bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies
Authors: Dinnon Kenneth H. , Leist Sarah R. , Okuda Kenichi , Dang Hong , Fritch Ethan J. , Gully Kendra L. , De la Cruz Gabriela , Evangelista Mia D. , Asakura Takanori , Gilmore Rodney C. , Hawkins Padraig , Nakano Satoko , West Ande , Schäfer Alexandra , Gralinski Lisa E. , Everman Jamie L. , Sajuthi Satria P. , Zweigart Mark R. , Dong Stephanie , McBride Jennifer , Cooley Michelle R. , Hines Jesse B. , Love Miriya K. , Groshong Steve D. , VanSchoiack Alison , Phelan Stefan J. , Liang Yan , Hether Tyler , Leon Michael , Zumwalt Ross E. , Barton Lisa M. , Duval Eric J. , Mukhopadhyay Sanjay , Stroberg Edana , Borczuk Alain , Thorne Leigh B. , Sakthivel Muthu K. , Lee Yueh Z. , Hagood James S. , Mock Jason R. , Seibold Max A. , O’Neal Wanda K. , Montgomery Stephanie A. , Boucher Richard C. , Baric Ralph S. 
Published: February 2022

AbstractCOVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
ATPase activity of B. subtilis RecA affects the dynamic formation of RecA filaments at DNA double strand breaks
Authors: Hernández-Tamayo Rogelio , Steube Niklas , Heimerl Thomas , Hochberg Georg , Graumann Peter L. 
Published: February 2022

ABSTRACTRecA plays a central role in DNA repair and is a main actor involved in homologous recombination (HR). In vivo, RecA forms filamentous structures termed “threads”, which are essential for HR, but whose nature is still ill defined. We show that RecA from Bacillus subtilis having lower ATP binding activity can still form nucleoprotein filaments in vitro, and still retains most of wild type RecA activity in vivo. Contrarily, loss of ATPase activity strongly reduces formation of nucleoprotein filaments in vitro, and effectivity to repair double strand breaks (DSBs) in vivo. While lowered ATP-binding activity only moderately affected RecA dynamics, loss of ATPase activity lead to a large reduction of the formation of threads, as well as of their dynamic changes observed in a seconds-scale. Single molecule tracking of RecA revealed incorporation of freely diffusing and non-specifically DNA-bound molecules into filaments upon induction of a single DSB. This change of dynamics was highly perturbed in the absence of ATPase activity, revealing that filamentous forms of RecA as well as their dynamics depend on ATPase activity. Our data suggest that RecA/ssDNA filaments change in subcellular localization and length involving ATP-driven homology search.
Polysome-CAGE of TCL1-driven chronic lymphocytic leukemia revealed multiple N-terminally altered epigenetic regulators and a translation stress signature
Authors: Ogran Ariel , Havkin-Solomon Tal , Becker-Herman Shirley , David Keren , Shachar Idit , Dikstein Rivka 
Published: February 2022

AbstractThe transformation of normal to malignant cells is accompanied by substantial changes in gene expression programs through diverse mechanisms. Here we examined the changes in the landscape of transcription start sites (TSSs) and alternative promoter (AP) usage and their impact on the translatome in TCL1-driven chronic lymphocytic leukemia (CLL). Our findings revealed a marked elevation of APs in CLL cells from Eµ-Tcl1 transgenic mice, which are particularly enriched with intragenic promoters that generate N-terminally truncated or modified proteins. Intragenic promoter activation is mediated by (i) loss of function of ‘closed chromatin’ epigenetic regulators due to the generation of inactive N-terminally modified isoforms or reduced expression; (ii) upregulation of transcription factors, including c-Myc, targeting the intragenic promoters and associated enhancers. Exogenous expression of Tcl1 in MEFs is sufficient to induce intragenic promoters of epigenetic regulators and promote c- Myc expression. We further found a dramatic translation downregulation of transcripts bearing CNY cap-proximal tri-nucleotides, reminiscent of cells undergoing metabolic stress. These findings uncovered the role of Tcl1 oncogenic function in altering promoter usage and mRNA translation in leukemogenesis.
Mapping Protein-Protein Interactions Using Data-Dependent Acquisition Without Dynamic Exclusion
Authors: Zhang Shen , Larsen Brett , Colwill Karen , Wong Cassandra J. , Youn Ji-Young , Gingras Anne-Claude 
Published: February 2022

AbstractSystematic analysis of affinity-purified samples by liquid chromatography coupled to mass spectrometry (LC-MS) requires high coverage, reproducibility, and sensitivity. Data-independent acquisition (DIA) approaches improve the reproducibility of protein-protein interaction detection by alleviating the stochasticity of data-dependent acquisition (DDA). However, the need for library generation and lack of multiplexing capabilities reduces their throughput, and analysis pipelines are still being optimized. In previous work using cell lysates, a fast MS/MS acquisition method with no dynamic exclusion (noDE) provided a comparable number of identifications and more accurate MS/MS intensity-based quantification than an optimized DDA method with dynamic exclusion (DE). Here, we have further optimized the noDE strategy for the analysis of protein-protein interactions and show that it provides better sensitivity and identifies more high confident interactors than the optimized DDA with DE and DIA approaches.TOC
A gradient border model for cell fate decisions at the neural plate border
Authors: Thiery Alexandre , Buzzi Ailin Leticia , Hamrud Eva , Cheshire Chris , Luscombe Nicholas , Briscoe James , Streit Andrea 
Published: February 2022

AbstractThe vertebrate ‘neural plate border’ is a transient territory located at the edge of the neural plate containing precursors for all ectodermal derivatives: the neural plate; neural crest; placodes; and epidermis. Elegant functional experiments in a range of vertebrate models have provided an in-depth understanding of gene regulatory interactions within the ectoderm. However, these experiments conducted at tissue level raise seemingly contradictory models for fate allocation of individual cells. Here, we carry out single cell RNA sequencing of chick ectoderm from primitive streak to neurulation stage, to explore cell state diversity and heterogeneity. We characterise the dynamics of gene modules containing key factors known to regulate ectodermal cell fates, allowing us to model the order in which these fates are specified. Furthermore, we find that genes previously classified as neural plate border specifiers typically exhibit dynamic expression patterns and are biased towards either placodal or neural crest fates, revealing that the neural plate border should be seen as an anatomical region of the ectoderm and not a discrete transcriptional state. Through co-expression of placodal and neural crest markers, we identify a population of border located unstable progenitors (BLUPs) which gradually reduces in size as fate segregation occurs. Considering our findings, we propose a ‘gradient border’ model for cell fate choice at the neural plate border, with the probability of cell fate allocation closely tied to the spatiotemporal positioning of cells.
AreTomo: An integrated software package for automated marker-free, motion-corrected cryo-electron tomographic alignment and reconstruction
Authors: Zheng Shawn , Wolff Georg , Greenan Garrett , Chen Zhen , Faas Frank G. A. , Bárcena Montserrat , Koster Abraham J. , Cheng Yifan , Agard David 
Published: February 2022

AbstractAreTomo, an abbreviation for Alignment and Reconstruction for Electron Tomography, is a GPU accelerated software package that fully automates motion-corrected marker-free tomographic alignment and reconstruction in a single package. By correcting in-plane rotation, translation, and importantly, the local motion resulting from beam-induced motion from tilt to tilt, AreTomo can produce tomograms with sufficient accuracy to be directly used for subtomogram averaging. Another major application is the on-the-fly reconstruction of tomograms in parallel with tilt series collection to provide users with real-time feedback of sample quality allowing users to make any necessary adjustments of collection parameters. Here, the multiple alignment algorithms implemented in AreTomo are described and the local motions measured on a typical tilt series are analyzed. The residual local motion after correction for global motion was found in the range of ±80 Å, indicating that the accurate correction of local motion is critical for high-resolution cryo-electron tomography (cryoET).
Highly efficient generation of isogenic pluripotent stem cell models using prime editing
Authors: Li Hanqin , Busquets Oriol , Verma Yogendra , Syed Khaja Mohieddin , Kutnowski Nitzan , Pangilinan Gabriella R. , Gilbert Luke , Bateup Helen , Rio Donald C. , Hockemeyer Dirk , Soldner Frank 
Published: February 2022

SUMMARYThe recent development of prime editing (PE) genome engineering technologies has the potential to significantly simplify the generation of human pluripotent stem cell (hPSC)-based disease models. PE is a multi-component editing system that uses a Cas9-nickase fused to a reverse transcriptase (nCas9-RT) and an extended PE guide RNA (pegRNA). Once reverse transcribed, the pegRNA extension functions as a repair template to introduce precise designer mutations at the target site. Here, we systematically compared the editing efficiencies of PE to conventional gene editing methods in hPSCs. This analysis revealed that PE is overall more efficient and precise than homology-directed repair (HDR) of site-specific nuclease-induced double-strand breaks (DSBs). Specifically, PE is more effective in generating heterozygous editing events to create autosomal dominant disease-associated mutations. By stably integrating the nCas9-RT into hPSCs we achieved editing efficiencies equal to those reported for cancer cells, suggesting that the expression of the PE components, rather than cell-intrinsic features, limit PE in hPSCs. To improve the efficiency of PE in hPSCs, we optimized the delivery modalities for the PE components. Delivery of the nCas9-RT as mRNA combined with synthetically generated chemically-modified pegRNAs and nicking guide RNAs (ngRNAs) improved editing efficiencies up to 13-fold compared to transfecting the prime editing components as plasmids or ribonucleoprotein particles (RNPs). Finally, we demonstrated that this mRNA-based delivery approach can be used repeatedly to yield editing efficiencies exceeding 60% and to correct or introduce familial mutations causing Parkinson’s disease in hPSCs.
The impact of hyperglycemia upon BeWo trophoblast cell metabolic function: A multi-OMICS and functional metabolic analysis
Authors: Easton Zachary JW , Luo Xian , Li Liang , Regnault Timothy RH 
Published: February 2022

AbstractPre-existing and gestationally-developed diabetes mellitus have been linked with impaired metabolic function in placental villous trophoblast cells, that is thought to underlie the development of metabolic diseases early in the lives of the exposed offspring. Previous research using placental cell lines and ex vivo trophoblast preparations have highlighted hyperglycemia as an important independent regulator of placental function. However, it is poorly understood if hyperglycemia directly influences aspects of placental metabolic function, including nutrient storage and mitochondrial respiration, that have been found to be impaired in diabetic placentae. Therefore, the current study examined metabolic and mitochondrial function as well as nutrient storage in both undifferentiated cytotrophoblast and differentiated syncytiotrophoblast BeWo cells cultured under hyperglycemia conditions (25 mM glucose) for 72 hours to further characterize the direct impacts of placental hyperglycemic exposure. Hyperglycemic-exposed BeWo trophoblasts displayed increased triglyceride and glycogen nutrient stores. However, specific functional readouts of metabolic enzyme activity and mitochondrial oxidative respiratory activity were not altered. We speculated that increased glycogen content may reduce free glucose available for oxidation and subsequently protect trophoblast cells from mitochondrial damage during acute high glucose exposures. To further characterize the impacts of independent hyperglycemia, the current study subsequently utilized a multi-omics approach and evaluated the transcriptomic and metabolomic signatures of BeWo cytotrophoblasts. Hyperglycemic exposure was associated with an altered transcriptomic profile (e.g. increased expression of ACSL1 (+1.36 fold-change (FC), HSD11B2 (+1.35 FC), and RPS6KA5 (+1.32 FC)), and metabolome profile (e.g. increased levels lactate (+2.72 FC), malonate (+3.74 FC), and riboflavin (+3.68 FC)) in BeWo cytotrophoblasts that further highlighted trophoblast metabolic function is modulated independently by hyperglycemia. Overall, these results demonstrate that hyperglycemia is an important independent regulator of key areas of placental metabolic function and nutrient storage, and these data continue to expand our knowledge on the mechanisms governing the development of placental dysfunction.
A setup for millisecond time-resolved X-ray solution scattering experiments at the CoSAXS beamline at the MAX IV Laboratory
Authors: Berntsson Oskar , Terry Ann E. , Plivelic Tomás S. 
Published: February 2022

The function of biomolecules is tightly linked to their structure, and changes therein. Time-resolved X-ray solution scattering has proven a powerful technique for interrogating structural changes and signal transduction in photoreceptor proteins. However, these only represent a small fraction of the biological macromolecules of interest. More recently, laser-induced temperature jumps have been introduced as a more general means of initiating structural changes in biomolecules. Here we present the development of a setup for millisecond time-resolved X-ray solution scattering experiments at the CoSAXS beamline, primarily using infrared laser light to trigger a temperature increase, and structural changes. We present results that highlight the characteristics of this setup along with data showing structural changes in lysozyme caused by a temperature jump. Further developments and applications of the setup are also discussed.
Accounting for the Nazi Aryanisation of German banks
Authors: Twyford Erin Jade , Funnell Warwick 
Published: February 2022

PurposeThis study examines how accounting practices used by Deutsche Bank could conceal its role in the destruction of Jewish financial life (bios) as part of the Nazis' Aryanisation policy to eliminate Jews from German business as a prelude to their annihilation.Design/methodology/approachThis study uses a close-reading method that draws upon a wide range of primary and secondary sources. The study is informed by Giorgio Agamben's theorisations on the state of exception and the duality of the example and exception.FindingsThe successful implementation of the Nazis' corporative economic model necessitated the cooperation of Aryan businesses to instrumentalise the financially exploitative process of Aryanisation. Accounting was part of the Nazi-Deutsch rhetoric used to disguise expropriation of Jewish businesses and other assets and, thereby, facilitate the eradication of the financial bios of Jews who owned German banks. Unknown to the Nazi authorities, Deutsche Bank, while a significant medium for Aryanisation, sought to ameliorate the long-term effects on Jewish owners, thereby recognising that not all those within Nazi Germany were fully committed disciples of Nazism.Research limitations/implicationsThe findings of this study identify how accounting practices were part of a Nazi policy designed to eliminate Jews from the German economy. The use of accounting as a form of “Nazi-Deutsch” functioned to disguise Aryanisations. The importance of these contributions of accounting practices calls for further research into the role of business and accounting in the attempted eradication of people.Originality/valueThe paper is the first to consider the process of Aryanisation in Nazi Germany (1933–1945) as a specific historiographical subject. Presented through the examination of the Aryanisation actions of Deutsche Bank, this study demonstrates the tension between Nazi ideology, the capitalist model and the culpability of accounting practices as a means to reinterpret morality to create the exception that allowed the Nazis to effectively remove all legal protections for Jews.
The effect of perceived fit on thriving at work in a Chinese context
Authors: Liu Yuxin , Li Shujie , Zhang Jianwei , Wang Shuai 
Published: February 2022

Purpose
The purpose of this paper is to investigate the effect of perceived fit on thriving and reveal the potential moderator and mediator of this effect by drawing on self-determination theory. Moreover, to adapt the research to Chinese contexts, a four-factor conceptualization of perceived fit is suggested.

Design/methodology/approach
The paper includes two studies. Study 1 involved a survey that collected data from 531 employees to investigate the relationship between perceived fit and thriving and the moderating role of personal goal commitment. Study 2 consisted of a scenario-based experiment in which 240 university students were recruited to strengthen the main findings of Study 1 and test the underlying mechanisms of the effect of perceived fit on thriving.

Findings
Study 1 shows that perceived fit positively relates to thriving, and personal goal commitment plays a moderating role in this effect. In addition, it demonstrates the validity of the proposed four-factor conceptualization of perceived fit in Chinese contexts. Study 2 strengthens the proposition of the positive effect of perceived fit on thriving and identifies the mediating roles of self-determination in this effect.

Originality/value
This paper contributes to the literature on thriving and fit by exploring new antecedents of thriving and extending the dimensions of perceived fit.
Robin hood insurance broking: driving growth with differentiation
Authors: Kumar Jitender , Singh Animesh , Gupta Ashish 
Published: February 2022

Learning outcomes
Students will have the opportunity to learn about differentiation strategy, business plans, strengths, weaknesses, opportunities and threats analysis. The primary objective is to allow students to evaluate Abhishek Singh’s decisions. After working through the case and assignment questions, students will be able to: understand the competitive landscapes in the Indian insurance broking market. Differentiate between selling and marketing. Understand the importance and application of differentiation strategy in the Indian insurance broking market. Emphasize the importance of value proposition in developing a competitive advantage for insurance broking organization. Critically analyze the internal strength and weaknesses of an insurance broking company.

Case overview/synopsis
RHIBPL, one of India’s largest insurance broking companies, operating for more than 12 years and has had a strong presence in eight major cities of India. RHIBPL had been known for life insurance, non-life insurance like cars, two-wheelers, Mediclaim and health. RHIBPL’s unique selling proposition was the best fit for each product and service after understanding the customer’s need. On October 16, 2020, Abhishek Singh, CDO at RHIBPL, was preparing for an upcoming management meeting on the company’s vision “to be the largest insurance provider in the country and to reach US$ 140 million by 2025,” which was communicated by the Ajay Bansal, founder and chief executive officer of RHIBPL. Singh had to prepare an action plan to achieve the RHIBPL’s vision. He had to develop and implement a differentiation strategy to achieve the RHIBPL’s vision from the available resources. How can he create a competitive advantage for RHIBPL in the highly competitive insurance broking market?

Complexity academic level
The case delineates the challenges facing an insurance broker company to achieve its new corporate vision. This case can be discussed in undergraduate and postgraduate courses (at the introductory level) in the business management discipline to understand the importance and application of differentiation strategy and competitive advantage. This case can also be significant for insurance-related courses for postgraduates and executives working in the insurance industry. The case can be useful for the courses on services marketing, strategic management, strategic marketing management and marketing management.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 8: Marketing.
Desired and obtained work values across 37 countries: a psychology of working theory perspective
Authors: Baranik Lisa E. , Wright Natalie , Smith Rachel W. 
Published: February 2022

PurposeMany contemporary career theories emphasize the role of individual agency and choice, a perspective that may not be relevant for the careers of underprivileged groups around the world. The psychology of working theory notes this disconnect and highlights the role that contextual variables play in the careers of marginalized, disadvantaged groups of employees. The goal of this paper was to identify factors that impact employees' careers by examining the relationship between desired work values and obtained work values.Design/methodology/approachThe data utilized in this study were from the International Social Survey Programme (ISSP) Work Orientations IV survey. Across 37 countries, 27,527 individuals were surveyed and multilevel moderation analyses were employed.FindingsUsing psychology of working theory as a theoretical framework, the authors identify the contextual factors that enable employees to secure their desired work values. Employees living in countries with higher levels of the Human Development Index have an easier time securing their desired intrinsic work values. Gender was not a statistically significant moderator.Originality/valueThe authors’ findings indicate that, for many employees, careers are influenced by larger socioeconomic factors, showing that individuals have a more difficult time shaping their own careers in some contexts.