bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring a diverse world of effector domains and amyloid signaling motifs in fungal NLR proteins
Authors: Wojciechowski Jakub W. , Tekoglu Emirhan , Gąsior-Głogowska Marlena , Coustou Virginie , Szulc Natalia , Szefczyk Monika , Kopaczyńska Marta , Saupe Sven J. , Dyrka Witold 
Published: March 2022

AbstractNLR proteins are intracellular receptors constituting a conserved component of the innate immune system of multicellular organisms. In fungi, NLRs are characterized by high diversity of architectures and presence of amyloid signaling. Here, we explore the diverse world of effector and signaling domains of fungal NLRs using state-of-the-art bioinformatic methods including MMseqs2 for fast clustering, probabilistic context-free grammars for sequence analysis, and AlphaFold2 deep neural networks for structure prediction. In addition to substantially improving the overall annotation, especially in basidiomycetes, the study identifies novel domains and reveals the structural similarity of MLKL-related HeLo- and Goodbye-like domains forming the most abundant superfamily of fungal NLR effectors. Moreover, compared to previous studies, we found several times more amyloid motifs, including novel families, and validated aggregating and prion-forming properties of the most abundant of them in vitro and in vivo. Also, through an extensive in silico search, the NLR-associated amyloid signaling is for the first time identified in basidiomycetes. The emerging picture highlights similarities and differences in the NLR architectures and amyloid signaling in ascomycetes, basidiomycetes and other branches of life.
Long range electromagnetic effects drive protein-protein approaches: an egg of Coulomb
Authors: Niccolai Neri , Morandi Edoardo , Alocci Davide , Toccafondi Alberto , Bernini Andrea 
Published: March 2022

AbstractLiving systems cannot rely on random intermolecular approaches inside cell crowding and hidden mechanisms must be present to favor only those molecular interactions which are specifically required by biological functions. Electromagnetic messaging among proteins is here hypothesized upon the observation that charged amino acids are most commonly located in adjacent sequence positions and/or in spatial close proximity. Molecular Dynamics simulations have been used to explore possible effects arising from concerted motions of charged amino acid side chains in two protein model systems. Protein electrodynamics seems to emerge as the framework for understanding long distance protein-ligand interactions.HighlightsProtein surfaces are often occupied by nearby side chains bearing opposite charges;Coulomb interactions determine hindered reorientations of charged side chains;MD simulations suggest time scales and extents of surface charge interactions;concerted motions of electric charges can yield electromagnetic protein signaling.
Chemical and genetic screens identify new regulators of tetracycline-inducible gene expression system in mammalian cells
Authors: Colicchia Valeria , Häggblad Maria , Sirozh Oleksandra , Porebski Bartlomiej , Balan Mirela , Lidemalm Louise , Carreras-Puigvert Jordi , Hühn Daniela , Fernandez-Capetillo Oscar 
Published: March 2022

ABSTRACTThe tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated a human osteosarcoma cell line which allows for inducible expression of an EGFP-fusion of the TAR DNA-binding protein 43 (TDP-43), which has been linked to neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led to the accumulation of aggregates and limited the viability of U2OS. Using this inducible system, we conducted a chemical screen with a library that included FDA-approved drugs. While the primary screen identified several compounds that prevented TDP-43 toxicity, further experiments revealed that these chemicals abrogated doxycyclinedependent TDP-43 expression. This antagonistic effect was observed with both doxycycline and tetracycline, and in several Tet-On cell lines expressing different genes, confirming the general effect of these compounds as inhibitors of the tetR system. Using the same cell line, a genome-wide CRISPR/Cas9 screen identified epigenetic regulators such as the G9a methyltransferase or TRIM28 as potential modifiers of TDP-43 toxicity. Yet again, further experiments revealed that G9a inhibition or TRIM28 loss prevented doxycycline-dependent expression of TDP-43. Together, these results suggest that none of the medically approved drugs significantly mitigates TDP-43 toxicity, identify new chemical and genetic regulators of the tetR system, and raise awareness on the limitations of this approach to conduct chemical or genetic screenings in mammalian cells.
Rapid detection of Staphylococcus aureus and Streptococcus pneumoniae by real-time analysis of volatile metabolites
Authors: Gómez-Mejia Alejandro , Arnold Kim , Bär Julian , Singh Kapil Dev , Scheier Thomas C. , Brugger Silvio D. , Zinkernagel Annelies S. , Sinues Pablo 
Published: March 2022

ABSTRACTRapid detection of pathogenic bacteria is needed for rapid diagnostics allowing adequate and timely treatment. In this study, we aimed to evaluate the technical feasibility of Secondary Electro-Spray Ionization-High Resolution Mass Spectrometry (SESI-HRMS) as a diagnostic tool for rapid detection of bacterial infections and compare its performance with the current standard of diagnostics. We compared the time required to confirm growth of the pathogenic bacteria Staphylococcus aureus and Streptococcus pneumoniae by conventional detection by culture and MAL-DI-TOF vs. detection of specific volatile organic compounds (VOCs) produced by these human pathobionts. SESI-HRMS could consistently detect VOCs produced by S. aureus or S. pneumoniae on blood agar plates within minutes, allowing to positively identify bacteria within hours. Unique S. aureus and S. pneumoniae features were detected already at bacterial densities as low as ∼103 colony forming units. Rich mass spectral fingerprints allowed for the distinction of these two bacteria on a species and even strain level. To give an incentive towards clinical application of this technology, further analyzed 17 clinical samples previously diagnosed by conventional methods. We predominantly obtained a separation of samples which showed growth (i.e. presence of living bacteria) compared to samples with no bacterial growth (i.e. presence of dead bacteria). We conclude that SESI-HRMS allows rapid identification of unique bacterial features. Further development of real-time analysis of clinical samples by SESI-HRMS will shorten the time required for microbiological diagnosis with a high level of confidence and sensitivity and should help to improve patient’s tailored treatment.IMPORTANCEA timely identification of a pathogenic bacteria causing the infection is of pivotal importance for the initiation of an adequate antimicrobial therapy. In this regard, different technologies have been developed with the aim to achieve a highly reliable, specific, and overall fast identification of pathogenic bacteria. However, conventional diagnostic techniques still require long preprocessing times (hours to days) to acquire enough biological material for an accurate identification of the pathogen. Therefore, in this work, we aimed to further shorten the detection time of current gold standards for microbiological diagnostics by providing a system capable of a fast, sensitive and specific discrimination of different pathogenic bacteria. This system relies on the real-time mass spectrometric detection of volatile organic compounds (VOCs) produced by a given organism during its growth, potentially leading to a significant shortening of the time required to obtain a positive reliable diagnostic.
Medial septum glutamate neurons are essential for spatial goal-directed memory
Authors: Bott Jean-Bastien , Robinson Jennifer , Manseau Frederic , Gauthier-Lafrenière Etienne , Williams Sylvain 
Published: March 2022

ABSTRACTThe medial septum (MS), a brain region containing acetylcholine, GABA and glutamate neurons, is essential for learning and memory. However, whether MS glutamate neurons contribute to memory is unknown. Here, we use calcium imaging and optogenetic silencing to determine the function of MS glutamate neurons in mice performing a spatial allocentric memory navigation task. While MS glutamate neurons appeared randomly active during free exploration, two groups of glutamate neurons emerged during training in a five-arm star maze, distinguished by their peak activity. The largest group was predominantly activated before locomotion whereas the other was primarily active when mice reached the reward site. Both populations were preferentially activated for correct over incorrect trajectories. Interestingly, optogenetic silencing of MS glutamate neurons immediately before mice start navigating, induced significant spatial memory impairments. Together these results demonstrate that MS glutamate neurons heterogeneously encode navigationally relevant information and are essential for spatial learning.
Broad neutralization of SARS-CoV-2 variants by circular mRNA producing VFLIP-X spike in mice
Authors: Seephetdee Chotiwat , Bhukhai Kanit , Buasri Nattawut , Leelukkanaveera Puttipatch , Lerdwattanasombat Pat , Manopwisedjaroen Suwimon , Phueakphud Nut , Kuhaudomlarp Sakonwan , Olmedillas Eduardo , Saphire Erica Ollmann , Thitithanyanont Arunee , Hongeng Suradej , Wongtrakoongate Patompon 
Published: March 2022

AbstractNext-generation COVID-19 vaccines are critical due to the ongoing evolution of SARS-CoV-2 virus and waning duration of the neutralizing antibody response against current vaccines. The mRNA vaccines mRNA-1273 and BNT162b2 were developed using linear transcripts encoding the prefusion-stabilized trimers (S-2P) of the wildtype spike, which have shown a reduced neutralizing activity against the variants of concern B.1.617.2 and B.1.1.529. Recently, a new version of spike trimer, termed VFLIP has been suggested to possess native-like glycosylation, and greater pre-fusion trimeric stability as opposed to S-2P. Here, we report that the spike protein VFLIP-X, containing six rationally substituted amino acids to reflect emerging variants (K417N, L452R, T478K, E484K, N501Y and D614G), offers a promising candidate for a next-generation SARS-CoV-2 vaccine. Mice immunized by a circular mRNA (circRNA) vaccine prototype producing VFLIP-X elicited neutralizing antibodies for up to 7 weeks post-boost against SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). In addition, a balance in TH1 and TH2 responses was achieved by immunization with VFLIP-X. Our results indicate that the VFLIP-X delivered by circRNA confers humoral and cellular immune responses, as well as neutralizing activity against broad SARS-CoV-2 variants.
Analyzing the stock market performance of central public sector enterprises disinvested through public offering mode: Indian evidence
Authors: Mandiratta Priya , Bhalla G.S. 
Published: March 2022

PurposeThe present study aims to examine the short-term effect of disinvestment oriented IPOs and FPOs on the stock market performance of Indian central public sector enterprises (CPSEs), which divested their equity between 2000 and 2017.Design/methodology/approachThe analysis of stock price reaction is conducted for listing dates only in the case of IPOs and three different dates in the case of FPOs through the event study methodology. The three-event dates related to FPOs are public notification date (PND), issue announcement date (IAD) and price band date (PBD).FindingsOverall empirical analysis indicates that investor sentiments are generally insignificant prior to and posts the PND (first date). The second major date of announcement that is (IAD) is new information in the market and returns are found to be significantly negative across both the periods that is before and after IAD. Thus, the analysis depicts strongly negative investor sentiments in the case of IAD. These results are further substantiated by negatively significant CAR (cumulative abnormal returns) values for both the pre and post-event windows of PBD as well.Research limitations/implicationsEmpirical analysis concludes that investors do not stand a chance to gain abnormal returns through initiating positions in the stocks of CPSEs during the alternative event dates analyzed.Originality/valueSince the year 2000, disinvestment through public offering has gathered momentum, and this mode accounts for approximately 62% of the collective disinvestment funds generated by the government of India till now. But there have been very limited research studies on the market performance of disinvested CPSEs. This analysis provides new empirical evidence for the market reactions of retail investors in response to the sale of equity by the Indian government in CPSEs.
Social network analysis of the Construction Community in the anti-epidemic emergency project: a case study of Wuhan Huoshenshan Hospital, China
Authors: Wang Xiaoming , He Nanjun , Li Xiaokang 
Published: March 2022

PurposeAnti-epidemic Emergency Projects (AEEPs) have unique characteristics such as a short construction period, high-quality requirements, complex construction environment, many construction participants and many uncertain affecting factors. The purpose of this paper was to propose the establishment method for the Construction Community (CC) of AEEPs (CC-AEEPs) by analyzing the management features of AEEPs, to establish the method of the Social Network Analysis (SNA) for CC-AEEPs, and to apply this method and the framework to Wuhan Huoshenshan Hospital for their verification.Design/methodology/approachAccording to the CC theory, this paper explored the member composition and the establishment method for CC-AEEPs. The optimal management factors of CC-AEEPs were proposed by combining the management features of AEEPs and the SNA method for CC-AEEPs was further established. Finally, the applicability of the method was verified through a case study, and some countermeasures for the CC-AEEP social networks were proposed.FindingsThe establishment of CC-AEEPs is an important guarantee to complete AEEPs with top speed and high quality. Ten types of CC-AEEP members all played different but irreplaceable roles in cooperative construction, among which the Government, the Contractor, and the Supervisor had outstanding performances. The SNA method could effectively analyze the complexity and cooperative relationship among the members in four aspects. The case study of Huoshenshan Hospital validated the important role of CC-AEEP and its social network in the AEEP research providing beneficial enlightenment for the cooperative optimization path of the AEEP construction participants.Originality/valueThe new establishment method for CC-AEEPs was proposed from the perspective of “cooperation among human, society, and engineering” according to the theories of the engineering sociology and the CC. In this paper, the SNA method was applied to the research on the AEEP construction for the first time and the SNA method for CC-AEEPs was purposed. The optimal management factors of CC-AEEPs and the expansion path of the CC-AEEP social networks were proposed according to the whole-process tracking of AEEPs in Wuhan.
A qualitative research study of the tech startup journey through entrepreneurial pivoting
Authors: Sala Pavan Kumar , Philbin Simon P. , Barikzai Safia 
Published: March 2022

PurposeAs part of the entrepreneurial journey, high-tech entrepreneurs are faced with the need to develop a competitive value proposition and leverage emerging technology to strengthen the value proposition. Entrepreneurial pivoting can be adopted to address this requirement since it enables the startup to validate and refine the company’s strategy and business model. Therefore, this research study provides an empirical investigation of the pivoting concept explained in the context of the lean startup approach (LSA) and technology entrepreneurship to improve the understanding of the entrepreneurial journey for high-tech entrepreneurs.Design/methodology/approachA qualitative research method was conducted by interviewing 30 high-tech entrepreneurs across the United Kingdom to validate the theories behind the LSA and identify new insights on entrepreneurial pivoting.FindingsThe research study has validated the existing types of pivots and identified two new pivots (giving 16 in total). The study has validated the existing 11 factors that trigger a tech startup to change its direction and identified three new factors (giving 14 in total). The research study also determined that there can be a domino effect in pivoting and the value proposition can be created and sustained through pivoting.Originality/valueThis study provides empirical evidence on pivots and the factors associated with pivots. Furthermore, it helps in understanding the influence of the phases of technology entrepreneurship on pivoting. The study also discusses the challenges faced by tech startups while pursuing pivots, the domino effects in pivoting and has found evidence that pivoting eventually leads to achieving the desired results.
The impact of power and relationship commitment on customer integration: a replication and extension
Authors: Zhang Min , Zhao Xiande , Huo Baofeng , Flynn Barbara 
Published: March 2022

PurposeThis study aims to examine the relationships between power, relationship commitment and customer integration by replicating and extending Zhao et al. (2008) in China and the USA.Design/methodology/approachThis study collects data from 210 manufacturers in China and 202 manufacturers in the USA. In this study, structural equation modelling is used to analyse the data.FindingsThis study finds that normative relationship commitment is positively associated with customer integration and expert and referent power are positively associated with normative relationship commitment in China and the USA. Reward and coercive power are positively associated with instrumental relationship commitment in China, whereas referent power is negatively associated. Referent, legal legitimate and reward power are positively associated with instrumental relationship commitment in the USA, whereas expert and legitimate power are negatively associated.Originality/valueThis study provides empirical evidence on the distinct impacts of different bases of mediated and non-mediated power in China and the USA, contributing to the development of the power-relationship commitment theory. The findings also provide insights into where and when the theory applies. The results can provide guidelines for managers to adjust the use of power to improve relationship commitment and customer integration in China and the USA.
Addressing how small suppliers cope with large customers: using the dual dimension of a product portfolio and customer buying center
Authors: Lacoste Sylvie , Ben Abdelaziz Fouad , Youssef Meriem 
Published: March 2022

Purpose
This paper is about customer relationships from the perspective of small suppliers. More precisely, this paper aims to examine the relational implications through a product portfolio model with the main participants of the buying center (buyer/business manager).

Design/methodology/approach
The study first uses an in-depth qualitative data analysis to explore how elements of small suppliers’ relationship with such large customer’s main actors are affected by the nature of the product (categorized between strategic, bottleneck and non-critical items). From the results, an empirical model is drawn of small suppliers’ relational strategies in a product-centered and buyer/business manager relationship typology. To analyze the results of the empirical model, a quantitative analysis is performed, using the fuzzy set qualitative comparative analysis approach.

Findings
This study contributes to deepen the supplier–customer relationship analysis, from a product-centered and customer dyadic perspective (buyer and customer business manager). The findings highlight three different small suppliers’ relationship strategy with a different level of involvement of the different participants of the buying center.

Originality/value
Few studies so far analyze vertical asymmetric relationships from a triadic perspective composed of the small supplier, the buyer and the business manager – hence, this study contributes to unveiling some of the relationship complexity within a triad of actors and how small suppliers can navigate through this complexity according to their product or service positioning.
Marketing #neurodiversity for well-being
Authors: Go Jefferies Josephine , Ahmed Wasim 
Published: March 2022

PurposeThe purpose of this study is to develop a bottom-up segmentation of people affected by neurodiversity using Twitter data.Design/methodology/approachThis exploratory study uses content analysis of information shared by Twitter users over a three-month period.FindingsCultural currents affect how the label of “neurodiversity” is perceived by individuals, marketplace actors and society. The extent to which neurodiversity provides a positive or negative alternative to stigmatizing labels for mental disorders is shaped by differentiated experiences of neurodiversity. The authors identify five neurodiversity segments according to identifiable concerns and contextual dynamics that affect mental wellbeing. Analyzing Twitter data enables a bottom-up typology of stigmatized groups toward improving market salience.Originality/valueTo the authors knowledge, this study is the first to investigate neurodiversity using Twitter data to segment stigmatized consumers into prospective customers from the bottom-up.
Utilising dentist-dental health educator skill-mix to implement oral health promotion that better supports diverse communities
Authors: Modha Bhaven 
Published: March 2022

PurposeDentists may be seen as the most prominent figures within dentistry. Yet, a number of dental care professionals make significant contributions to the profession. The dental health educator (DHE) is one prime example. This teammate is typically a dental nurse who has achieved a post-registration qualification in oral health education (OHE). Through interactions with patients, members of the community and other pertinent stakeholders, the DHE empowers people through promoting the importance of good oral health. The purpose of this paper is to cast light on the unique and invaluable roles that DHEs can play within their organisations.Design/methodology/approachThis paper aims to share some examples of dentist-DHE collaborations, where OHE initiatives were implemented within an ethnically diverse London Borough in England.FindingsIt was found that such interprofessional, skill-mix efforts were more productive, when the dentist and DHE worked together, rather than the latter working independently.Originality/valueThere exists great potential for DHEs to act as ambassadors for their dental establishments, network and collaborate with other organisations and build worthwhile relations with other healthcare professionals and stakeholders.