bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single molecule studies reveal branched pathways for activator-dependent assembly of RNA polymerase II pre-initiation complexes
Authors: Baek Inwha , Friedman Larry J. , Gelles Jeff , Buratowski Stephen 
Published: June 2021

SUMMARYRNA polymerase II (Pol II) transcription reconstituted from purified factors suggests pre-initiation complexes (PICs) can assemble by sequential incorporation of factors at the TATA box. However, these basal transcription reactions are generally independent of activators and co-activators. To study PIC assembly under more realistic conditions, we used single-molecule microscopy to visualize factor dynamics during activator-dependent reactions in nuclear extracts. Surprisingly, Pol II, TFIIF, and TFIIE can pre-assemble on enhancer-bound activators before loading into PICs, and multiple Pol II complexes can bind simultaneously to create a localized cluster. Unlike TFIIF and TFIIE, TFIIH binding is singular and dependent on the basal promoter. Activator-tethered factors exhibit dwell times on the order of seconds. In contrast, PICs can persist on the order of minutes in the absence of nucleotide triphosphates, although TFIIE remains unexpectedly dynamic even after TFIIH incorporation. Our kinetic measurements lead to a new branched model for activator-dependent PIC assembly.HIGHLIGHTSSingle molecule microscopy reveals unexpected dynamics of RNA Pol II and GTFsMultiple Pol IIs cluster on UAS/enhancer-bound activators before binding the core promoterPol II, TFIIF, and TFIIE, but not TFIIH, can pre-assemble at the UAS/enhancerActivators increase the rates of Pol II and GTF association with DNAeTOC BlurbSingle-molecule microscopy experiments by Baek et al. show that RNA polymerase II and basal transcription factors TFIIF and TFIIE preassemble on UAS/enhancer-bound activators, poised for loading into initiation complexes with TFIIH at the core promoter. Transcription activators kinetically enhance factor recruitment, creating a localized cluster of polymerases at the UAS/enhancer.
The novel Rab5 effector FERRY links early endosomes with the translation machinery
Authors: Schuhmacher J. S. , tom Dieck S. , Christoforidis S. , Landerer C. , Davila Gallesio J. , Hersemann L. , Seifert S. , Schäfer R. , Giner A. , Toth-Petroczy A. , Kalaidzidis Y. , Bohnsack K. E. , Bohnsack M. T. , Schuman E. M. , Zerial M. 
Published: June 2021

AbstractLocalized translation is vital to polarized cells and requires precise and robust distribution of different mRNAs and ribosomes across the cell. However, the underlying molecular mechanisms are poorly understood and important players are lacking. Here we show that the novel Rab5 effectorFive-subunitEndosomalRab5 andRNA/ribosome intermediarY, FERRY complex recruits mRNAs and ribosomes to early endosomes, through direct mRNA interaction. FERRY displays preferential binding to certain groups of transcripts, including mRNAs encoding mitochondrial proteins. Deletion of FERRY subunits reduces the endosomal localization of transcripts in cells and has a significant impact on mRNA and protein levels. Clinical studies show that genetic disruption of FERRY causes severe brain damage. We found that, in neurons, FERRY co-localizes with mRNA on early endosomes and mRNA loaded FERRY-positive endosomes are in close proximity of mitochondria. FERRY thus transforms endosomes into mRNA carriers and plays a key role in regulating mRNA distribution and transport.
A Machine Learning-Enabled Pipeline for Large-Scale Virtual Drug Screening
Authors: Gupta Aayush , Zhou Huan-Xiang 
Published: June 2021

AbstractVirtual screening is receiving renewed attention in drug discovery, but progress is hampered by challenges on two fronts: handling the ever increasing sizes of libraries of drug-like compounds, and separating true positives from false positives. Here we developed a machine learning-enabled pipeline for large-scale virtual screening that promises breakthroughs on both fronts. By clustering compounds according to molecular properties and limited docking against a drug target, the full library was trimmed by 10-fold; the remaining compounds were then screened individually by docking; and finally a dense neural network was trained to classify the hits into true and false positives. As illustration, we screened for inhibitors against RPN11, the deubiquitinase subunit of the proteasome and a drug target for breast cancer.TOC Graphic
Systematic evaluation of genome-wide metabolic landscapes in lactic acid bacteria reveals diet-induced and strain-specific probiotic idiosyncrasies
Authors: Koduru Lokanand , Lakshmanan Meiyappan , Lim Pei-Yu , Ho Pooi-Leng , Banu Mazlina , Park Doo-Sang , Ow Dave Siak-Wei , Lee Dong-Yup 
Published: June 2021

AbstractLactic acid bacteria (LAB) naturally occur in animal and plant niches and are well-known to elicit several health benefits in humans. Yet, how they adapt their functional metabolic landscapes to diverse nutrient environments and synthesize relevant bioactive compounds remain unexplored across genera, species and strains. Hence, presented herein is a systematic framework for comprehensively characterizing the genome-wide metabolisms of six representative LAB by combining multi-omics data within silicomodeling. We analyse the differences in their growth and cellular fitness, biosynthetic capability of health-relevant compounds, i.e., postbiotics, and probable interactions with 15 common gut microbiota under 11 virtual dietary regimes, and show such attributes are diet- and species-specific. Particularly, some LAB exhibit a desirable balance between synthesis of beneficial postbiotic compounds, positive interactions with beneficial gut commensals, and the ability to colonize and persist in gut environment. We also observe that “high fat-low carb” diets likely lead to detrimental outcomes in most LAB. Our results clearly highlight that probiotics are not “one size fits all” commodities and need to be formulated in a personalised manner for their use as dietary supplements and live biotherapeutics. Overall, the proposed framework will systematize the probiotic administration and could also widen the strain repertoire.
Ectopic expression of KRASG12D and p53R167H in porcine mammary epithelial cells results in transformation and tumorigenesis
Authors: Remmers Neeley , Carlson Mark A. 
Published: June 2021

AbstractWe describe our initial studies in the development of an orthotopic, genetically-defined, large animal model of breast cancer, using immunocompetent pigs. Primary mammary epithelial cells were isolated from the porcine gland. Primary mammary cells were immortalized with hTERT, and then transformed cell lines were generated from these immortalized cells with oncogenic KRAS and dominant negative p53. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion. Three transformed cell lines were selected based on in vitro performance, and were able to grow tumors when injected subcutaneously in nude mice, with undifferentiated morphology. Tumorigenic porcine mammary cell lines were generated in this report.
Toolkit for Oscillatory Real-time Tracking and Estimation (TORTE)
Authors: Schatza Mark J , Blackwood Ethan B , Nagrale Sumedh S , Widge Alik S 
Published: June 2021

ABSTRACTBackgroundClosing the loop between brain activity and behavior is one of the most active areas of development in neuroscience. There is particular interest in developing closed-loop control of neural oscillations. Many studies report correlations between oscillations and functional processes. Oscillation-informed closed-loop experiments might determine whether these relationships are causal and would provide important mechanistic insights which may lead to new therapeutic tools. These closed-loop perturbations require accurate estimates of oscillatory phase and amplitude, which are challenging to compute in real time.New MethodWe developed an easy to implement, fast and accurate Toolkit for Oscillatory Real-time Tracking and Estimation (TORTE). TORTE operates with the open-source Open Ephys GUI (OEGUI) system, making it immediately compatible with a wide range of acquisition systems and experimental preparations.ResultsTORTE efficiently extracts oscillatory phase and amplitude from a target signal and includes a variety of options to trigger closed-loop perturbations. Implementing these tools into existing experiments is easy and adds minimal latency to existing protocols.Comparison with Existing MethodsMost labs use in-house lab-specific approaches, limiting replication and extension of their experiments by other groups. Accuracy of the extracted analytic signal and accuracy of oscillation-informed perturbations with TORTE match presented results by these groups. However, TORTE provides access to these tools in a flexible, easy to use toolkit without requiring proprietary software.ConclusionWe hope that that the availability of a high-quality, open-source, and broadly applicable toolkit will increase the number of labs able to perform oscillatory closed-loop experiments, and will improve the replicability of protocols and data across labs.HighlightsTORTE provides a toolkit to investigate closed loop oscillation-informed experiments.The toolkit is versatile and open-source promoting replicability across scientists.The analytic signal algorithm within TORTE preforms equally to existing algorithms.
Comparative plastomics of Amaryllidaceae: Inverted repeat expansion and the degradation of the ndh genes in Strumaria truncata Jacq
Authors: Könyves Kálmán , Bilsborrow Jordan , Christodoulou Maria D. , Culham Alastair , David John 
Published: June 2021

AbstractAmaryllidaceae is a widespread and distinctive plant family contributing both food and ornamental plants. Here we present an initial survey of plastomes across the family and report on both structural rearrangements and gene losses. Most plastomes in the family are of similar gene arrangement and content however some taxa have shown gains in plastome length while in several taxa there is evidence of gene loss. Strumaria truncata shows a substantial loss of ndh family genes while three other taxa show loss of cemA, which has been reported only rarely. Our sparse sampling of the family has detected sufficient variation to suggest further sampling across the family could be a rich source of new information on plastome variation and evolution.
Quantification of RNA Polymerase I transcriptional attenuation at the active VSG expression site in Trypanosoma brucei
Authors: Weisert Nadine , Thein Klara , Reis Helena , Janzen Christian J. 
Published: June 2021

ABSTRACTThe cell surface of the extracellular pathogen Trypanosoma brucei consists of a dense coat of variant surface glycoprotein (VSG), which enables the parasite to evade the immune system of the vertebrate host. Only one VSG gene from a large repertoire is expressed from a so-called bloodstream form expression site (BES) at a given timepoint. There are several BES in every parasite but only one is transcriptionally active. Other BES are silenced by transcriptional attenuation. Periodic activation of a previously-silenced BES results in differential VSG transcription and escape from the immune response. A process called antigenic variation. In contrast to gene transcription in other eukaryotes, the BES is transcribed by RNA polymerase I (Pol I). It was proposed that this highly-processive polymerase is needed to provide a sufficiently high transcription rate at the VSG gene. Surprisingly, we discovered a position-dependent Pol I activity and attenuation of transcriptional elongation also at the active BES. Transcription rates at the VSG gene appear to be comparable to Pol II-mediated transcription of house-keeping genes. Although these findings are in contradiction to the long-standing concept of continuously high transcription rates at the active BES in Trypanosoma brucei, they are complementary to recent groundbreaking findings about transcriptional regulation of VSG genes.
Hypocrisy and legitimacy in the aftermath of a scandal: an experimental study of stakeholder perceptions of nonfinancial disclosure
Authors: Bellucci Marco , Acuti Diletta , Simoni Lorenzo , Manetti Giacomo 
Published: June 2021

PurposeThis study aims to investigate how stakeholders perceive the company's nonfinancial disclosure after a scandal has occurred. More specifically, the authors examine whether and how sustainability reporting practices in the aftermath of a scandal can influence the perceptions of stakeholders in terms of hypocrisy and legitimacy.Design/methodology/approachThe present research represents a companion paper to another study in this issue that investigates the adaptation of companies' reporting behaviors after a scandal. The results of the initial qualitative study informed the subsequent quantitative study developed in this article. The authors build on the evidence of the main paper and perform a 2 × 2 between-subjects experiment to examine how stakeholders perceive the actions of companies that aim to restore their eroded legitimacy through social, environmental and sustainability (SES) reporting.FindingsThe results suggest that when companies take responsibility and develop remedial, socially responsible corporate activities are perceived as less hypocritical and more legitimate. Moreover, we show an interaction effect between taking responsibility and developing remedial socially responsible actions on hypocrisy and legitimacy perception.Originality/valueThe present research takes advantage of an experimental design to investigate the effects of the adaptation of SES reporting from the perspective of stakeholders. The study provides insightful theoretical and practical implications for managers regarding how to handle a reputational loss and avoid perceptions of hypocrisy.
Digital-IIoTs spheres approach toward public development: an exploiting fuzzy-grey mathematical modeling of IIoTs spheres
Authors: Kang Da , Prabhu M. , Ahmed Ramyar Rzgar , Zhang Zhuo , Sahu Atul Kumar 
Published: June 2021

PurposeIn the present era, executives are shifting keenly toward industrial Internet of things (IIoTs) spheres. It is observed that IIoTs spheres become a key for each industry to grow up and bear the largest entrepreneurship opportunities globally and is linked to improve the shifting sphere of publics (SSPs). The core objective of research work is SSPs, which is nexus on secondary objectives. The authors proposed the two DSSs ( decision support systems) to full fill secondary objectives as discussing: In case of first objective, the authors proposed a fuzzy-DSS, which assists the executives to identify the weak and poor performing IIoTs spheres so that performance of IIoTs spheres can be accelerated. In case of second objective, grey-DSS aids the same executives to evaluate and benchmark alternative partner under considered IIoTs spheres so that the best partner can be chosen by company 4.0.Design/methodology/approachThe authors conducted the significant systematic literature review and realistic empirical survey in the context of industry IIoTs spheres and extract the appropriate IIoTs spheres. Next, the authors built a framework by compiling the global standardized IIoTs spheres. The framework is utilized to build the two DSSs such as fuzzy- and grey-DSS (to full fill secondary objectives). The both DSSs are simulated by acting on a case study. The authors implemented the fuzzy set coupled with degree of similarity approach on proposing framework as a part of first case-objective and hybrid technique accompanied with grey set on same framework as a part of second case-objective, respectively.FindingsA South African automobile parts manufacturing company is investigated as a case study company 4.0 for the prototype testing and simulation of DSSs. The performance gaps are computed and measured by subtracting each sphere's weight of functional units (FUs) from evaluated ideal weight. The weak performing spheres and FUs are suggested to be improved in future as a part of first objective. Next, A3 parts supplier/partner is advised as the best alternative by simulating the grey-DSS under IIoTs framework as a part of second case-objective. Both secondary objectives (two DSSs) are framed to attain the core objective (SSPs).Originality/valueAs discussed, the core objective of research work is to attain the SSPs, linked to secondary objectives. The research work integrates the knowledge and thinking of SSPs as well as IIoTs researchers to create the novel mathematical and statistical IIoTs in focusing on advance SSPs networks. The research work is momentous for entire Industry 4.0 companies, which troubles to bear more entrepreneurship opportunities (improving the SSPs) at global standard.
Social entrepreneurship and cultural contextualization: a review
Authors: Pounder Paul Alexander 
Published: June 2021

Purpose
This study aims to provide insights into the conceptualization of social entrepreneurship and the extent to which culture affects it.

Design/methodology/approach
First, social entrepreneurship is conceptualized and then the research integrates Hofstede’s framework, with some consideration for Inglehart’s and Schwartz’s framework in exploring the effects of cultural values.

Findings
Seminal studies on social entrepreneurship delineated acting entrepreneurially and having a social mission but failed to consider cultural contextualization. After illustrating Hofstede’s, Inglehart’s and Schwartz’s frameworks for cultural dimensions, the research shows that different cultural dimensions can provide a better understanding of social entrepreneurship.

Research limitations/implications
This study has a limited scope as it relies on narrow conceptualizations of social entrepreneurship and culture.

Practical implications
Future national agendas should embrace varying notions of shared obligation across support institutions and enterprises as they attempt to address social problems across differing cultures.

Originality/value
This research contributes to the literature by providing an insightful understanding of the influence of culture on social entrepreneurship through integrating widely used cultural dimensions.
Exploring awareness and application of disaster risk management cycle (DRMC) from stakeholder's perspective
Authors: Ahmad Basri Siti Aisyah , Syed Zakaria Sharifah Akmam , A.Majid Taksiah , Yusop Zulkifli 
Published: June 2021

Purpose
The disaster risk management cycle (DRMC) is a part of the important efforts designed to handle disaster risk. DRMC contains the following four phases: response, recovery, mitigation and preparedness. This paper aims to determine the awareness of stakeholder on DRMC and to explore the application of DRMC from stakeholder’s perspective.

Design/methodology/approach
Disaster is an extreme event that causes heavy loss of life, properties and livelihood. Every year, Malaysia has been affected by disasters, whether natural or manmade. DRM is the management of resources and the responsibility for dealing with all aspects of an emergency. An effective DRM requires a combination of knowledge and skills. Questionnaires were distributed to the construction industry players and flood victims.

Findings
Results obtained on the basis of the survey revealed that a majority of respondents are unaware of DRMC. In addition, combination of professional and non-professional respondent’s perspectives in each phase of DRMC and effects of disaster are presented by the hierarchy.

Originality/value
The study of DRMC is commonly about the explanation or comparison of the concept but infrequently in the application of the DRMC. This study will fill the gap between theory and application of DRMC. The study aimed to determine whether the construction industry player and community aware of DRMC and to explore DRMC of flood event from perspective of industry players and flood victims. From this comparison, the management can create a better cycle of disaster management to handle various type disaster and to anticipate disaster risks.
Green supply chain management and organizational culture: a bibliometric analysis based on Scopus data (2001-2020)
Authors: El Baz Jamal , Iddik Sadia 
Published: June 2021

Purpose
Along with rapid development in the green supply chain fields, questions have been raised about the direct effects of internal and external drivers. Recent evidence suggest that organizational culture is a prerequisite for the understanding of green supply chain management (GSCM). However, there has been limited examination of organizational culture in the green supply chain research area. The purpose of this paper is to understand the relationship between green supply chain management (GSCM) and organizational culture.

Design/methodology/approach
To do so, a bibliometric analysis is carried out. The search was conducted in the Scopus database by using different keywords. The records found were scanned and refined bringing the total number of documents to 46. A descriptive analysis covering influential authors, leading journals, contributing organizations and most popular words used in titles and keywords, using the Biblioshiny app, followed by a content analysis have been conducted.

Findings
The findings show the following: most of the influential studies were conducted by only a few researchers. The publications within the field started to increase during 2012–2020. It is worth mentioning, that the USA and UK universities have a strong research contribution among all, and there are seven core publishing journals that lead the field such as cleaner of production and sustainability. The content analysis revealed some aspects and shed light on two main topics: organizational culture as a driver or a barrier toward GSCM; and the organizational culture contribution role on the impact of GSCM on performance.

Research limitations/implications
This paper only addresses GSCM with organizational culture based on a small sample of papers. Furthermore, this study needs to be expanded with empirical research on the topic. It would be interesting to assess the effects of national culture within the same research area. More broadly, researchers may also need to explore the various databases instead of focusing only on Scopus database case of this paper, using various keywords.

Practical implications
This study plays an important role for managers and firms, and also this study is contributing in increasing the understanding of the role of cultural factors on implementing the GSCM practices and getting the highest benefits from it.

Originality/value
This paper holds significant contribution for scholars, especially for those who are interested in cultural issues within the management field, and for managers by enlightening a critical element to concentrate on for the betterment of green sustainability within their firms. Considering this, future research suggestions are identified.