bluuebunny/crossref_metadata_2025_split huggingface dataset:
What if we perceive SARS-CoV-2 genomes as documents? Topic modelling using Latent Dirichlet Allocation to identify mutation signatures and classify SARS-CoV-2 genomes
Authors: Nagpal Sunil , Srivastava Divyanshu , Mande Sharmila S. 
Published: August 2020

ABSTRACTTopic modeling is frequently employed for discovering structures (or patterns) in a corpus of documents. Its utility in text-mining and document retrieval tasks in various fields of scientific research is rather well known. An unsupervised machine learning approach, Latent Dirichlet Allocation (LDA) has particularly been utilized for identifying latent (or hidden) topics in document collections and for deciphering the words that define one or more topics using a generative statistical model. Here we describe how SARS-CoV-2 genomic mutation profiles can be structured into a ‘Bag of Words’ to enable identification of signatures (topics) and their probabilistic distribution across various genomes using LDA. Topic models were generated using ~47000 novel corona virus genomes (considered as documents), leading to identification of 16 amino acid mutation signatures and 18 nucleotide mutation signatures (equivalent to topics) in the corpus of chosen genomes through coherence optimization. The document assumption for genomes also helped in identification of contextual nucleotide mutation signatures in the form of conventional N-grams (e.g. bi-grams and tri-grams). We validated the signatures obtained using LDA driven method against the previously reported recurrent mutations and phylogenetic clades for genomes. Additionally, we report the geographical distribution of the identified mutation signatures in SARS-CoV-2 genomes on the global map. Use of the non-phylogenetic albeit classical approaches like topic modeling and other data centric pattern mining algorithms is therefore proposed for supplementing the efforts towards understanding the genomic diversity of the evolving SARS-CoV-2 genomes (and other pathogens/microbes).
When time really is money: in situ quantification of the strobilurin resistance mutation G143A in the wheat pathogen Blumeria graminis f. sp. tritici
Authors: Dodhia Kejal N , Cox Belinda A , Oliver Richard P , Lopez-Ruiz Francisco J 
Published: August 2020

AbstractBackgroundThere has been an inexorable increase in the incidence of fungicide resistance in plant pathogens in recent years. Control of diseases and the management of resistance would be greatly aided by rapid diagnostic methods. Quantitative allele specific PCR (ASqPCR) is an ideal technique for the analysis of fungicide resistance in the field as it can both detect and quantify the frequency of mutations associated with fungicide resistance. We have applied this technique to the fungal pathogenBlumeria graminisf. sp.tritici(Bgt), an obligate biotrophic fungus that causes wheat powdery mildew and is responsible for up to 25% yield loss annually. In Australia, strobilurin resistantBgtwas first discovered in samples from Tasmania and Victoria in 2016. Molecular analysis revealed a nucleotide transversion in the cytochromebc1 enzyme (cytb) complex, resulting in a substitution of alanine for glycine at position 143 (G143A) in Cytb.ResultsWe have developed an in-field ASqPCR assay that can quantify both the resistant (A143) and sensitive (G143)cytballeles down to 1.67% in host andBgtDNA mixtures within 90 min of sample collection. Thein situanalysis of field samples collected during a survey in Tasmania revealed A143 frequencies ranging between 9-100%. We validated the analysis with a newly developed laboratory based digital PCR assay and found no significant differences between the two methods.ConclusionWe have successfully developed an in-field quantification method, for a QoI resistant allele, by pairing an ASqPCR assay on a lightweight qPCR instrument with a quick DNA extraction method. The deployment of this type of methodologies in the field can contribute to the effective in-season management of fungicide resistance.
Oxidative stress induces cell death partially by decreasing both mRNA and protein levels of nicotinamide phosphoribosyltransferase in PC12 cells
Authors: Zhou Cuiyan , Ying Weihai 
Published: August 2020

AbstractNumerous studies have indicated critical roles of NAD+deficiency in both aging and multiple major diseases. It is critical to investigate the mechanisms underlying the NAD+deficiency under the pathological conditions. It has been reported that there was a decreased level of Nicotinamide phosphoribosyltransferase (Nampt) – an important enzyme in the salvage pathway of NAD+synthesis – under certain pathological conditions, while the mechanisms underlying the Nampt decrease require investigation. In this study we used differentiated PC12 cells as a cellular model to investigate the effects of oxidative stress on both the mRNA and protein levels of Nampt, as well as the role of this effect in oxidative stress-induced cell death: First, Nampt plays significant roles in both the NAD+synthesis and survival of the cells under basal conditions; second, H2O2produced significant decreases in both the mRNA levels and the protein levels of Nampt; and third, H2O2induced cell death partially by producing the decreases in the mRNA and protein levels of Nampt, since the Nampt inhibitor or the Nampt activator significantly exacerbated or attenuated the H2O2-induced cell death, respectively. Collectively, our study has indicated that oxidative stress can decrease both the mRNA and protein levels of Nampt, which has indicated a novel mechanism underlying the NAD+deficiency in aging and under multiple pathological conditions. Our study has also indicated that the decreased Nampt levels contribute to the H2O2-induced cell death, suggesting a new mechanism underlying oxidative cell death.
LINE-1 ORF1p RIP-seq reveals widespread association with p-body enriched mRNAs
Authors: Briggs Erica M. , McKerrow Wilson , Mita Paolo , Boeke Jef D. , Logan Susan K. , Fenyö David 
Published: August 2020

AbstractBackgroundLong INterspersed Element-1 (LINE-1) is an autonomous retroelement able to “copy-and-paste” itself into new loci of the host genome through a process called retrotransposition. The LINE-1 bicistronic mRNA codes for two proteins, ORF1p, a nucleic acid chaperone, and ORF2p, a protein with endonuclease and reverse transcriptase activity. Both proteins bind LINE-1 mRNA in cis and are necessary for retrotransposition. While LINE-1 transcription is usually repressed in most healthy somatic cells through a plethora of mechanisms, ORF1p expression has been observed in nearly 50% of tumors, and new LINE-1 insertions have been documented in a similar fraction of tumors, including prostate cancer.ResultsHere, we utilized RNA ImmunoPrecipitation (RIP) and the L1EM analysis software to identify ORF1p bound RNA in prostate cancer cells. We identified LINE-1 loci that were expressed in androgen sensitive and androgen independent cells, that we show are representative of LINE-1 copies expressed in prostate cancer before and after treatment. In all androgen independent cells, we found higher levels of LINE-1 RNA, as well as unique expression patterns of LINE-1 loci. Interestingly, we observed that ORF1p bound many non-LINE-1 mRNA in all prostate cancer cell lines evaluated, and polyA RNA, and RNA localized in p-bodies were especially enriched. Furthermore, the expression levels of many of the identified ORF1p bound mRNAs also correlated with expression of LINE-1 RNA in prostate tumors from The Cancer Genome Atlas (TCGA).ConclusionOur results show a significant remodeling of LINE-1 loci expression in androgen independent cell lines when compared to parental androgen dependent cells, suggesting an evolution of LINE-1 expression during prostate cancer progression. Additionally, our finding that ORF1p bound a significant amount of non-LINE-1 mRNA, and that the enriched ORF1p bound mRNAs are also amplified in LINE-1 expressing TCGA prostate tumors, suggest that ORF1p may play a role in non-LINE-1 RNA processing and regulation of specific transcripts in prostate tumors.
A Survey of the Kinome Pharmacopeia Reveals Multiple Scaffolds and Targets for the Development of Novel Anthelmintics
Authors: Knox Jessica , Zuercher William , Roy Peter J. 
Published: August 2020

AbstractOver one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to anthelmintic drugs used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-specific manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematodeCaenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant inC. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-specific inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.One sentence summaryDruggable Kinases as Anthelmintic Targets
Cytonuclear discordance in the crowned-sparrows,Zonotrichia atricapillaandZonotrichia leucophrys: a mitochondrial selective sweep?
Authors: Taylor Rebecca S. , Bramwell Ashley C. , Clemente-Carvalho Rute , Cairns Nicholas A. , Bonier Frances , Lougheed Stephen C. 
Published: August 2020

ABSTRACTThe golden-crowned (Zonotrichia atricapilla) and white-crowned (Z. leucophrys) sparrows have been presented as a compelling case for rapid speciation. They display divergence in song and plumage with overlap in their breeding ranges implying reproductive isolation, but have almost identical mitochondrial genomes. Previous research proposed hybridization and subsequent mitochondrial introgression as an alternate explanation, but lacked robust nuclear gene trees to distinguish between introgression and incomplete lineage sorting. We test for signatures of these processes betweenZ. atricapillaandZ. leucophrys, and investigate the relationships amongZ. leucophryssubspecies, using mitochondrial sequencing and a reduced representation nuclear genomic dataset. Contrary to the paraphyly evident in mitochondrial gene trees, we confirmed the reciprocal monophyly ofZ. atricapillaandZ. leucophrysusing large panels of single nucleotide polymorphism (SNPs). The pattern of cytonuclear discordance is consistent with limited, historical hybridization and mitochondrial introgression, rather than a recent origin and incomplete lineage sorting between recent sister species. We found evidence of nuclear phylogeographic structure withinZ. leucophryswith two distinct clades. Altogether, our results support the true species status ofZ. atricapillaandZ. leucophrys, and indicate deeper divergences between the two species than inferred using mitochondrial markers. Our results demonstrate the limitations of relying solely on mitochondrial DNA for taxonomy, and raise questions about the possibility of selection on the mitochondrial genome during temperature oscillations (e.g. during the Pleistocene). Historical mitochondrial introgression facilitated by past environmental changes could cause erroneous dating of lineage splitting in other taxa when based on mitochondrial DNA alone.
Laboratory evolution of anticipatory gene regulation inEscherichia coli
Authors: Mahilkar Anjali , Mall Akshat , Saini Supreet 
Published: August 2020

AbstractEnvironmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution ofE. coliin alternating environments of a pentose sugar, rhamnose, and an oxidative stress molecule, paraquat for more than 800 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation, whereby, exposure to rhamnose leads to partial induction of the oxidative stress response regulon. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Overall, we show that in niches where environmental stimuli have a cyclical nature, anticipatory regulation can evolve as an adaptive strategy, in a time course of a few hundred generations. This contributes to our understanding of how environment shapes the topology of regulatory networks in an organism.
An autonomous, but INSIG-modulated, role for the Sterol Sensing Domain in mallostery-regulated ERAD of yeast HMG-CoA reductase
Authors: Wangeline Margaret A , Hampton Randolph Y 
Published: August 2020

AbstractHMG-CoA reductase (HMGR) undergoes feedback regulated degradation as part of sterol pathway control. Degradation of the yeast HMGR isozyme Hmg2 is controlled by the sterol pathway intermediate GGPP, which causes misfolding of Hmg2 to enhance its ERAD by the HRD pathway. GGPP-dependent reversible misfolding of Hmg2 is remarkably similar to classic allosteric control; we recently labeled this process mallostery to fuse the ideas of misfolding and allostery. We have evaluated the role of the Hmg2 sterol sensing domain (SSD) in mallostery, and the involvement of highly conserved INSIG proteins in SSD function. The SSD is a membrane-embedded motif found in many sterol-related proteins. The Hmg2 SSD was critical for in vivo regulated degradation of Hmg2, and required for mallosteric misfolding of GGPP as studied by in vitro limited proteolysis. The Hmg2 SSD functions in mallostery independently of conserved yeast INSIG proteins. However, this autonomous action of the SSD was modulated by INSIG, thus imposing a second layer of control on Hmg2 regulation. SSD-mediated mallostery occurs prior to HRD dependent ubiquitination, defining a pathway regulation involving SSD-mediated misfolding followed by HRD dependent ubiquitination. GGPP dependent misfolding occurred at a much slower rate in the absence of a functional SSD, indicating that the SSD functions to allow physiologically useful rate of GGPP response, and implying that the SSD is not a binding site for GGPP. We used unresponsive Hmg2 SSD mutants to test the importance of quaternary structure in mallosteric regulation: the presence of a non-responsive Hmg2 mutant strongly suppressed regulation of a co-expressed, normal Hmg2. Finally, we have found that GGPP regulated misfolding occurred in detergent solubilized Hmg2, indicating that the mallosteric response is an intrinsic feature of the Hmg2 multimer. The preserved response of Hmg2 when in micellar solution will allow next-level studies on the structural and biophysical features of this novel fusion of regulation and protein quality control.
Phenotypic reconstruction of the last universal common ancestor reveals a complex cell
Authors: Baidouri Fouad El , Venditti Chris , Suzuki Sei , Meade Andrew , Humphries Stuart 
Published: August 2020

AbstractA fundamental concept in evolutionary theory is the last universal common ancestor (LUCA) from which all living organisms originated. While hypotheses regarding the phenotype of LUCA do exist, most are at best based on gene presence or absence. However, despite recent attempts to link genes and phenotypic traits in prokaryotes, it is still inherently difficult to predict phenotype based on the presence or absence of genes alone. Here, we apply a novel approach based on phylogenetically informed ancestral character reconstruction with 22 fundamental descriptors of prokaryotic cells to reconstruct LUCA’s phenotype. We infer that the last universal common ancestor of all living organisms was likely an ovoid cell with a large genome, which probably had a cell wall and was actively motile. Potentially obtaining energy from the oxidation of inorganic compounds, tolerant of saltwater and thriving at temperatures above 70°C, LUCA was probably found living freely in anaerobic conditions in water of neutral pH. Our results depict LUCA as likely to be a far more complex cell than has previously been proposed, challenging the evolutionary model of increased complexity through time in prokaryotes. Given current estimates for the emergence of LUCA we suggest that early life very rapidly evolved considerable cellular complexity.
Is corporate disclosure of environmental performance indicators reliable or biased information? A look at the underlying drivers
Authors: Tadros Hani , Magnan Michel , Boulianne Emilio 
Published: August 2020

Purpose
This study aims to examine the disclosure determinants of environmental performance indicators (EPIs) for a sample of US firms to understand if these disclosures are reliable or whether they are biased towards the reporting of positive information.

Design/methodology/approach
The study uses a panel data analysis to examine the association between firms’ EPIs disclosures and their environmental performances, and other economic and legitimacy factors.

Findings
The results show that firms’ disclosures are not associated with the level of environmental performance and that firms continue to provide EPI information even if they witness a decline in their environmental performance. The evidence suggests that firms’ environmental disclosures are reliable and indicative of their environmental performance.

Practical implications
The findings suggest that mandating EPI disclosures may increase the level of the information reported and reduce firms’ discretion over the disclosure of such information.

Originality/value
Reporting of EPIs is directly linked to firms’ environmental performances. By examining the association between EPI disclosures and environmental performance, the study contributes to the ongoing debate about firms’ reporting and whether it is informative to its stakeholders or whether firms use this type of information to legitimize their operations and portray it in a positive light.
Outcome and impact indicators for nanotechnology policies
Authors: Soltani Ali Mohammad , Tabatabaeian Seyed Habibollah , Hanafizadeh Payam , Bamdadsoofi Jahanyar 
Published: August 2020

Purpose
The purpose of this paper is to suggest indicators for evaluating Iran national nanotechnology plan at the policy and program levels. Governments are required to evaluate their policies to be accountable to their audience and to improve their policies. The evaluation of nanotechnology policies both in academic and governmental institutions has been mainly confined to measuring the research and development outputs, while explicit models are required for evaluating national nanotechnology policies and programs. In other words, although policies are translated into several activities, it does not mean that the evaluation of activities results in holistic policy evaluation.

Design/methodology/approach
The present research uses a qualitative method to explore the process of developing a model for assessing nanotechnology policymaking in Iran. Expert opinions have been collected and analyzed by using local and international surveys to validate different elements of the model.

Findings
The model includes the evaluation time-frame, criteria and indicators for policy and program levels. Assessment at program and policy levels, as distinct from activity evaluation, measures the ultimate objectives of a policy intervention, based on which the outcome and impact indicators should be developed. This paper argues that the Iran national nanotechnology policy should be evaluated and revised triennially based on the model in which 46 outcome and impact indicators are included under three general criteria of appropriateness, efficiency and effectiveness. A number of these indicators should be evaluated annually or biannually.

Originality/value
The evaluation of nanotechnology plans has been mainly limited to assessing the research and development outputs that are related to the activity level. The main value of this work is developing outcome and impact indicators that are related to policy and program levels.
A systematic review on high performance organization
Authors: Do Thanh Tung , Mai Ngoc Khuong 
Published: August 2020

PurposeThis paper aims to synthesize existing knowledge on high performance organization (HPO) in terms of definitions, contemporary trends and findings from empirical studies; from which areas for future research can be proposed.Design/methodology/approachThis systematic literature review applies the matrix method to analyze major HPO literature in peer-reviewed English articles. A total of 73 articles have been found in 59 journals.FindingsThere are three key findings that emerged from this study. First, the research on HPO has been burgeoned in the past decades, generating several compelling studies in different contexts. The trend of HPO research is now shifting from theory development to theory validation. Second, HPO has been defined in various ways in the extant literature. However, they all address the importance of aligning the firms’ resources with the market demand and integrating various types of performance to measure HPO relative to competitors for a prolonged period. Third, an assessment of empirical HPO studies revealed gaps in terms of the research context, research design and the HPO’s nomological network.Research limitations/implicationsThe literature search in this review targeted at only articles published in the English language; therefore, publications in other languages were not included.Originality/valueThe strength of this study is that it provided an updated systematic review of HPO literature, is therefore, valuable in providing an overall picture of the current state of HPO research and providing potential directions for future studies.