. , Veiga-Castelli Luciana C. , Pereira Alison E. , Marcorin Letícia , Carratto Thássia M. T. , Souza Andreia S. , Andrade Heloisa S. , Simões Aguinaldo L. , Donadi Eduardo A. , Courtin David , Sabbagh Audrey , Giuliatti Silvana , Mendes-Junior Celso Teixeira 
Published: April 2021

ABSTRACTLeukocyte Immunoglobulin (Ig)-like Receptors (LILR) LILRB1 and LILRB2 play a pivotal role in maintaining self-tolerance and modulating the immune response through interaction with classical and non-classical Human Leukocyte Antigen (HLA) molecules. Although both diversity and natural selection patterns over HLA genes have been extensively evaluated, little information is available concerning the genetic diversity and selection signatures on theLIRB1/2regions. Therefore, we identified theLILRB1/2genetic diversity using next-generation sequencing in a population sample comprising 528 healthy control individuals from São Paulo State, Brazil. We identified 58LILRB1Single Nucleotide Variants (SNVs), which gave rise to 13 haplotypes with at least 1% of frequency. ForLILRB2, we identified 41 SNVs arranged into 11 haplotypes with frequencies above 1%. We found evidence of either positive or purifying selection onLILRB1/2coding regions. Some residues in both proteins showed to be under the effect of positive selection, suggesting that amino acid replacements in these proteins resulted in beneficial functional changes. Finally, we have shown that allelic variation (six and five amino acid exchanges in LILRB1 and LILRB2, respectively) affects the structure and/or stability of both molecules. Nonetheless, LILRB2 has shown higher average stability, with no D1/D2 residue affecting protein structure. Taken together, our findings demonstrate thatLILRB1andLILRB2are highly polymorphic and provide strong evidence supporting the directional selection regime hypothesis.
Sensitive high-throughput assays for tumour burden reveal the response of aDrosophila melanogastermodel of colorectal cancer to standard chemotherapies
Authors: Adams Jamie , Casali Andreu , Campbell Kyra 
Published: April 2021

AbstractDrosophila melanogaster (Drosophila)models of cancer are emerging as powerful tools to investigate the basic mechanisms underlying tumour progression and identify novel therapeutics. Rapid and inexpensive, it is possible to carry out genetic and drug screens at a far larger scale than in vertebrate organisms. Such whole-organism-based drug screens permits assessment of drug absorption and toxicity, reducing the possibility of false positives. Activating mutations in the Wnt and Ras signalling pathways are common in many epithelial cancers, and when driven in the adultDrosophilamidgut, it induces aggressive intestinal tumour-like outgrowths that recapitulate many aspects of human colorectal cancer (CRC). Here we have taken aDrosophilaCRC model in which tumourous cells are marked with both GFP and luciferase reporter genes, and developed novel high-throughput assays for quantifying tumour burden. Leveraging these assays, we find that theDrosophilaCRC model responds rapidly to treatment with standard CRC-drugs, opening the door to future rapid genetic and drug screens.
An inter-channel cooperative mechanism mediates PIEZO1’s exquisite mechanosensitivity
Authors: Wijerathne Tharaka , Ozkan Alper D. , Jiang Wenjuan , Luo Yun , Lacroix Jérôme J. 
Published: April 2021

ABSTRACTThe bowl-shaped structure of PIEZO channels is predicted to flatten in response to mechanical stimuli, gating their pore open. However, how this unique structure allows them to detect exquisitely small changes in membrane tension remains unclear. Here, using pressure clamp electrophysiology, modeling, and molecular dynamics simulations, we show that the single channel open probability of PIEZO1 increases weakly with respect to pressure-induced tension. In contrast, when multiple channels are present in a membrane patch, channel open probability increases steeply as a function of the number of open channels. These cooperative effects are consistent with an inter-channel energetic repulsion due to the local membrane deformation created by the non-planar PIEZO structure. When channels open, this deformation shrinks, allowing open channels to diffuse closer to each other, thus delaying closure. This study reveals how PIEZO1 channels acquire their exceptional mechanosensitivity and suggests a possible mechanism by which cells could rapidly tune mechanosensitivity.
Predicting the Genomic Resolution of Bulk Segregant Analysis
Authors: Shen Runxi , Messer Philipp W. 
Published: April 2021

AbstractBulk segregant analysis (BSA) is a technique for identifying the genetic loci that underlie phenotypic trait differences. The basic approach of this method is to compare two pools of individuals from the opposing tails of the phenotypic distribution, sampled from an interbred population. Each pool is sequenced and scanned for alleles that show divergent frequencies between the pools, indicating potential association with the observed trait differences. BSA has already been successfully applied to the mapping of various quantitative trait loci in organisms ranging from yeast to maize. However, these studies have typically suffered from rather low mapping resolution, and we still lack a detailed understanding of how this resolution is affected by experimental parameters. Here, we use coalescence theory to calculate the expected genomic resolution of BSA. We first show that in an idealized interbreeding population of infinite size, the expected length of the mapped region is inversely proportional to the recombination rate, the number of generations of interbreeding, and the number of genomes sampled, as intuitively expected. In a finite population, coalescence events in the genealogy of the sample reduce the number of potentially informative recombination events during interbreeding, thereby increasing the length of the mapped region. This is incorporated into our theory by an effective population size parameter that specifies the pairwise coalescence rate of the interbreeding population. The mapping resolution predicted by our theory closely matches numerical simulations. Furthermore, we show that the approach can easily be extended to modifications of the crossing scheme. Our framework enables researchers to predict the expected power of their mapping experiments, and to evaluate how their experimental design could be tuned to optimize mapping resolution.
Molecular approaches reveal speciation between red and blue flowered plants in the MediterraneanLysimachia arvensisandLysimachia monelli(Primulaceae)
Authors: Jiménez-López F.J. , Viruel J. , Arista M. , Ortiz P.L. , Talavera M. 
Published: April 2021

AbstractFlower colour constitutes a pivotal evolutionary force in speciation. The MediterraneanLysimachia arvensisandL. monelliare morphologically variable species having both blue or red flowered plants. Previous studies suggested thatL. arvensisplants differing in colour are diverging lineages, but this variation has not been considered in a phylogenetic context. We reconstruct the phylogenetic signal and the ancestral states of flower colour of MediterraneanLysimachiaspecies by using nuclear (ITS) and three plastid markers. Blue and red specimens are nested in two independent clades in the ITS tree, thus supporting thatL. arvensisandL. monelliare polyphyletic, whereas low phylogenetic resolution was found in plastid markers. Blue-floweredL. arvensisis reconstructed sister toL. talaveraein a monophyletic clade sister to the remainingLysimachia. Red-floweredL. arvensisis reconstructed sister to red-floweredL. monelliin a monophyletic clade sister to blue-floweredL. monelliandL. foemina. Our results suggest that colour lineages inL. arvensisandL. monelliconstitute different species, but flower colour did not promote the separation of these lineages. We propose a new name for blue-floweredL. arvensis(L. loeflingii) and a new combination for red-floweredL. monelli(L. collina).
Unraveling the influences of sequence and position on yeast uORF activity using massively parallel reporter systems and machine learning
Authors: May Gemma , Akirtava Christina , Agar-Johnson Matthew , Micic Jelena , Woolford John , McManus Joel 
Published: April 2021

AbstractUpstream open reading frames (uORFs) are potentcis-acting regulators of mRNA translation and nonsense-mediated decay (NMD). While both AUG- and non-AUG initiated uORFs are ubiquitous in ribosome profiling studies, few uORFs have been experimentally tested. Consequently, the relative influences of sequence, structural, and positional features on uORF activity have not been determined. We quantified thousands of yeast uORFs using massively parallel reporter assays in wildtype and Δupf1yeast. While nearly all AUG uORFs were robust repressors, most non-AUG uORFs had relatively weak impacts on expression. Machine learning regression modeling revealed that uORF functions are strongly impacted by both their sequences and locations within transcript leaders. Indeed, alternative transcription start sites highly influenced uORF activity. These results define the scope of natural uORF activity, identify features associated with translational repression and NMD, and suggest that the locations of uORFs in transcript leaders are nearly as important as uORF sequences.
Personality-specific pathways from peer victimization to adolescent alcohol misuse: A multilevel longitudinal moderated mediation analysis
Authors: Laroque Flavie M. , Boers Elroy , Afzali Mohammad H. , Conrod Patricia J. 
Published: April 2021

AbstractPeer victimization is common in adolescence and have been associated with a broad variety of psychopathology and alcohol use. The present study assessed whether peer victimization has a time-varying effect on alcohol use through internalizing and externalizing symptoms and whether this indirect association throughout time is moderated by personality. This 5-year longitudinal study (3,800 grade 7 adolescents) used Bayesian multilevel moderated mediation models: independent variable was peer victimization; moderators were four personality dimensions (anxiety sensitivity, hopelessness, impulsivity, and sensation seeking); internalizing symptoms (anxiety, depressive symptoms) and externalizing symptoms (conduct, hyperactivity problems) were the mediators; and alcohol use, the outcome. Results indicated significant between, within, and lagged effects on alcohol use through internalizing and externalizing symptoms. There was significant between and within effects on alcohol use through internalizing symptoms for adolescents with high anxiety sensitivity and hopelessness, and significant between, within, and lagged effects on alcohol use through externalizing for adolescents with high impulsivity and sensation seeking. These findings implicate two risk pathways that account for how peer victimization enhances alcohol use risk and emphasize the importance of personality profiles that can shape the immediate and long-term consequences of victimization.
Cellulomonas zeaesp. nov.,Lelliottia zeaesp. nov.,Paraburkholderia zeaesp. nov. andSphingomonas zeigerminissp. nov., four new bacterial species isolated fromZea maysand other hosts
Authors: Seaton Sarah , Lemaire Jacqueline , Inderbitzin Patrik , Knight-Connoni Victoria , Trujillo Martha E. 
Published: April 2021

ABSTRACTFour novel bacterial species collected from healthy tissues of corn, rice and soybean plants in the United States are described. These includeCellulomonas zeaesp. nov. isolated from corn in Indiana;Lelliottia zeaesp. nov. from corn in Indiana and rice in Arkansas;Paraburkholderia zeaesp. nov. isolated from corn in Iowa; andSphingomonas zeigerminissp. nov. from corn in Mississippi and soy in Arkansas. No pathogenic strains are known for any of the novel species based on genome comparisons to assemblies in GenBank.
Topoisomerase I Essentiality, DnaA-independent Chromosomal Replication, and Transcription-Replication Conflict inEscherichia coli
Authors: Leela J Krishna , Raghunathan Nalini , Gowrishankar J 
Published: April 2021

AbstractTopoisomerase I (Topo I) ofEscherichia coli, encoded bytopA, acts to relax negative supercoils in DNA. Topo I deficiency results in hypernegative supercoiling, formation of transcription-associated RNA-DNA hybrids (R-loops), and DnaA- andoriC-independent constitutive stable DNA replication (cSDR), but some uncertainty persists as to whethertopAis essential for viability inE. coliand related enterobacteria. Here we show that severaltopAalleles, including ΔtopA, confer lethality in derivatives of wild-typeE. colistrain MG1655. Viability in absence of Topo I was restored with two perturbations, neither of which reversed the hypernegative supercoiling phenotype: (i) in a reduced-genome strain MDS42, or (ii) by an RNA polymerase (RNAP) mutationrpoB*35that has been reported to alleviate the deleterious consequences of RNAP backtracking and transcription-replication conflicts. Four phenotypes related to cSDR were identified fortopAmutants: (i) One of thetopAalleles rescued ΔdnaAlethality; (ii) indnaA+derivatives, Topo I deficiency generated a characteristic copy number peak in the terminus region of the chromosome; (iii)topAwas synthetically lethal withrnhA(encoding RNase HI, whose deficiency also confers cSDR); and (iv)topA rnhAsynthetic lethality was itself rescued by ΔdnaA. We propose that the terminal lethal consequence of hypernegative DNA supercoiling inE. coli topAmutants is RNAP backtracking during transcription elongation and associated R-loop formation, which in turn lead to transcription-replication conflicts and to cSDR.ImportanceIn all life forms, double helical DNA exists in a topologically supercoiled state. The enzymes DNA gyrase and topoisomerase I act, respectively, to introduce and to relax negative DNA supercoils inEscherichia coli. That gyrase deficiency leads to bacterial death is well established, but the essentiality of topoisomerase I for viability has been less certain. This study confirms that topoisomerase I is essential forE. coliviability, and suggests that in its absence aberrant chromosomal DNA replication and excessive transcription-replication conflicts occur that are responsible for lethality.
An infectious Rous Sarcoma Virus Gag mutant that is defective in nuclear cycling
Authors: Ricaña Clifton L , Johnson Marc C 
Published: April 2021

AbstractDuring retroviral replication, unspliced viral genomic RNA (gRNA) must escape the nucleus for translation into viral proteins and packaging into virions. “Complex” retroviruses such as Human Immunodeficiency Virus (HIV) use cis-acting elements on the unspliced gRNA in conjunction with trans-acting viral proteins to facilitate this escape. “Simple” retroviruses such as Mason-Pfizer Monkey Virus (MPMV) and Murine Leukemia Virus (MLV) exclusively use cis-acting elements on the gRNA in conjunction with host nuclear export proteins for nuclear escape. Uniquely, the simple retrovirus Rous Sarcoma Virus (RSV) has a Gag structural protein that cycles through the nucleus prior to plasma membrane binding. This trafficking has been implicated in facilitating gRNA nuclear export and is thought to be a required mechanism. Previously described mutants that abolish nuclear cycling displayed enhanced plasma membrane binding, enhanced virion release, and a significant loss in genome incorporation resulting in loss of infectivity. Here, we describe a nuclear cycling deficient RSV Gag mutant that has similar plasma membrane binding and genome incorporation to WT virus and surprisingly, is replication competent albeit with a slower rate of spread compared to WT. This mutant suggests that RSV Gag nuclear cycling is not strictly required for RSV replication.ImportanceWhile mechanisms for retroviral Gag assembly at the plasma membrane are beginning to be characterized, characterization of intermediate trafficking locales remain elusive. This is in part due to the difficulty of tracking individual proteins from translation to plasma membrane binding. RSV Gag nuclear cycling is a unique phenotype that may provide comparative insight to viral trafficking evolution and may present a model intermediate to cis- and trans-acting mechanisms for gRNA export.
Mucin-mimetic glycan arrays integrating machine learning for analyzing receptor pattern recognition by influenza A viruses
Authors: Lucas Taryn M. , Gupta Chitrak , Altman Meghan O. , Sanchez Emi , Naticchia Matthew R. , Gagneux Pascal , Singharoy Abhishek , Godula Kamil 
Published: April 2021

ABSTRACTInfluenza A viruses (IAVs) exploit host glycans in airway epithelial mucosa to gain entry and initiate infection. Rapid detection of changes in IAV specificity towards host glycan classes can provide early indication of virus transmissibility and infection potential. IAVs use hemagglutinins (HA) to bind sialic acids linked to larger glycan structures and a switch in HA specificity from α2,3-to α2,6-linked sialoglycans is considered a prerequisite for viral transmission from birds to humans. While the changes in HA structure associated with the evolution of binding phenotype have been mapped, the influence of glycan receptor presentation on IAV specificity remains obscured. Here, we describe a glycan array platform which uses synthetic mimetics of mucin glycoproteins to model how receptor presentation in the mucinous glycocalyx, including glycan type and valency of the glycoconjugates and their surface density, impact IAV binding. We found that H1N1 virus produced in embryonated chicken eggs, which recognizes both receptor types, exclusively engaged mucin-mimetics carrying α2,3-linked sialic acids in their soluble form. The virus was able utilize both receptor structures when the probes were immobilized on the array; however, increasing density in the mucin-mimetic brush diminished viral adhesion. Propagation in mammalian cells produced a change in receptor pattern recognition by the virus, without altering its HA affinity, toward improved binding of α2,6-sialylated mucin mimetics and reduced sensitivity to surface crowding of the probes. Application of a support vector machine (SVM) learning algorithm as part of the glycan array binding analysis efficiently characterized this shift in binding preference and may prove useful to study the evolution of viral responses to a new host.
Death in the Spanish fire services: a curriculum development study
Authors: Leiva Santos Juan Pablo , García-Llana Helena , Pablo Victor , Liébana Maya , Kellehear Allan 
Published: April 2021

Purpose
The purpose of this paper is to understand the need and resources firefighters have to deal with death and dying (D&D) that they encounter whilst on duty and to present a curriculum to support D&D issues for firefighters.

Design/methodology/approach
A qualitative methodology involving focus groups was conducted in two fire stations in Spain. The sample was 38 male participants with a mean age of 46 y/o (range: 30-59 years) and an average tenure of employment of 18 years (range: 6-35 years). Data were subjected to a thematic analysis. Dual coding of the transcripts in addition to member checking enhanced analysis.

Findings
Nine themes emerged: witnessing D&D during rescue operations; memories about D&D and trauma; impact on firefighter’s families; decision-making process under stress; teamwork: protective and self-support; inadequate D&D preparation and training; adequate technical and physical training preparation; relationship between equipment, legal-moral obligation, and victims’ outcomes; communication issues: toward the victim and/or their relatives. These themes were subsequently framed into three basic domains: personal impact of D&D, team impact of D&D, and victim impact. Each domain, in its turn, is covered by three curriculum topics. The curriculum’s pedagogy is primarily based on experimental-reflective activities during 16 study-hours.

Research limitations/implications
The absence of female participants. All fire stations were in cities with no more than 150,000 inhabitants.

Practical implications
Individuals who take this curriculum will: increase their ability for self-care and resilience; improve teamwork, leadership skills, and to decrease burnout; provide more effective care for victims; provide skills to cope with compassion fatigue; reduced the levels of post-traumatic stress disorders.

Originality/value
Understanding firefighters’ needs with relation to D&D, and assessing the resources available to mitigate these issues will provide a comprehensive approach to their education and promote health both personally and professionally. A comparable curriculum or proposal has not been previously identified.
On the regulatory changes in government accounting development in Indonesia
Authors: Boolaky Pran Krishansing , Mirosea Nitri , Singh Kishore 
Published: April 2021

Purpose
The purpose of this paper is to inquire into the history of government accounting, using a well-grounded periodisation, in order to provide a chronology of government accounting development (GAD) in Indonesia from 1845 to 2015 focusing on development on accounting regulations and systems and practices in local government in Indonesia.

Design/methodology/approach
It collects archival data and then uses a descriptive tradition of research to capture mainly regulatory changes affecting GAD from colonial to post-colonial period.

Findings
The paper reports major regulatory changes, evolution in local government accounting practice, development of government accounting standards (GASt) and converging GASs with international standards.

Research limitations/implications
This study is important to accounting historians and other academics because it provides a detailed chronicle of accounting regulatory changes in Indonesia which can be used for future research. The limitation(s) of this study is that is data collection which was not easily accessible and as results have to rely on various sources.

Practical implications
The study has an important practical implication. It has produced a time series register of regulatory changes affecting GAD in Indonesia. It can be used as a reference document in the National Library of Indonesia and also by academics for future research.

Originality/value
A times series register, for the first time, is produced which provides a comprehensive chronology of accounting development in Indonesia.
Learning from unlabelled real seismic data: Fault detection based on transfer learning
Authors: Zhou Ruoshui , Yao Xingmiao , Hu Guangmin , Yu Fucai 
Published: April 2021

ABSTRACTSignificant advances have been made towards fault detection using deep learning. However, the fault labelling of seismic data requires great human effort. The resulting small sample problem makes traditional deep learning methods difficult to achieve desired results. Existing research proposes to train a deep learning model with labelled synthetic seismic data to get good fault detection results. However, due to the complexity of the actual geological situation, there are inevitable differences between synthetic seismic data and real seismic data in many aspects such as seismic signal frequency, frequency of fault distribution and degree of noise disturbance, which lead to the fact that the deep learning model trained by synthetic seismic data is difficult to get good fault detection result in field data applications. We propose to use transfer learning to reduce the impact of data differences to solve this problem: part of the deep transfer learning model is used to learn fault‐related features. And the other part of the deep transfer learning model is used to mine common features between the real seismic data and the synthetic seismic data, which makes the deep transfer learning model more suitable for real seismic data. Compared with the latest research progress, our method can greatly improve the effect of fault detection without real data label, which can significantly save the cost of manual label processing.