bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphology and gene expression profiling provide complementary information for mapping cell state
Authors: Way Gregory P. , Natoli Ted , Adeboye Adeniyi , Litichevskiy Lev , Yang Andrew , Lu Xiaodong , Caicedo Juan C. , Cimini Beth A. , Karhohs Kyle , Logan David J. , Rohban Mohammad H. , Kost-Alimova Maria , Hartland Kate , Bornholdt Michael , Chandrasekaran Srinivas Niranj , Haghighi Marzieh , Weisbart Erin , Singh Shantanu , Subramanian Aravind , Carpenter Anne E. 
Published: October 2021

SummaryMorphological and gene expression profiling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to profile gene expression and cell morphology, respectively, we perturb A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting profiles from compound perturbations are more reproducible and show more diversity, but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOA) and gene targets, we find that the two assays provide a partially shared, but also a complementary view of drug mechanisms. Given the numerous applications of profiling in biology, our analyses provide guidance for planning experiments that profile cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.
The SAMBA tool uses long reads to improve the contiguity of genome assemblies
Authors: Zimin Aleksey V. , Salzberg Steven L. 
Published: October 2021

AbstractThird-generation sequencing technologies can generate very long reads with relatively high error rates. The lengths of the reads, which sometimes exceed one million bases, make them invaluable for resolving complex repeats that cannot be assembled using shorter reads. Many high-quality genome assemblies have already been produced, curated, and annotated using the previous generation of sequencing data, and full re-assembly of these genomes with long reads is not always practical or cost-effective. One strategy to upgrade existing assemblies is to generate additional coverage using long-read data, and add that to the previously assembled contigs. SAMBA is a tool that is designed to scaffold and gap-fill existing genome assemblies with additional long-read data, resulting in substantially greater contiguity. SAMBA is the only tool of its kind that also computes and fills in the sequence for all spanned gaps in the scaffolds, yielding much longer contigs. Here we compare SAMBA to several similar tools capable of re-scaffolding assemblies using long-read data, and we show that SAMBA yields better contiguity and introduces fewer errors than competing methods. SAMBA is open-source software that is distributed at https://github.com/alekseyzimin/masurca.
DOT1L bridges transcription and heterochromatin formation at pericentromeres
Authors: Malla Aushaq B. , Yu Haoming , Kadimi Srilekha , Lam TuKiet , Cox Andy L. , Smith Zachary D. , Lesch Bluma J. 
Published: October 2021

SummaryRepetitive DNA elements are packaged in heterochromatin, but many require bursts of transcription to initiate and maintain long-term silencing. The mechanisms by which these heterochromatic genome features are transcribed remain largely unknown. Here, we show that DOT1L, a conserved histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), has a specialized role in transcription of major satellite repeats to maintain pericentromeric heterochromatin and genome stability. We discover that H3K79me3 is enriched at repetitive elements, that DOT1L loss specifically compromises pericentromeric satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. Activation of pericentromeric repeats by DOT1L drives the first establishment of heterochromatin structures in cleavage-stage embryos and is required for preimplantation viability. Our findings uncover a vital instructive role for DOT1L as a bridge between transcriptional activation of heterochromatic repeats and maintenance of genome integrity, and illuminate global chromatin dynamics during early development.
Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase
Authors: Ji Zhejian , Li Hao , Peterle Daniele , Paulo Joao A. , Ficarro Scott B. , Wales Thomas E. , Marto Jarrod A. , Gygi Steven P. , Engen John R. , Rapoport Tom A. 
Published: October 2021

SUMMARYThe hexameric Cdc48 ATPase (p97 or VCP in mammals) cooperates with its cofactor Ufd1/Npl4 to extract polyubiquitinated proteins from membranes or macromolecular complexes for degradation by the proteasome. Here, we clarify how the Cdc48 complex unfolds its substrates and translocates polypeptides with branchpoints. The Cdc48 complex recognizes primarily polyubiquitin chains, rather than the attached substrate. Cdc48 and Ufd1/Npl4 cooperatively bind the polyubiquitin chain, resulting in the unfolding of one ubiquitin molecule (initiator). Next, the ATPase pulls on the initiator ubiquitin and moves all ubiquitin molecules linked to its C-terminus through the central pore of the hexameric double-ring, causing transient ubiquitin unfolding. When the ATPase reaches the isopeptide bond of the substrate, it can translocate and unfold both N- and C-terminal segments. Ubiquitins linked to the branchpoint of the initiator dissociate from Ufd1/Npl4 and move outside the central pore, resulting in the release of unfolded, polyubiquitinated substrate from Cdc48.
Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes
Authors: Nikalayevich Elvira , El Jailani Safia , Cladière Damien , Gryaznova Yulia , Fosse Célia , Touati Sandra A. , Buffin Eulalie , Wassmann Katja 
Published: October 2021

AbstractTo generate haploid gametes, cohesin is removed in a step-wise manner from chromosome arms in meiosis I and the centromere region in meiosis II, to segregate chromosomes and sister chromatids, respectively. Meiotic cohesin removal requires cleavage of the meiosis-specific kleisin subunit Rec8 by the protease Separase[1, 2]. In yeast, Rec8 is kept in a non-phosphorylated state by the action of PP2A-B56, which is localised to the centromere region, thereby preventing cohesin removal from this region in meiosis I[3-5]. However, it is unknown whether Rec8 has to be equally phosphorylated for cleavage, and whether centromeric cohesin protection is indeed brought about by dephosphorylation of Rec8 preventing cleavage, in mammalian meiosis. The identity of one or several potential Rec8-specific kinase(s) is also unknown. This is due to technical challenges, as Rec8 is poorly conserved preventing a direct translation of the knowledge gained from model systems such as yeast and C. elegans to mammals, and additionally, there is no turn-over of Rec8 after cohesion establishment, preventing phosphomutant analysis of functional Rec8. To address how Rec8 cleavage is brought about in mammals, we adapted a biosensor for Separase to study Rec8 cleavage in single mouse oocytes by live imaging, and identified phosphorylation sites promoting cleavage. We found that Rec8 cleavage by Separase depends on Aurora B/C kinase activity, and identified a residue promoting cleavage and being phosphorylated in an Aurora B/C kinase-dependent manner. Accordingly, inhibition of Aurora B/C kinase during meiotic maturation impairs endogenous Rec8 phosphorylation and chromosome segregation.
A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition
Authors: Soto-Feliciano Yadira M. , Sánchez-Rivera Francisco J. , Perner Florian , Barrows Douglas W. , Kastenhuber Edward R. , Ho Yu-Jui , Carroll Thomas , Xiong Yijun , Anand Disha , Soshnev Alexey , Gates Leah , Beytagh Mary Clare , Cheon David , Gu Shengqing , Liu X. Shirley , Krivtsov Andrei V. , Meneses Maximiliano , de Stanchina Elisa , Stone Richard M. , Armstrong Scott A. , Lowe Scott W. , Allis C. David 
Published: October 2021

ABSTRACTThe chromatin adaptor Menin interacts with oncogenic fusion proteins encoded byMLL1-rearrangements (MLL1-r), and small molecules that disrupt these associations are currently in clinical trials for the treatment of leukemia. By integrating chromatin-focused and genome-wide CRISPR screens with genetic, pharmacological, and biochemical approaches in mouse and human systems, we discovered a molecular switch between the MLL1-Menin and MLL3/4-UTX chromatin modifying complexes that dictates response to Menin-MLL inhibitors. We show that MLL1-Menin safeguards leukemia survival by impeding binding of the MLL3/4-UTX complex at a subset of target gene promoters. Disrupting the interaction between Menin and MLL1 leads to UTX-dependent transcriptional activation of a tumor suppressor gene-program that is crucial for a therapeutic response in murine and human leukemia. We establish the therapeutic relevance of this mechanism by showing that CDK4/6 inhibitors allow re-activation of this tumor-suppressor program in Menin-inhibitor insensitive leukemia cells, mitigating treatment resistance. The discovery of a molecular switch between MLL1-Menin and MLL3/4-UTX complexes on chromatin sheds light on novel functions of these evolutionary conserved epigenetic mediators and is particularly relevant to understand and target molecular pathways determining response and resistance in ongoing phase 1/2 clinical trials.
Molecular Insights into the Differential Dynamics of SARS-CoV-2 Variants of Concern (VOC)
Authors: Mandal Nabanita , Padhi Aditya K. , Rath Soumya Lipsa 
Published: October 2021

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected the lives and livelihood of millions of individuals around the world. It has mutated several times after its first inception, with an estimated two mutations occurring every month. Although we have been successful in developing vaccines against the virus, emergence of variants has enabled it to escape therapy. Few of the generated variants are also reported to be more infectious than the wild-type (WT). In this study, we analyze the attributes of all RBD/ACE2 complexes for the reported VOCs, namely, Alpha, Beta, Gamma, and Delta through computer simulations. Results indicate differences in orientation and binding energies of the VOCs from the WT. Overall, it was observed that electrostatic interactions play a major role in the binding of the complexes. Detailed residue level energetics revealed that the most prominent changes in interaction energies were seen particularly at the mutated residues which were present at RBD/ACE2 interface. We found that the Delta variant is one of the most tightly bound variants of SARS-CoV-2 with dynamics similar to WT. High binding affinity of RBD towards ACE2 is indicative of an increase in the viral transmission and infectivity. The details presented in our study would prove extremely useful for the design and development of effective therapeutic strategies for the emerging variants of the virus.
Thioflavin T indicates membrane potential in mammalian cells and can affect it in a blue light dependent manner
Authors: Skates Emily , Delattre Hadrien , Schofield Zoe , Asally Munehiro , Soyer Orkun S. 
Published: October 2021

ABSTRACTThe fluorescent benzothiazole Thioflavin T (ThT) has a high binding affinity to protein aggregates and is used as a marker for the study of this process, most commonly in the context of neurodegenerative disease research and diagnosis. Recently, this same dye was shown to indicate membrane potential in bacteria due to its cationic nature. This finding prompted a question whether ThT fluorescence is linked to the membrane potential in mammalian cells, which would be important for appropriate utilisation of ThT in research and diagnosis. Here, we show that ThT localises into the mitochondria of HeLa cells in a membrane-potential dependent manner. Specifically, ThT colocalised in cells with a well-established mitochondrial membrane-potential indicator Tetramethylrhodamine methyl ester (TMRM) and gave similar temporal responses as TMRM to treatment with a protonophore, carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP). Additionally, we found that presence of ThT together with exposure to blue light (λ=405 nm) exposure, but neither factor alone, caused depolarisation of mitochondrial membrane potential. This depolarisation effect was recapitulated by a mathematical model implementing the potential-dependent distribution of ThT and its light-dependent binding in mitochondria. These results show that ThT can act as a membrane potential dye in mammalian cells, when used at low concentrations and with low blue-light exposure, while it causes dissipation of the mitochondrial membrane potential at higher concentrations and in the presence of blue light excitation. This conclusion motivates a re-evaluation of ThT’s use at micromolar range in live-cell analyses, while indicating that this dye can enable future studies on the potential connections between membrane potential dynamics and protein aggregation.
Changing brands and impacts on Las Vegas: messages for Asian gambling destinations
Authors: Marie Jamieson Lynn , Howell Brandon Douglas , Siu Lam Carlos 
Published: October 2021

PurposeThe purpose of this study was to discover, qualitatively, periods of involvement in Las Vegas gambling marketing campaigns and analyze success factors that may be useful to other gambling destinations, particularly in the Asian market.Design/methodology/approachThe study was established to allow a two-pronged approach of semi-structured interviews and site analysis coupled with review of planning and marketing documents in Las Vegas, Nevada 1980–2000 era and ending with the 2019 branding approach.FindingsResults revealed degrees of success and rationales for changes in campaigns over a 40-year period. When analyzing market strategies, it became evident that many factors were involved decisions to visit Las Vegas, such as social, safety and security factors, as well as opportunities for recreation.Research limitations/implicationsGaining access to top level executives proved challenging due to reluctance of subjects wanting to disclose business strategies.Originality/valueThis study was unique in employing qualitative processes to elicit planning and marketing approaches and relative successes or failures from those involved in multi-property management. Further, analysis of documents over a wide time frame provided insight into the pitfalls and strengths associated with various campaigns.
A remanufacturing inventory model to control the carbon emission using cap-and-trade regulation with the hexagonal fuzzy number
Authors: Arora Ritu , Singh Anubhav Pratap , Sharma Renu , Chauhan Anand 
Published: October 2021

PurposeThe awareness for protecting the environment has resulted in remanufacturing and recycling policies in manufacturing industries. Carbon emission is one of the most important elements affecting the environment. Carbon emission due to production and transportation creates complicated situations for the manufacturing firms by affecting the manufacturer's carbon quota. The ecological consequences posed in a reverse logistic model are the subject of this study.Design/methodology/approachThe present study explores the fuzzy model of economic production for both remanufacturing and recycling with uncertain cost parameters under the cap-and-trade rule to control the carbon emission due to different modes of transportation. Due to imprecise cost parameters, the hexagonal fuzzy numbers are set to fuzzify the overall cost, which leads to correct decisions in a more confident way. The result is defuzzified by using graded mean integration.FindingsThis study offers an explicit condition to control the carbon emission of the manufacturer and reduce the optimum cost. The findings indicate that the collection of used goods that can be remanufactured must be increased. The model is validated numerically. Sensitivity analysis explores the various aspects of different parameters on net cost to accomplish the fuzzy production model.Originality/valueUnder fuzzy inference, the research offers a relevant contribution in the field of recycling with controlling carbon emission by using the cap-and-trade policy. This study provides a trading strategy for a manufacturer's decision to avoid losses.
The effects of misinformation on COVID-19 vaccine hesitancy in Bangladesh
Authors: Mahmud Md. Rifat , Bin Reza Raiyan , Ahmed S.M. Zabed 
Published: October 2021

Purpose
The main purpose of this study is to assess the prevalence of COVID-19 vaccine hesitancy among the general population in Bangladesh and the role of misinformation in this process.

Design/methodology/approach
An online survey was conducted to assess COVID-19 vaccine hesitancy among ordinary citizens. In addition to demographic and vaccine-related information, a five-point Likert scale was used to measure vaccine-related misinformation beliefs and how to counter them. Chi-square tests were used to examine the relationship between demographic variables and vaccine acceptance. A binary logistic regression analysis was conducted to identify vaccine hesitancy by different demographic groups. Nonparametric Mann–Whitney and Kruskal–Wallis tests were performed to determine the significance of difference between demographic groups in terms of their vaccine-related misinformation beliefs. Finally, the total misinformation score was computed to examine the correlation between vaccine hesitancy and the total score.

Findings
This study found that nearly half of the respondents were willing to receive COVID-19 vaccine, whereas more than one third of the participants were unsure about taking the vaccine. Demographic variables (e.g., gender, age and education) were found to be significantly related to COVID-19 vaccine acceptance. The results of binary logistic regression analysis showed that respondents who were below 40 years of age, females and those who had lower education attainments had significantly higher odds of vaccine hesitancy. There were significant differences in participants’ vaccine-related misinformation beliefs based on their demographic characteristics, particularly in the case of educational accomplishments. A highly significant negative correlation was found between total misinformation score and vaccine acceptance.

Research limitations/implications
The survey was conducted online, and therefore, it automatically precluded non-internet users from completing the survey. Further, the number of participants from villages was relatively low. Overall, the results may not be representative of the entire population in Bangladesh.

Practical implications
The findings of this paper could guide government agencies and policymakers in devising appropriate strategies to counter COVID-related misinformation to reduce the level of vaccine hesitancy in Bangladesh.

Originality/value
To the authors’ best knowledge, this study is the first to measure the level of COVID-19 vaccine hesitancy and the influence of misinformation in this process among the general public in Bangladesh.
Envisioning the future of technology integration for accessible hospitality and tourism
Authors: Tlili Ahmed , Altinay Fahriye , Altinay Zehra , Zhang Ye 
Published: October 2021

PurposeThis study aims to examine a topic of growing significance to hospitality and tourism scholars and practitioners – how emerging technologies can fulfill accessible hospitality and tourism services for people with disabilities.Design/methodology/approachA systematic review of the literature based on the Web of Science database and qualitative research were conducted. Specifically, bibliometric analysis and thematic analyzes of expert interviews were used. The obtained views from experts in the field further validated and enriched the obtained findings.FindingsThe primary topics of exploration in existing literature were identified, such as social networks and data-empowered services. The potential areas of further advances are also revealed such as the need for cross-country collaborations and potential gaps between scholarly and practitioner interest in the topic.Research limitations/implicationsThis research is limited by the scope of adopted search keywords and databases.Practical implicationsThis study offers vital practical implications for the future integration of emerging technologies to fulfill accessible hospitality and tourism. It also demonstrates the pressing need for more interconnected global collaborations for this important initiative.Social implicationsThis study emphasizes how the hospitality and tourism industry could better leverage technological power to empower people with disabilities. It also points out the importance of an inclusive process for technology implementation for accessible hospitality and tourism services to fully represent the interests of disabled customers (including the consideration of their different backgrounds).Originality/valueThis study sheds light on the future research directions of technological empowerment of accessible hospitality/tourism. It also makes methodological contributions by demonstrating what bibliometric analysis has to offer to relevant fields of studies. The solicited views of experts in the field from different countries on the topic further add to the depth and value of the findings while demonstrating the combination of these two approaches as a promising mixed-methods route to produce richer and more robust findings.
The impact of customer knowledge management, TQM and marketing capabilities on product innovation performance of Malaysian SMEs: an empirical study
Authors: Yusr Maha Mohammed , Mokhtar Sany Sanuri Mohd , Perumal Selvan , Salimon Maruf Gbadebo 
Published: October 2021

Purpose
Several strategies and processes can help companies to enhance the success rate of new products. This study aims to identify a few strategies for that purpose represented by total quality management (TQM) practices, building knowledge and capabilities. Moreover, the current paper discusses the role of applying TQM practices and customer knowledge management in developing the marketing capabilities of the organizations.

Design/methodology/approach
This study is a quantitative approach where the data collected from 141 manufacturing small and medium enterprises operating in Malaysia and partial least squares technique was used to test the hypotheses.

Findings
The findings of this study highly support all the proposed hypotheses and establish marketing capabilities as a facilitator in the relationship between TQM practices, customer knowledge management and product innovation performance. However, customer knowledge management and TQM were found not to have an impact on product innovation performance.

Originality/value
The introduced model contributes to enhancing the understanding of the impact of customer knowledge on the success of product innovation performance. The model further includes TQM as a process that helps the organization get customer satisfaction information. The incorporation of these two processes will support the organization’s capabilities in the innovation field.