bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel oncogenic transcriptional targets of mutant p53 in Esophageal Squamous Cell Carcinoma
Authors: George Sara A , Kotapalli Viswakalyan , Ramaswamy Pandilla , Kumar Raju , Gowrishankar Swarnalata , Uppin Shantveer G , Bashyam Murali D 
Published: March 2023

AbstractMissense mutations in the DNA binding domain of p53 are observed frequently in Esophageal Squamous Cell Carcinoma (ESCC). Recent studies have revealed the potentially oncogenic transcriptional networks regulated by mutant p53 proteins. However, majority of these studies have focused on common ‘hotspot’ p53 mutations while rarer mutations are poorly characterized. We had previously identifiedSMARCD1as an oncogenic transcriptional target of rare ‘non-hotspot’ p53 mutants detected from squamous cell carcinoma of the oral tongue (SCCOT). We now report the characterization of ‘non-hotspot’ p53 mutations from ESCC.In-vitrotumorigenic assays performed following ectopic-expression of ‘non-hotspot’ mutant p53 proteins caused enhancement of oncogenic properties in squamous carcinoma cell lines. Genome-wide transcript profiling of ESCC tumor samples stratified for p53 status, revealed several genes exhibiting elevated transcript levels in tumors harbouring mutant p53. Of these,ARF6, C1QBPandTRIM23were studied further due to their previously reported pro-oncogenic roles. Reverse transcription quantitative PCR (RT-qPCR) performed on RNA isolated from ESCC tumor samples revealed significant correlation ofTP53transcript levels with those of the three target genes. Ectopic expression of wild type and several mutant p53 forms followed by RT-qPCR, Chromatin affinity-purification and Promoter-luciferase assays indicated the exclusive recruitment of p53 mutants – P190T and P278L, to the target genes leading to activation of expression. Several functional assays following knockdown of the target genes revealed a significant suppression of tumorigenicity in squamous carcinoma cell lines. Rescue experiments confirmed the specificity of the knockdown. The tumorigenic effect of the genes was confirmed in nude mice xenograft assays. This study has therefore identified novel oncogenic targets of rare ‘non-hotspot’ mutant p53 proteins relevant for ESCC besides validating the functional heterogeneity of the spectrum of tumor specific p53 mutations.
Positive epistasis for fitness under monosomy: Loss of ribosomal protein stoichiometry reduces the effects of other perturbations
Authors: Tutaj Hanna , Tomala Katarzyna , Pirog Adrian , Marszałek Marzena , Korona Ryszard 
Published: March 2023

AbstractThe loss of a single chromosome in a diploid organism halves the dosage of many genes and is usually accompanied by a substantial decrease in fitness. We asked whether this decrease simply reflects the joint damage caused by individual gene dosage deficiencies. We measured the fitness effects of single heterozygous gene deletions in yeast and combined them for each chromosome. This predicted a negative growth rate, i.e. lethality, for multiple monosomies. However, monosomic strains remained alive and grew as if much (often most) of the damage caused by single mutations had disappeared, revealing an exceptionally large and positive epistatic component of fitness. We looked for functional explanations by analyzing the transcriptomes. There was no evidence of increased (compensatory) gene expression on the monosomic chromosomes. Nor were there signs of the cellular stress response that would be expected if monosomy led to protein destabilization and thus cytotoxicity. Instead, all monosomic strains showed extensive upregulation of genes encoding ribosomal proteins, but in an indiscriminate manner that did not correspond to their altered dosage. This response did not restore the stoichiometry required for efficient biosynthesis, which probably became growth limiting, making all other mutation-induced metabolic defects much less important. In general, the modular structure of the cell leads to an effective fragmentation of the total mutational load. Defects outside the module(s) currently defining fitness lose at least some of their relevance, producing the epiphenomenon of positive interactions between individually negative effects.
Viruses in deep-sea cold seep sediments harbor diverse survival mechanisms and remain genetically conserved within species
Authors: Peng Yongyi , Lu Zijian , Pan Donald , Shi Ling-Dong , Zhao Zhao , Liu Qing , Zhang Chuwen , Jia Kuntong , Li Jiwei , Hubert Casey R.J. , Dong Xiyang 
Published: March 2023

AbstractDeep sea cold seep sediments have been discovered to harbor novel, abundant, and diverse bacterial and archaeal viruses. However, little is known about viral genetic features and evolutionary patterns in these environments. Here, we examined the evolutionary ecology of viruses across active and extinct seep stages in the area of Haima cold seeps in the South China Sea. Diverse antiviral defense systems in 487 microbial genomes spanning 43 families inform the dynamics of host-virus interactions. Accordingly, a total of 338 viral operational taxonomic units are identified and linked to 36 bacterial and archaeal phyla. Cold seep viruses are predicted to harbor diverse adaptive strategies to persist in this environment, including counter-defense systems, reverse transcriptases, auxiliary metabolic genes, and alternative genetic code assignments. Extremely low nucleotide diversity is observed in cold seep viral populations, being influenced by factors including microbial host, sediment depth and cold seep stage. Most cold seep viral genes are under strong purifying selection with trajectories that differ depending on whether cold seeps are active or extinct. This work sheds light on the understanding of environmental adaptation mechanisms and evolutionary patterns of viruses in the sub-seafloor biosphere.
Engagement in science content via online video leveraging television science fiction (Star Trek: Discovery)
Authors: Noor Mohamed A. F. , Manturuk Kim 
Published: March 2023

ABSTRACTUsing science fiction stories to teach real-world science concepts may improve student engagement and motivate creativity. Here, we explore the effectiveness of a science outreach video leveraging interest in science fiction television content at engaging an audience self-selected through online social media. We find that responding audience members report knowledge gains, that the science-fiction connection increased their interest, and that many may not have viewed this science content without the science-fiction connection. Overall, these findings support the use of fictional narrative connections to engage with non-student learners around science topics, extending the findings from classroom settings to online videos.
Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors
Authors: Pohl Fabian , Seufert Florian , Chung Yin Kwan , Volke Daniela , Hoffmann Ralf , Schöneberg Torsten , Langenhan Tobias , Hildebrand Peter W. , Sträter Norbert 
Published: March 2023

AbstractThe GAIN domain is a hallmark of adhesion G-protein coupled receptors (aGPCRs) as this extracellular domain contains an integral agonistic sequence (Stachel) for activation via binding to the 7-transmembrane helical (7TM) domain of the receptor. Many aGPCRs are autoproteolytically cleaved at the GPCR proteolysis site (GPS) site within the GAIN domain formed HXS/T sequence motif. However, other aGPCR can be activated without GPS cleavage. We determined the crystal structure of the human ADGRB2/BAI2 hormone receptor (HormR) and GPCR autoproteolysis-inducing (GAIN) domains and found that this aGPCR is resistant to autoproteolysis despite the presence of a canonical HLS sequence motif at the GPS. We used structural comparisons and molecular dynamics (MD) simulations to identify structural determinants that are important for autocleavage beyond the canonical HXS/T motif. These studies characterized a conserved glycine residue and an edge-π interaction of the histidine base of the GPS sequence with a phenylalanine residue that is highly conserved in cleavage-competent aGPCRs. The MD simulations showed that this interaction is important to position the imidazole group of the histidine for deprotonation of the serine or threonine nucleophile. Removal of this interaction reduced autoprote-olytic activity in the ADGRL1 receptor and restored cleavage competence of the ADGRB3 receptor in a R866H/L821F double mutant. Conservation analysis indicates that wild-type ADGRB2 and ADGRB3 are auto-cleavage-incompetent receptors.
Magnesium ions mediate ligand binding and conformational transition of the SAM/SAH riboswitch
Authors: Hu Guodong , Zhou Huan-Xiang 
Published: March 2023

ABSTRACTThe SAM/SAH riboswitch binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) with similar affinities. Mg2+is generally known to stabilize RNA structures by neutralizing phosphates, but how it contributes to ligand binding and conformational transition is understudied. Here, extensive molecular dynamics simulations (totaling 120 μs) identified over 10 inner-shell Mg2+ions in the SAM/SAH riboswitch. Six of them line the two sides of a groove to widen it and thereby pre-organize the riboswitch for ligand entry. They also form outer-shell coordination with the ligands and stabilize an RNA-ligand hydrogen bond, which effectively diminish the selectivity between SAM and SAH. One Mg2+ion unique to the apo form maintains the Shine-Dalgarno sequence in an autonomous mode and thereby facilitates its release for ribosome binding. Mg2+thus plays vital roles in SAM/SAH riboswitch function.
A CA1 circuit motif that signals the start of information integration
Authors: Heldman Raphael , Pang Dongyan , Zhao Xiaoliang , Wang Yingxue 
Published: March 2023

AbstractIntegrating information from the recent past is critical for guiding predictions and shaping behavior. The process of integrating information, such as tracking distance traveled or time elapsed, begins with establishing a starting point. Yet, the mechanisms by which neural circuits utilize relevant cues to initiate integration remain unknown. Our study sheds light on this question by identifying a subpopulation of CA1 pyramidal neurons called PyrDown. These neurons shut down their activity at the beginning of distance or time integration and then gradually ramp up their firing as the animal approaches the reward. PyrDown neurons provide a mechanism for representing integrated information through ramping activity, complementing the well-known place/time cells that respond to specific distances or time points. Our findings also reveal that parvalbumin inhibitory interneurons mediate the shutdown of PyrDown neurons, uncovering a circuit motif that enables the initiation of subsequent information integration to improve future predictions.
The effects of LED daylength extensions on the fecundity of the pest aphidMyzus persicaeand the daily activity patterns of its parasitoid,Aphidius matricariae
Authors: Fraser Jessica L. , Abram Paul K. , Dorais Martine 
Published: March 2023

AbstractSupplemental lighting, such as with LED lamps, allows greenhouse producers to maintain yields when natural light levels are low. Since both insect pests and their natural enemies are sensitive to light, both the duration and spectrum of LED daylength extensions could affect biological pest control in greenhouses. Longer days could allow for extended periods of reproduction for pests or foraging activity of biological control agents, possibly depending on the spectra used for these extensions. However, the effects of lengthening days with different LED spectra on the behaviour of biological control agents has mostly been studied in short-term experiments to date, and has not always included the context of the light’s effect on their hosts’ reproduction. In growth chambers, we examined the locomotor activity of the parasitoid biocontrol agentAphidius matricariae(Hymenoptera : Braconidae) as a predictor for foraging activity and the fecundity of its aphid hostMyzus persicae(Hemiptera : Aphididae) over multiple days under different daylength extension regimes representative of those used in greenhouse vegetable production. We compared the effects of 14, 16, 18, and 20 h photoperiods, and 12 h days extended by 6 h with three different spectral qualities. The parasitoids adjusted how their activity was distributed throughout the lit period of the day (i.e., its total duration and peak timing) without changing the total amount of daily activity, regardless of the photoperiod or the light spectrum used for daylength extension. The aphids’ peak fecundity was not affected by photoperiod or spectral quality. Our results suggest that at least some behavioral and reproductive traits of these insects can be resilient to even drastic changes in their light environment.
Diversification of Polynucleotide Kinase Clp1 Family Proteins and Their Possible Origins in Eukaryotic Evolution
Authors: Saito Motofumi , Inose Rerina , Sato Asako , Tomita Masaru , Kanai Akio 
Published: March 2023

AbstractThe Clp1 family proteins, consisting of the Clp1 and Nol9/Grc3 groups, have polynucleotide kinase (PNK) activity at the 5′ end of RNA strands and are important enzymes in the processing of some precursor RNAs. However, it remains unclear how this enzyme family diversified in the eukaryotes. We performed a large-scale molecular evolutionary analysis of the full-length genomes of 358 eukaryotic species and identified a group of protist proteins that we consider to be the evolutionary origin of Clp1 family proteins. First, we detected an average of 4.2 Clp1 family genes in members of in the protist phylum Euglenozoa, arising from gene duplication. For example, inTrypanosoma brucei, there are three genes of the Clp1 group and one gene of the Nol9/Grc3 group. In the Clp1 group proteins encoded by these three genes, the C-terminal domains have been replaced by unique characteristics domains, so we designated these proteinsTb-Clp1-t1,Tb-Clp1-t2, andTb-Clp1-t3. Experimental validation showed that onlyTb-Clp1-t2 has PNK activity against RNA strands. In a phylogenetic analysis of the PNK domain,Tb-Clp1-t2 mapped to the earliest position on the tree. Interestingly,Tb-Clp1-t1, for which no PNK activity was detected, was located on the phylogenetic tree near fungalSaccharomyces cerevisiaeClp1, which also lacks PNK activity. The analysis also revealed that in the higher eukaryotes, such as humans and plants, the Clp1 proteins diversified with the creation of isoforms by alternative splicing.
Slow release of a synthetic auxin induces formation of adventitious roots in recalcitrant woody plants
Authors: Roth Ohad , Yechezkel Sela , Serero Ori , Eliyahu Avi , Vints Inna , Tzeela Pan , Carignano Alberto , Janacek Dorina P. , Peters Verena , Kessel Amit , Dwivedi Vikas , Carmeli-Weissberg Mira , Shaya Felix , Faigenboim-Doron Adi , Ung Kien Lam , Pedersen Bjørn Panyella , Riov Joseph , Klavins Eric , Dawid Corinna , Hammes Ulrich Z. , Ben-Tal Nir , Napier Richard , Sadot Einat , Weinstain Roy 
Published: March 2023

AbstractClonal propagation of plants by induction of adventitious roots (ARs) from stem cuttings is a requisite step in breeding programs. A major barrier exists for propagating valuable plants that naturally have low capacity to form ARs. Due to the central role of auxin in organogenesis, indole-3-butyric acid (IBA) is often used as part of commercial rooting mixtures, yet many recalcitrant plants do not form ARs in response to this treatment. Here, we describe the synthesis and screening of a focused library of synthetic auxin conjugates inEucalyptus grandiscuttings and identify 4-chlorophenoxyacetic acid-L-tryptophan-OMe as a competent enhancer of adventitious rooting in a number of recalcitrant woody plants, including apple and argan. Comprehensive metabolic and functional analyses reveal that this activity is engendered by prolonged auxin signaling due to initial fast uptake and slow release and clearance of the free auxin 4-chlorophenoxyacetic acid. This work highlights the utility of a slow-release strategy for bioactive compounds for more effective plant growth regulation.
The moderating role of workplace ostracism between employee training, employee participation and organizational commitment among bank employees
Authors: Ametepe Paul Kojo , Otuaga Emetomo Uchefiho , Nnaji Chinwe Felicia , Arilesere Mustapha Sina 
Published: March 2023

PurposeThis study aimed at investigating employee training, employee participation and organizational commitment (OC) and the moderating effect of workplace ostracism among bank employees.Design/methodology/approachThe study used a descriptive and cross-sectional design with the aid of a standard scale constructed into a questionnaire. Cluster, convenience and simple random sampling techniques were used to select 1,067 respondents, of which 870 were deemed fit for the study. The theories underpinning the study were the social exchange theory (SET) and social identity theory (SIT). Four hypotheses were developed and tested using hierarchical multiple regression analysis, and moderation using PROCESS macro.FindingsThe study found that employee training and employee participation had a significant positive relationship with organizational commitment, while organizational ostracism had a significant but negative relationship with organizational commitment among bank employees. The study also found that workplace ostracism moderated the relationship between organizational climate and organizational commitment The study recommended that organizational commitment requires management training their workforce, allowing employee participation in decisions, and minimizing or outrightly eradicating the practice of organizational ostracism. It is, therefore, concluded that workers place great value on training and participation in decision-making and frown at organizational ostracism.Originality/valueThis paper fills in the gaps left by the paucity of empirical investigation of the moderating role that workplace ostracism plays between employee training, employee participation and organizational commitment – a feat that is lacking in developing countries. It serves as a reminder to management to prevent or entirely eliminate workplace ostracism to allay an employee's impression of being a threat to an organization when commitment is low.
Effect of brand experiences on brand loyalty mediated by brand love: the moderated mediation role of brand trust
Authors: Bae Byung Ryul , Kim Sung-Eun 
Published: March 2023

PurposeThe aim of this study is to examine how brand trust moderates the effect of brand experience on brand loyalty mediated by brand love in the context of Korean smartphone users. The authors examine the relationships focused on Apple iPhone and Samsung Galaxy phone.Design/methodology/approachThe authors designed the conceptual model based on theoretical and empirical background. The authors collected data using a self-administered structured questionnaire through an online research company. The authors tested the hypotheses using a structural equation modeling in AMOS and PROCESS macro model number 8 based on 598 Korean smartphone users.FindingsThe authors found that brand experiences affect brand love, and brand love affects brand loyalty. The authors found that brand experiences affect brand loyalty directly, and brand love mediated the relationship between brand experiences and brand loyalty. The authors found that brand trust had a moderating effect between brand experiences and brand love but had no moderating effect between brand experiences and brand loyalty. Finally, the authors found that brand trust has a moderated mediation role between brand experiences, brand love and brand loyalty.Originality/valueThis is the first study to examine the moderated mediation role of brand trust in the relationship between brand experiences, brand love and brand loyalty focused on Apple iPhone and Samsung Galaxy phone users in the Korean context.
A pandemic impact study on working women professionals: role of effective communication
Authors: Tripathi Shalini Nath , Sethi Deepa , Malik Nishtha , Mendiratta Aparna , Shukla Manisha 
Published: March 2023

PurposeThe study aims to develop an in-depth understanding of challenges faced by Indian women professionals during the pandemic and the human resource (HR) initiatives like effective communication, taken by the organizations to mitigate the plight of these professionals.Design/methodology/approachA mix of two qualitative research methods namely focus groups in-depth and one-to-one in-depth interviews was used. A total of 32 females working with different organizations participated.FindingsThe thematic analysis revealed themes related to challenges faced by working women-gendered burnout, mental health issues, increased household responsibilities, job insecurity, work-life conflict, gender inequalities, reduced internal communication and financial independence, domestic violence and exploitation. The major themes that emerged for the organizational initiatives were flexible working hours, equal women representation in response to planning and decision making, driving transformative change for gender equality, paid leaves for family care, caregiving bonus, leadership development seeds, increased female recruitments, transparent communication and counseling sessions.Research limitations/implicationsThe study establishes a holistic understanding of the plight of Indian women professionals and the consequent organizational interventions accompanied by transparent communication. It adds rigor to the evolving literature on COVID-19 and enriches the theoretical narrative of policy adaptations by industry practitioners for aligning them with employee needs. This helps in routing the policy design and implementation in light of the challenges faced.Originality/valueThe study presents an in-depth understanding of challenges faced by women employees; and provides a foundation for identifying human resource management (HRM) interventions customized for working females. It also proposes a framework implementable in the recovery phase, deploying critical strategic shifts like reflection, recommitment and re-engagement of the women workforce in order to maximize their efficacy for rapidly evolving organizational priorities.
Exploring the microfoundations of innovation: what they are, where they come from and where they are going?
Authors: Fernandes Cristina I. , Hughes Mathew (Mat) , Ferreira João , Veiga Pedro Mota 
Published: March 2023

PurposeMicrofoundations have received increasing attention in several management disciplines. This study aims to outline the uniqueness of microfoundations research in innovation, look at where it comes from and where it is going and provide rich opportunities for future work.Design/methodology/approachTo advance research in this area, this study conducted a systematic literature review combining mixed methods and creating a mapping framework to take stock of progress in the innovation microfoundations research field.FindingsThis study shows how distinct subfields have formed around key ideas expressed in subsets of seminal articles, shedding light on the relational nature of knowledge creation – uncovering these subfields’ characteristics, evolution and future trajectories.Originality/valueThis study develops a framework that reflects a critical analysis of the microfoundations of innovation within dos three research levels – individual, process and interaction and structure – and highlights the research gaps and potential research questions for future research that reflect the broad spectrum of approaches in the microfoundations of innovation literature.