bluuebunny/crossref_metadata_2025_split huggingface dataset:
High sensitivity dia-PASEF proteomics with DIA-NN and FragPipe
Authors: Demichev Vadim , Yu Fengchao , Teo Guo Ci , Szyrwiel Lukasz , Rosenberger George A. , Decker Jens , Kaspar-Schoenefeld Stephanie , Lilley Kathryn S. , Mülleder Michael , Nesvizhskii Alexey I. , Ralser Markus 
Published: March 2021

AbstractThe dia-PASEF technology exploits ion mobility separation for high-sensitivity analysis of complex proteomes. Here, we demonstrate neural network-based processing of the ion mobility data, which we implement in the DIA-NN software suite. Using spectral libraries generated with the MSFragger-based FragPipe computational platform, the DIA-NN analysis of dia-PASEF raw data increases the proteomic depth by up to 69% compared to the originally published dia-PASEF workflow. For example, we quantify over 5200 proteins from 10ng of HeLa peptides separated with a 95-minute nanoflow gradient, and over 5000 proteins from 200ng using a 4.8-minute separation with an Evosep One system. In complex samples, featuring a mix of human and yeast lysates, the workflow detects over 11700 proteins in single runs acquired with a 100-minute nanoflow gradient, while demonstrating quantitative precision. Hence, the combination of FragPipe and DIA-NN provides a simple-to-use software platform for dia-PASEF data analysis, yielding significant gains in high-sensitivity proteomics.
Aerodynamics and motor control of ultrasonic vocalizations for social communication in mice and rats
Authors: Håkansson Jonas , Jiang Weili , Xue Qian , Zheng Xudong , Ding Ming , Agarwal Anurag A. , Elemans Coen P.H. 
Published: March 2021

AbstractRodent ultrasonic vocalizations (USVs) are crucial to their social communication and a widely used translational tool for linking gene mutations to behavior. To maximize the causal interpretation of experimental treatments, we need to understand how neural control affects USV production. However, both the aerodynamics of USV production and its neural control remain poorly understood. Here we test three intralaryngeal whistle mechanisms - the wall and alar edge impingement, and shallow cavity tone - by combining in vitro larynx physiology and individual-based 3D airway reconstructions with fluid dynamics simulations. Our results show that in the mouse and rat larynx USVs are produced by a glottal jet impinging on the thyroid inner wall. Furthermore, we implemented an empirically based motor control model that predicts motor gesture trajectories of USV call types. Our work provides a quantitative neuromechanical framework to evaluate the contributions of brain and body in shaping USVs, and a first step in linking descending motor control to USV production.
Transgenic mice forin vivoepigenome editing with CRISPR-based systems
Authors: Gemberling Matthew , Siklenka Keith , Rodriguez Erica , Tonn-Eisinger Katherine R. , Barrera Alejandro , Liu Fang , Kantor Ariel , Li Liqing , Cigliola Valentina , Hazlett Mariah F. , Williams Courtney , Bartelt Luke C. , Madigan Victoria J. , Bodle Josephine , Daniels Heather , Rouse Douglas C. , Hilton Isaac B. , Asokan Aravind , Ciofani Maria , Poss Kenneth D. , Reddy Timothy E. , West Anne E. , Gersbach Charles A. 
Published: March 2021

AbstractThe discovery, characterization, and adaptation of the RNA-guided clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 system has greatly increased the ease with which genome and epigenome editing can be performed. Fusion of chromatin-modifying domains to the nuclease-deactivated form of Cas9 (dCas9) has enabled targeted gene activation or repression in both cultured cells andin vivoin animal models. However, delivery of the large dCas9 fusion proteins to target cell types and tissues is an obstacle to widespread adoption of these tools forin vivostudies. Here we describe the generation and validation of two conditional transgenic mouse lines for targeted gene regulation, Rosa26:LSL-dCas9-p300 for gene activation and Rosa26:LSL-dCas9-KRAB for gene repression. Using the dCas9p300and dCas9KRABtransgenic mice we demonstrate activation or repression of genes in both the brain and liverin vivo, and T cells and fibroblastsex vivo. We show gene regulation and targeted epigenetic modification with gRNAs targeting either transcriptional start sites (TSS) or distal enhancer elements, as well as corresponding changes to downstream phenotypes. These mouse lines are convenient and valuable tools for facile, temporally controlled, and tissue-restricted epigenome editing and manipulation of gene expressionin vivo.
Comparative host interactomes of the SARS-CoV-2 nonstructural protein 3 and human coronavirus homologs
Authors: Almasy Katherine M. , Davies Jonathan P. , Plate Lars 
Published: March 2021

ABSTRACTHuman coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 proteins interact with the host cell, non-structural protein 3 (nsp3) has largely been omitted from the analyses. Nsp3 is a viral protease with important roles in viral protein biogenesis, replication complex formation, and modulation of host ubiquitinylation and ISGylation. Herein, we use affinity purification-mass spectrometry to study the host-viral protein-protein interactome of nsp3 from five coronavirus strains: pathogenic strains SARS-CoV-2, SARS-CoV, and MERS-CoV; and endemic common-cold strains hCoV-229E and hCoV-OC43. We divide each nsp3 into three fragments and use tandem mass tag technology to directly compare the interactors across the five strains for each fragment. We find that few interactors are common across all variants for a particular fragment, but we identify shared patterns between select variants, such as ribosomal proteins enriched in the N-terminal fragment (nsp3.1) dataset for SARS-CoV-2 and SARS-CoV. We also identify unique biological processes enriched for individual homologs, for instance nuclear protein important for the middle fragment of hCoV-229E, as well as ribosome biogenesis of the MERS nsp3.2 homolog. Lastly, we further investigate the interaction of the SARS-CoV-2 nsp3 N-terminal fragment with ATF6, a regulator of the unfolded protein response. We show that SARS-CoV-2 nsp3.1 directly binds to ATF6 and can suppress the ATF6 stress response. Characterizing the host interactions of nsp3 widens our understanding of how coronaviruses co-opt cellular pathways and presents new avenues for host-targeted antiviral therapeutics.
Genomic environments scale the activities of diverse core promoters
Authors: Hong Clarice KY , Cohen Barak A 
Published: March 2021

AbstractA classical model of gene regulation is that enhancers provide specificity while core promoters provide a modular site for the assembly of the basal transcriptional machinery. However, examples of core promoter specificity have led to an alternate hypothesis in which specificity is achieved by core promoters with different sequence motifs that respond differently to genomic environments containing different enhancers and chromatin landscapes. To distinguish between these models, we measured the activities of hundreds of diverse core promoters in four different genomic locations and, in a complementary experiment, six different core promoters at thousands of locations across the genome. While genomic locations had large effects on expression, the intrinsic activities of different classes of promoters were preserved across genomic locations, suggesting that core promoters are modular regulatory elements whose activities are independently scaled up or down by different genomic locations. This scaling of promoter activities is non-linear and depends on the genomic location and the strength of the core promoter. Our results support the classical model of regulation in which diverse core promoter motifs set the intrinsic strengths of core promoters, which are then amplified or dampened by the activities of their genomic environments.
High Transcriptional Activity and Diverse Functional Repertoires of Hundreds of Giant Viruses in a Coastal Marine System
Authors: Ha Anh D , Moniruzzaman Mohammad , Aylward Frank O 
Published: March 2021

AbstractViruses belonging to theNucleocytoviricotaphylum are globally-distributed and include members with notably large genomes and complex functional repertoires. Recent studies have shown that these viruses are particularly diverse and abundant in marine systems, but the magnitude of actively replicatingNucleocytoviricotapresent in ocean habitats remains unclear. In this study, we compiled a curated database of 2,431Nucleocytoviricotagenomes and used it to examine the gene expression of these viruses in a 2.5-day metatranscriptomic time-series from surface waters of the California Current. We identified 145 viral genomes with high levels of gene expression, including 90Imiterviralesand 49Algaviralesviruses. In addition to recovering high expression of core genes involved in information processing that are commonly expressed during viral infection, we also identified transcripts of diverse viral metabolic genes from pathways such as glycolysis, the TCA cycle, and the pentose phosphate pathway, suggesting that virus-mediated reprogramming of central carbon metabolism is common in oceanic surface waters. Surprisingly, we also identified viral transcripts with homology to actin, myosin, and kinesin domains, suggesting that viruses may use them to manipulate host cytoskeletal dynamics during infection. We performed phylogenetic analysis on the virus-encoded myosin and kinesin proteins, which demonstrated that most belong to deep-branching viral clades, but that others appear to have been acquired from eukaryotes more recently. Our results highlight a remarkable diversity of activeNucleocytoviricotain a coastal marine system and underscore the complex functional repertoires expressed by these viruses during infection.ImportanceThe discovery of giant viruses has transformed our understanding of viral complexity. Although viruses have traditionally been viewed as filterable infectious agents that lack metabolism, giant viruses can reach sizes rivalling cellular lineages and possess genomes encoding central metabolic processes. Recent studies have shown that giant viruses are widespread in aquatic systems, but the activity of these viruses and the extent to which they reprogram host physiologyin situremains unclear. Here we show that numerous giant viruses consistently express central metabolic enzymes in a coastal marine system, including components of glycolysis, the TCA cycle, and other pathways involved in nutrient homeostasis. Moreover, we found expression of several viral-encoded actin, myosin, and kinesin genes, indicating viral manipulation of the host cytoskeleton during infection. Our study reveals a high activity of giant viruses in a coastal marine system and indicates they are a diverse and underappreciated component of microbial diversity in the ocean.
Endothelial Pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure
Authors: Daneva Zdravka , Ottolini Matteo , Chen Yen-Lin , Klimentova Eliska , Shah Soham A. , Minshall Richard D. , Seye Cheikh I. , Laubach Victor E. , Isakson Brant E. , Sonkusare Swapnil K. 
Published: March 2021

AbstractPannexin 1 (Panx1) is an ATP-efflux channel that controls endothelial function in the systemic circulation. However, the roles of endothelial Panx1 in resistance-sized pulmonary arteries (PAs) are unknown. Extracellular ATP dilates PAs through activation of endothelial TRPV4 (transient receptor potential vanilloid 4) ion channels. We hypothesized that endothelial Panx1–ATP– TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 or TRPV4 increased PA contractility and raised PAP. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1–P2Y2R–TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP.
Sortilin-related receptor is a druggable therapeutic target in breast cancer
Authors: Al-Akhrass Hussein , Pietilä Mika , Lilja Johanna , Vesilahti Ella-Maria , Anttila Johanna M. , Haikala Heidi M. , Munne Pauliina M. , Klefström Juha , Peuhu Emilia , Ivaska Johanna 
Published: March 2021

AbstractIn breast cancer, the currently approved anti-receptor tyrosine-protein kinase erbB-2 (HER2) therapies do not fully meet the expected clinical goals due to therapy resistance. Identifying alternative HER2-related therapeutic targets could offer means to overcome these resistance mechanisms. We have previously demonstrated that an endosomal sorting protein, sortilin-related receptor (SorLA), regulates the traffic and signaling of HER2 and HER3, thus promoting resistance to HER2-targeted therapy in breast cancer. This study aims to assess the feasibility of targeting SorLA using a monoclonal antibody. Our results demonstrate that anti-SorLA antibody (SorLA ab) alters the resistance of breast cancer cells to HER2 monoclonal antibody trastuzumabin vitroandin ovo. We found that SorLA ab and trastuzumab combination therapy also inhibits tumor cell proliferation and tumor cellularity in a mouse xenograft model of HER2-positive breast cancer. In addition, SorLA ab inhibits the proliferation of breast cancer patient-derived explant three-dimensional cultures. These results provide for the first time proof-of-principle that SorLA is a druggable target in breast cancer.
Structural dynamics of cytochrome P450 3A4 in the presence of substrates and cytochrome P450 reductase
Authors: Ducharme Julie , Sevrioukova Irina F. , Thibodeaux Christopher J. , Auclair Karine 
Published: March 2021

AbstractCytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme in humans and has been associated with harmful drug interactions. The activity of CYP3A4 is known to be modulated by several compounds, as well as by the electron transfer partner, cytochrome P450 reductase (CPR). The underlying mechanism of these effects however is poorly understood. We have used hydrogen-deuterium exchange mass spectroscopy (HDX-MS) to investigate the impact of CPR and three different substrates (7-benzyloxy-4-trifluoromethyl-coumarin, testosterone and progesterone) on the conformational dynamics of CYP3A4. Here, we report that interaction of CYP3A4 with substrates or with the oxidized or reduced form of CPR leads to a global rigidification of the CYP3A4 structure. This was evident from a suppression of deuterium exchange in several regions of CYP3A4, including those known to be involved in protein-protein interactions (C-helix) as well as substrate binding and specificity (B’-, E-helices and K/β1-loop). Furthermore, the bimodal isotopic distributions observed for some CYP3A4-derived peptides were drastically impacted by CPR and/or substrates, suggesting the existence of stable CYP3A4 conformational populations that are perturbed by ligand/CPR binding. The results have implications for understanding the mechanisms of allostery, ligand binding, and catalysis in CYP enzymes.
Explaining Asian growth paradox through interaction between informal and formal institutions
Authors: Chung Kee Hoon , Kim DaEun 
Published: March 2021

PurposeMuch of existing research has attempted to explain Asian Growth Paradox through formal institution – role of the government or rule of law. Therefore, this paper attempts to empirically explain the paradox with informal institution including interaction between informal and formal institutions. Two interrelated research questions summarize this research. First, how can we capture the relationship between informal and formal institutions? Then, how is that relationship different for Asian Paradox states vs non-paradox states?Design/methodology/approachTo capture the relationship between informal and formal institutions, we use Helmke and Levitsky (2004)'s framework to categorize the interaction as complementing, competing, substituting and accommodating. We perform cross-sectional regression analysis for more than 130 countries.FindingsWe find that the developed, developing and the Asian Paradox states display different patterns of interaction between informal and formal institutions. However, we also find that the interaction effect has a limited value explaining growth for most of these countries, suggesting that Helmke and Levitsky (2004)'s framework has limitations. Finally, we challenge the notion of Asian Paradox states, as countries outside of Asia also qualify as the Paradox states.Originality/valueNot much empirical effort has examined how different relationships between informal and formal institutions can explain growth internationally across countries. We show that different institutional patterns explain growth across the Paradox states and non-Paradox states.
The narrative strategies of retail spaces: a semio-ethnographic approach
Authors: Welte Jean-Baptiste , Badot Olivier , Hetzel Patrick 
Published: March 2021

Purpose
The purpose of this study is to understand how narratives are generated in stores.

Design/methodology/approach
The study design is based on ethnographies documented in 10 sports stores in the Paris region. The ethnographic method enables a precise and in situ observation of how narratives are structured. Narrative structures develop from the accommodation of the narratives specific to retailers and narratives specific to the customer.

Findings
The findings of this study identified four main narratives in retail spaces (the serial, the tale, the epic, the legend), each of which is distinguished by the commercial/non-commercial orientation of the narratives and by a superficial/in-depth modification of the narratives produced outside the store. These four narratives are characterized by the vendors’ roles and by the distinct interactions between customers and retail stores.

Research limitations/implications
The originality of this study is to propose a narrative framework for retail structures. It illustrates the fact that the narrative is not solely a product of experiential marketing, but that it may be found in any retail store. From a practical point of view, it highlights other less costly experiential narrative strategies.

Practical implications
From a practical point of view, it highlights other less costly experiential narrative strategies.

Originality/value
The original value of this study is to apply structural semiotics to analyse narratives in the store.
Drought grade assessment method based on grey cloud incidence clustering model
Authors: Luo Dang , Hu Yan , Sun Decai 
Published: March 2021

PurposeThe purpose of this paper is to establish a grey cloud incidence clustering model to assess the drought disaster degree under 15 indexes in 18 cities of Henan province.Design/methodology/approachThe grey incidence degree between each index and ideal index is used to determine the index weight and combined with the subjective weight, the comprehensive weight is given; the traditional possibility function is transformed into grey cloud possibility function by using the principle of maximum deviation and maximum entropy, which fully reflects the coexistence of multiple decision-making conclusions and constructs the grey cloud incidence clustering model.FindingsThe drought disaster degree of Henan province is divided into four grades under the selected 15 indexes. The drought grades show obvious regional differences. The risk levels of the east and southwest are higher, and the risk levels of the north and southeast are lower. This result is consistent with the study of drought disaster grades in Henan province, which shows the practicability and usefulness of the model.Practical implicationsIt provides an effective method for the assessment of drought disaster grade and the basis for formulating disaster prevention and mitigation plan.Originality/valueBy studying the method of multiattribute and multistage decision-making with interval grey number information. The objective weight model of index value is designed, and the subjective weight is given by experts. On the basis of the two, the comprehensive weight of subjective and objective combination is proposed, which effectively weakens the randomness of subjective weight and reasonably reflects the practicality of index decision-making. The time weight reflects the dynamic of the index. The traditional possibility function is transformed into the grey cloud possibility function, which effectively takes advantage of the grey cloud model in dealing with the coexistence of fuzzy information, grey information and random information. Thus, the conflict between the decision-making results and the objective reality is effectively solved. The interval grey number can make full use of the effective information and improve the accuracy of the actual information.
Brand balance: the effect of influencer brand encroachment on interactivity
Authors: Hamdan Lara , Lee Seung Hwan (Mark) 
Published: March 2021

PurposeAs social media platforms continue to have an increased presence in influencer marketing, researchers and practitioners are seeking ways to optimize the use of these platforms. The purpose of this study is to investigate the effect of brand encroachment, a level of brand's control over the promotion executed by social media influencers (SMIs), on the importance of interactivity of SMIs.Design/methodology/approachThis study examined the effect of brand encroachment on interactivity whilst examining the mediating effects of both passion and personal power. The study was an online, one-factor between-subjects design comparing high level of brand encroachment vs low level of brand encroachment.FindingsThe results of the experimental study suggest that as brand encroachment decreases, there is an increasing importance of being interactive. In addition, with lower brand encroachment, SMIs portray more personal power and passion toward the product or service being promoted.Originality/valueAs influencers create communities via increased levels of engagement, authenticity and relatability, it is of paramount importance that SMIs build relationships through interactivity in low-brand encroachment settings. Brands should offer more opportunities for SMIs to be interactive with their audience, while intrinsically building their personal power and passion as sources for these interactions.
Managerial ability and fair value accounting: evidence from nonfinancial firms
Authors: Bradley Wray , Sun Li 
Published: March 2021

Purpose
The purpose of this study is to examine the relation between managerial ability and fair value inputs (measured as fair value intensity) for nonfinancial firms.

Design/methodology/approach
This study uses regression analysis to investigate the impact of managerial ability on the level of fair value inputs.

Findings
This study finds significant and positive relations between managerial ability and use of Level 1 and Level 2 fair value inputs. On the other hand, this study finds an insignificant relation between managerial ability and Level 3 inputs.

Originality/value
The findings contribute to two research streams. To the best of the author’s knowledge, this is perhaps the first study that directly examines the link between managerial ability and fair value inputs.