bluuebunny/crossref_metadata_2025_split huggingface dataset:
XopQ induced stromule formation inNicotiana benthamianais causally linked to ETI signaling and depends on ADR1 and NRG1
Authors: Prautsch Jennifer , Erickson Jessica Lee , Özyürek Sedef , Gormanns Rahel , Franke Lars , Parker Jane E. , Stuttmann Johannes , Schattat Martin Hartmut 
Published: December 2021

AbstractInNicotiana benthamiana, expression of theXanthomonaseffector XopQ triggers ROQ1-dependent ETI responses and in parallel accumulation of plastids around the nucleus and the formation of stromules. Both processes were proposed to contribute to ETI-related hypersensitive cell death and thereby to plant immunity. Whether these reactions are directly connected to ETI signaling events has not been tested. Here we utilized transient expression experiments to determine whether XopQ-mediated plastid reactions are a result of XopQ perception by ROQ1 or a consequence of XopQ virulence activity. We find thatN. benthamianamutants lacking ROQ1, both RNLs (NRG1 and ADR1) or EDS1, fail to elicit XopQ-dependent host cell death and stromule formation. Mutants lacking only NRG1 lost XopQ-dependent cell death but retained some stromule induction that was abolished in the RNL double mutant. This analysis aligns XopQ-induced stromules with the ETI signaling cascade but not to host programmed cell death. Furthermore, data reveal that XopQ-triggered plastid clustering is not strictly linked to stromule formation during ETI. Our data suggest that stromule formation, in contrast to chloroplast peri-nuclear dynamics, is an integral part of theN. benthamianaETI response and that both RNL sub-types play a role in this ETI response.One sentence summaryGenetic analysis aligns effector triggered immunity (ETI) induced stromule formation with the ETI signaling cascade but not programmed cell death and questions stromule guided peri-nuclear plastid clustering.
Considering the methodological limitations and external validity issues of pharmacological drug trials in adult ADHD: An umbrella review (Open Protocol)
Authors: Boesen Kim , Paludan-Müller Asger Sand , Ioannidis John PA 
Published: December 2021

AbstractThis is a protocol to an umbrella review entitled, ‘Considering the methodological limitations and external validity issues of pharmacological drug trials in adult ADHD: An umbrella review (Open Protocol)’.
Mortality trends and lengths of stay among hospitalized COVID-19 patients in Ontario and Québec (Canada): a population-based cohort study of the first three epidemic waves
Authors: Xia Yiqing , Ma Huiting , Buckeridge David L , Brisson Marc , Sander Beate , Chan Adrienne , Verma Aman , Ganser Iris , Kronfli Nadine , Mishra Sharmistha , Maheu-Giroux Mathieu 
Published: December 2021

AbstractBackgroundEpidemic waves of COVID-19 strained hospital resources. We describe temporal trends in mortality risk and length of stay in intensive cares units (ICUs) among COVID-19 patients hospitalized through the first three epidemic waves in Canada.MethodsWe used population-based provincial hospitalization data from Ontario and Québec to examine mortality risk and lengths of ICU stay. For each province, adjusted estimates were obtained using marginal standardization of logistic regression models, adjusting for patient-level characteristics and hospital-level determinants.ResultsUsing all hospitalizations from Ontario (N=26,541) and Québec (N=23,857), we found that unadjusted in-hospital mortality risks peaked at 31% in the first wave and was lowest at the end of the third wave at 6-7%. This general trend remained after controlling for confounders. The odds of in-hospital mortality in the highest hospital occupancy quintile was 1.2 (95%CI: 1.0-1.4; Ontario) and 1.6 (95%CI: 1.3-1.9; Québec) times that of the lowest quintile. Variants of concerns were associated with an increased in-hospital mortality. Length of ICU stay decreased over time from a mean of 16 days (SD=18) to 15 days (SD=15) in the third wave but were consistently higher in Ontario than Québec by 3-6 days.ConclusionIn-hospital mortality risks and lengths of ICU stay declined over time in both provinces, despite changing patient demographics, suggesting that new therapeutics and treatment, as well as improved clinical protocols, could have contributed to this reduction. Continuous population-based monitoring of patient outcomes in an evolving epidemic is necessary for health system preparedness and response.
Ribosome changes elicit non-canonical translation for chemosurvival in G0 leukemic cells
Authors: Datta C. , Truesdell SS. , Bukhari SIA. , Ngue H. , Buchanan B. , Wu Keith Q. , Le Tonqueze O. , Lee S. , Granovetter M. , Boukhali M. , Kreuzer J. , Haas W. , Vasudevan S. 
Published: December 2021

AbstractQuiescent leukemic cells survive chemotherapy, with translation changes. Our data reveal that FXR1, a protein amplified in several aggressive cancers, increases in quiescent and chemo- treated leukemic cells, and promotes chemosurvival. This suggests undiscovered roles for this RNA- and ribosome-associated protein in chemosurvival. FXR1 depletion decreases translation and ribosome subunits, with altered rRNAs, snoRNAs, and ribosomal proteins (RPs). We find that FXR1 binds factors that promote ribosome gene transcription and bind snoRNAs. Ribosome changes increased in FXR1-overexpressing cells, including increased snoRNAs and RPLP0/uL10, activate eIF2α kinases. Accordingly, phospho-eIF2α increases, enabling non- canonical translation of survival and immune regulators in FXR1-overexpressing cells. Overriding these with inhibitors reduces chemosurvival. Thus, increased FXR1 in quiescent or chemo-treated leukemic cells, alters ribosomes that trigger stress signals to re-direct translation for chemosurvival.One Sentence SummaryFXR1 alters ribosomes in G0, which induce stress signals to elicit noncanonical translation for AML drug and immune survival.
A reference genome for the critically endangered woylie, Bettongia penicillata ogilbyi
Authors: Peel Emma , Silver Luke , Brandies Parice , Hogg Carolyn J , Belov Katherine 
Published: December 2021

AbstractBiodiversity is declining globally, and Australia has one of the worst extinction records for mammals. The development of sequencing technologies means that genomic approaches are now available as important tools for wildlife conservation and management. Despite this, genome sequences are available for only 5% of threatened Australian species. Here we report the first reference genome for the woylie (Bettongia penicillata ogilbyi), a critically endangered marsupial from Western Australia, and the first genome within the Potoroidae family. The woylie reference genome was generated using Pacific Biosciences HiFi long-reads, resulting in a 3.39 Gbp assembly with a scaffold N50 of 6.49 Mbp and 86.5% complete mammalian BUSCOs. Assembly of a global transcriptome from pouch skin, tongue, heart and blood RNA-seq reads was used to guide annotation with Fgenesh++, resulting in the annotation of 24,655 genes. The woylie reference genome is a valuable resource for conservation, management and investigations into disease-induced decline of this critically endangered marsupial.
Structural basis for topological regulation of Tn3 resolvase
Authors: Montano Sherwin P. , Rowland Sally-J. , Fuller James R. , Burke Mary E. , MacDonald Alasdair I. , Boocock Martin R. , Stark W. Marshall , Rice Phoebe A. 
Published: December 2021

AbstractSite-specific DNA recombinases play a variety of biological roles, often related to the dissemination of antibiotic resistance, and are also useful synthetic biology tools. The simplest sitespecific recombination systems will recombine any two cognate sites regardless of context. Other systems have evolved elaborate mechanisms, often sensing DNA topology, to ensure that only one of multiple possible recombination products is produced. The closely-related resolvases from the Tn3 and γδ transposons have historically served as paradigms for the regulation of recombinase activity by DNA topology. However, despite many proposals, models of the multi-subunit protein-DNA complex (termed the synaptosome) that enforces this regulation have been unsatisfying due to a lack of experimental constraints and incomplete concordance with experimental data. Here we present new structural and biochemical data that lead to a new, detailed model of the Tn3 synaptosome, and discuss how it harnesses DNA topology to regulate the enzymatic activity of the recombinase.
Physiological activation of the nephron central command drives endogenous kidney tissue regeneration
Authors: Gyarmati Georgina , Shroff Urvi Nikhil , Riquier-Brison Anne , Desposito Dorinne , Ju Wenjun , Izuhara Audrey , Deepak Sachin , Burford James L , Kadoya Hiroyuki , Chen Yibu , Rinschen Markus M. , Ahmadi Nariman , Lau Lester , Gill Inderbir S. , Kretzler Matthias , Peti-Peterdi János 
Published: December 2021

AbstractTissue regeneration is limited in several organs including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest existing remodeling capacity. This study uncovered a novel endogenous tissue remodeling mechanism in the kidney that is activated by the loss of body fluid and salt and involves a unique niche of chief cells called macula densa (MD) that control resident progenitor cells via secreted angiogenic, growth and extracellular matrix remodeling factors, cytokines and chemokines. Serial intravital imaging, MD Wnt mouse models and transcriptome analysis provide functional and molecular characterization of this newly identified MD program for kidney regeneration complemented with human and therapeutic translation. The concept that chief cells responding to organ-specific physiological inputs control local progenitors and direct them to remodel or repair tissues may be applicable to other organs and diverse tissue regenerative therapeutic strategies.
Over-expression of wild-typeACVR1in fibrodysplasia ossificans progressiva mice rescues perinatal lethality and inhibits heterotopic ossification
Authors: Yamamoto Masakazu , Stoessel Sean J. , Yamamoto Shoko , Goldhamer David J. 
Published: December 2021

AbstractFibrodysplasia ossificans progressiva (FOP) is a devastating disease of progressive heterotopic bone formation for which effective treatments are currently unavailable. FOP is caused by dominant gain-of-function mutations in the receptor ACVR1 (also known as ALK2), which render the receptor inappropriately responsive to activin ligands. In previous studies, we developed a genetic mouse model of FOP that recapitulates most clinical aspects of the disease. In this model, genetic loss of the wild-typeAcvr1allele profoundly exacerbated heterotopic ossification, suggesting the hypothesis that the stoichiometry of wild-type and mutant receptors dictates disease severity. Here, we tested this model by producing FOP mice that conditionally over-express human wild-type ACVR1. Injury-induced heterotopic ossification (HO) was completely blocked in FOP mice when expression of both the mutant and wild-type receptor were targeted to Tie2-positive cells, which includes fibro/adipogenic progenitors (FAPs). Perinatal lethality ofAcvr1R206H/+mice was rescued by constitutiveACVR1over-expression and these mice survived to adulthood at predicted Mendelian frequencies. Constitutive over-expression ofACVR1also provided protection from spontaneous HO, and the incidence and severity of injury-induced HO in these mice was dramatically reduced. Analysis of pSMAD1/5/8 signaling both in cultured cells andin vivoindicates thatACVR1over-expression functions cell-autonomously by reducing osteogenic signaling in response to activin A. Manipulating the stoichiometry of FOP-causing and wild-type ACVR1 receptors may provide the foundation for novel therapeutic strategies to treat this devastating disease.
Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism, lipid transport and oxidative stress response
Authors: Alpizar-Sosa Edubiel A. , Binti Ithnin Nur Raihana , Wei Wenbin , Pountain Andrew W. , Weidt Stefan K. , Donachie Anne M. , Ritchie Ryan , Dickie Emily A. , Burchmore Richard J. S. , Denny Paul W. , Barrett Michael P. 
Published: December 2021

AbstractAmphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each line, the predominant ergostane-type sterol of wild-type cells was replaced by other sterol species. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of the miltefosine transporter was found. Differences in sensitivity to amphotericin B were apparent, depending on whether cells were grown in HOMEM, supplemented with foetal bovine serum, or a serum free defined medium (DM). These differences appeared to relate to the presence of lipids in the former. Metabolomic analysis after exposure to AmB showed that a large increase in glucose flux via the pentose phosphate pathway preceded cell death in cells sustained in HOMEM but not DM, indicating the oxidative stress was more significantly induced under HOMEM conditions. Several of the lines were tested for ability to infect macrophages and replicate as amastigote forms, alongside their ability to establish infections in mice. While several lines showed reduced virulence, at least one AmB resistant line displayed heightened virulence in mice whilst retaining its resistance phenotype, emphasising the risks of resistance emerging to this critical drug.
Exploring consumer non-knowledge in the agrifood context and its effects on behaviour
Authors: Torres-Ruiz Francisco José , Garrido-Castro Elisa , Gutiérrez-Salcedo María 
Published: December 2021

PurposeConsumer knowledge has been one of the most studied variables in marketing due to its strong influence on consumer behaviour. Knowledge level has traditionally been measured through objective knowledge and the number of correct answers in a battery of items about product characteristics. The authors argue that this analysis could be complemented with other information, that is, the structure of non-knowledge. The main objective of this work is to explore the nature and explanatory potential of this new dimension on consumer behaviour in the agrifood context. The principal hypothesis is that, while they may have similar levels of objective knowledge, there are significant differences between the behaviour of consumers who have a predominant pattern of ignorance (tendency to answer “I don't know”) and those who are in error (tendency to give wrong answers).Design/methodology/approachThe present study draws on data derived from five case studies examining consumer knowledge about agrifood products (olive oils, Iberian ham and orange juice) and certain aspects of consumer behaviour. A sample of 4,112 participants was classified into two non-knowledge profiles: wrong, if most items answered incorrectly in a questionnaire were wrong; or ignorant, if most items answered incorrectly were “don't know”.FindingsThe results obtained supported the argument that complementing the study of consumer knowledge with an analysis of the structure of non-knowledge is worthwhile, as differences within the structure are associated with different patterns of consumer behaviour.Originality/valueIn the present study, it is proposed that the measurement of knowledge be complemented with an analysis of the consumer's non-knowledge structure (items not answered correctly), given its effects on behaviour, an aspect hitherto unconsidered in the literature. To do so, a new index is proposed.
Safety performance prediction and modification strategies for construction projects via machine learning techniques
Authors: Abbasianjahromi Hamidreza , Aghakarimi Mehdi 
Published: December 2021

PurposeUnsafe behavior accounts for a major part of high accident rates in construction projects. The awareness of unsafe circumstances can help modify unsafe behaviors. To improve awareness in project teams, the present study proposes a framework for predicting safety performance before the implementation of projects.Design/methodology/approachThe machine learning approach was adopted in this work. The proposed framework consists of two major phases: (1) data collection and (2) model development. The first phase involved several steps, including the identification of safety performance criteria, using a questionnaire to collect data, and converting the data into useful information. The second phase, on the other hand, included the use of the decision tree algorithm coupled with the k-Nearest Neighbors algorithm as the predictive tool along with the proposing modification strategies.FindingsA total of nine safety performance criteria were identified. The results showed that safety employees, training, rule adherence and management commitment were key criteria for safety performance prediction. It was also found that the decision tree algorithm is capable of predicting safety performance.Originality/valueThe main novelty of the present study is developing an integrated model to propose strategies for the safety enhancement of projects in the case of incorrect predictions.
A local smart city approach in the context of smart environment and urban resilience
Authors: Ateş Mücella , Erinsel Önder Deniz 
Published: December 2021

Purpose
Although smart city studies have increased recently, smart city discussions are made based on general concepts not specific to the region. The region-specific local smart city strategy in the built environment is key to climate resilience in the built environment in the face of natural disasters. The purpose of this paper is to focus on the smart environment, which expresses the spatial dimension of smart cities. This research defines a region-specific smart city model and revealing the role of this model in the resilience against disasters of the built environment.

Design/methodology/approach
The analytical hierarchy process (AHP) method was conducted in four steps. In Step 1, the authors suggested new smart environmental assessment criteria with climatic and geographical data within the scope of the collective mind of the region. In Step 2, they determined the expert group to evaluate within the scope of the AHP method and then compared the significance levels of the current and suggested smart environmental assessment criteria by the AHP method.

Findings
From the results, it turned out that smart urbanization processes, which are trying to relate to local characteristics, are of great importance in terms of ensuring urban resilience. The results also highlight that the existing smart environmental assessment criteria in the literature are insufficient to ensure the climatic resilience of the built environment in the face of natural disasters.

Research limitations/implications
The study is in an intermediary section, which has a gap in the literature due to its subject. Although it has focused on an acute problem and a current research problem, the lack of literature on the field has been a limitation. Determining the cities where the field studies would be conducted has been a major limitation. For an objective hypothesis test within the scope of the AHP method, the sample group should consist of experts working in smart city projects in cities that are in the top 3 in five different smart city rankings, where field studies are conducted. Within this limited cluster, creating a large sample group was an important limitation.

Originality/value
This research looks into the existing gaps of the relation between climate resilience of the built environment and the local smart city approach. This examination will foster a holistic approach in the practice of sustainable smart city in the built environment, thus reinforcing urban resilience and climate studies in the context of smart cities.
Russian merger control: in favor of foreign companies?
Authors: Redkina Anastasiia , Molodchik Mariia , Jardon Carlos 
Published: December 2021

PurposeThe paper aims to reveal the attitude of the Russian competition authorities towards cross-border mergers involving foreign buyers. The study addresses the following question: Is the probability of Russian competition authorities' intervention significantly different when a foreign buyer takes part in the merger? This is the key test to reveal whether competition authorities gravitate towards “economic nationalism” or “promotion of foreign investments”.Design/methodology/approachThe discrete choice model is applied to the dataset of 7,607 merger cases investigated by the Russian competition authorities between 2012 and 2017. The probability of competition authorities' intervention, such as merger correction by using remedies or deal rejection, is used as a measure of special attention.FindingsThe study finds out favoritism patterns of the regulator with regard to foreign companies. In particular, the deals involving a foreign buyer had less chance of intervention, i.e. imposition of remedies, from national competition authorities. The sanctions period does not moderate the probability of approval of a cross-border merger with foreign buyers by the Russian competition authorities.Originality/valueThe paper contributes to merger control literature by addressing the political economy issues. It discovers that, besides regulation by the law, there are hidden motives, such as protectionism or favoritism of foreign companies, which could drive the regulator's decision. Therefore, the studies of cross-border mergers provide an opportunity to investigate the political issues of merger control through the identification of a special attitude to foreign companies and analysis of regularities that might explain such a policy.