bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversification of small RNA pathways underlies germline RNAi incompetence in wild C. elegans strains
Authors: Chou Han Ting , Valencia Francisco , Alexander Jacqueline C. , Bell Avery Davis , Deb Diptodip , Pollard Daniel A. , Paaby Annalise B. 
Published: August 2021

ABSTRACTThe discovery that experimental delivery of dsRNA can induce gene silencing at target genes revolutionized genetics research, by both uncovering essential biological processes and creating new tools for developmental geneticists. However, the efficacy of exogenous RNAi varies dramatically within the C. elegans population, raising questions about our understanding of RNAi in the lab relative to its activity and significance in nature. Here, we investigate why some wild-type strains fail to mount a robust RNAi response to germline targets. We observe diversity in mechanism: in some strains, the response is stochastic, either on or off among individuals, while in others the response is consistent but delayed. Increased activity of the Argonaute PPW-1, which is required for germline RNAi in the laboratory strain N2, rescues the response in some strains, but dampens it further in others. Among wild-type strains, genes known to mediate RNAi exhibited very high expression variation relative to other genes in the genome as well as allelic divergence and strain-specific instances of pseudogenization at the sequence level. Our results demonstrate functional diversification in the small RNA pathways in C. elegans, and suggest that RNAi processes are evolving rapidly and dynamically in nature.
Polycomb Repressive Complex 2 shields naïve human pluripotent cells from trophectoderm differentiation
Authors: Kumar Banushree , Navarro Carmen , Winblad Nerges , Schell John P , Zhao Cheng , Lanner Fredrik , Elsässer Simon J 
Published: August 2021

ABSTRACTThe first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.
Mechanistic basis for the emergence of EPS1 as a catalyst in plant salicylic acid biosynthesis
Authors: Torrens-Spence Michael P. , Li Tianjie , Wang Ziqi , Glinkerman Christopher M. , Matos Jason O. , Wang Yi , Weng Jing-Ke 
Published: August 2021

AbstractUnique to plants in the Brassicaceae family, the production of the plant defense hormone salicylic acid (SA) from isochorismate is accelerated by an evolutionarily young isochorismoyl-glutamate pyruvoyl-glutamate lyase, EPS1, which belongs to the BAHD acyltransferase protein family. Here, we report the crystal structures of apo and substrate-analog-bound EPS1 from Arabidopsis thaliana. Assisted by microsecond molecular dynamics simulations, we uncover a unique pericyclic rearrangement lyase mechanism facilitated by the active site of EPS1. We reconstitute the isochorismate-derived pathway of SA biosynthesis in Saccharomyces cerevisiae, which serves as an in vivo platform that helps identify active-site residues critical for EPS1 activity. This study describes the birth of a new catalyst in plant phytohormone biosynthesis by reconfiguring the ancestral active site of a progenitor enzyme to catalyze alternative reaction.One sentence summaryBy reconfiguring the active site of a progenitor acyltransferase-fold, EPS1 acquired the unique, evolutionarily new lyase activity that accelerates phytohormone salicylic acid production in Brassicaceae plants.
Computational modeling of virucidal inhibition mechanism for broad-spectrum antiviral nanoparticles and HPV16 capsid segments
Authors: Chaturvedi Parth , Kelich Payam , Nitka Tara A. , Vuković Lela 
Published: August 2021

AbstractSolid core nanoparticles coated with sulfonated ligands that mimic heparan sulfate proteoglycans (HSPG) can exhibit virucidal activity against many viruses that utilize HSPG interactions with host cells for the initial stages of the infection. How the interactions of these nanoparticles with large capsid segments of HSPG-interacting viruses lead to their virucidal activity has been unclear. Here, we describe the interactions between sulfonated nanoparticles and segments of the human papilloma virus type 16 (HPV16) capsids using atomistic molecular dynamics simulations. The simulations demonstrate that nanoparticles primarily bind at interfaces of two HPV16 capsid proteins. Insertions of nanoparticles at these interfaces leads to increased separation in distances and angles between capsid proteins. As the time progresses, the nanoparticle binding can lead to breaking of contacts between two neighboring proteins. The revealed mechanism of nanoparticles targeting the interfaces between pairs of capsid proteins can be utilized for designing new generations of virucidal materials and contribute to the development of new broad-spectrum non-toxic virucidal materials.Abstract Figure
Electrical activity recorded from the spinal cord in freely moving rats using a subdural bioelectronic implant
Authors: Harland Bruce , Aqrawe Zaid , Vomero Maria , Boehler Christian , Raos Brad , Asplund Maria , O’Carroll Simon J , Svirskis Darren 
Published: August 2021

SummaryBioelectronic devices have found use at the interface with neural tissue to investigate and treat nervous system disorders. Here, we present the development and characterization of a thin flexible bioelectronic implant inserted over the thoracic spinal cord in rats directly in contact with the spinal cord. There was no negative impact on hind-limb functionality nor any change in the volume or shape of the spinal cord. The bioelectronic implant was maintained in rats for a period of 3 months. We present the first subdural recordings of spinal cord activity in freely moving animals. Recordings contained multiple distinct voltage waveform shapes that were typically between 1 – 6 mV and lasted between 0.1 and 1 seconds. In the future, this implant will facilitate the identification of biomarkers in spinal cord injury and recovery, while enabling the delivery of localized treatments.
Effects of face masks and ventilation on the risk of SARS-CoV-2 respiratory transmission in public toilets: a quantitative microbial risk assessment
Authors: Denpetkul Thammanitchpol , Sittipunsakda Oranoot , Pumkaew Monchai , Mongkolsuk Skorn , Sirikanchana Kwanrawee 
Published: August 2021

AbstractPublic toilets could increase the risk of COVID-19 infection via airborne transmission; however, related research is limited. We aimed to estimate SARS-CoV-2 infection risk through respiratory transmission using a quantitative microbial risk assessment framework by retrieving SARS-CoV-2 concentrations from the swab tests of 251 Thai patients. Three virus-generating scenarios were investigated: an infector breathing, breathing with a cough, and breathing with a sneeze. Infection risk (97.5th percentile) was as high as 10−3 with breathing and increased to 10−1 with a cough or sneeze, thus all higher than the risk benchmark of 5 × 10−5 per event. No significant gender differences for toilet users (receptors) were noted. The highest risk scenario of breathing and a sneeze was further evaluated for risk mitigation measures. Risk mitigation to lower than the benchmark succeeded only when the infector and receptor simultaneously wore an N95 respirator or surgical mask and when the receptor wore an N95 respirator and the infector wore a denim fabric mask. Ventilation up to 20 air changes per hour (ACH), beyond the 12-ACH suggested by the WHO, did not mitigate risk. Virus concentration, volume of expelled droplets, and receptor dwell time were identified as the main contributors to transmission risk.Highlights-The use of public toilets poses a risk of SARS-CoV-2 respiratory transmission-Highest risks generated in the order of sneezing, coughing, and breathing-No gender differences in risk by counteracting dwell times and inhalation rates-Ventilation did not reduce risk even at 20 ACH, beyond the WHO-recommended value-N95 and surgical masks offer the most effective risk mitigation to toilet usersGraphical abstract
Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies
Authors: Haslwanter Denise , Lasso Gorka , Wec Anna Z. , Furtado Nathália Dias , Raphael Lidiane Menezes Souza , Sun Yan , Stransky Stephanie , Pedreño-Lopez Núria , Tse Alexandra , Correia Carolina Argondizo , Bornholdt Zachary A. , Sakharkar Mrunal , Avelino-Silva Vivian I. , Moyer Crystal L. , Watkins David I. , Kallas Esper G. , Sidoli Simone , Walker Laura M. , Bonaldo Myrna C. , Chandran Kartik 
Published: August 2021

SummaryThe resurgence of yellow fever in South America has prompted mitigation through vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a virulent African isolate, and their capacity to induce neutralizing antibodies against the vaccine strain is widely used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. Here, we show that antiviral potency of the polyclonal antibody response in both U.S. and Brazilian vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to genetic changes at two sites in the central domain II of the glycoprotein E, including the acquisition of an N–linked glycosylation site, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for designing updated vaccines.
MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer
Authors: Prasad Manu , Zorea Jonathan , Jagadeeshan Sankar , Shnerb Avital , Bouaoud Jebrane , Michon Lucas , Novoplansky Ofra , Badarni Mai , Cohen Limor , Yagodayev Ksenia , Tzadok Sapir , Rotblat Barak , Brezina Libor , Mock Andreas , Karabajakian Andy , Fayette Jérôme , Cohen Idan , Cooks Tomer , Allon Irit , Dimitstei Orr , Joshua Benzion , Kong Dexin , Voronov Elena , Scaltriti Maurizio , Carmi Yaron , Hess Jochen , Morris Luc G.T. , Saintigny Pierre , Elkabets Moshe 
Published: August 2021

AbstractAlthough the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Using pre-clinical HNC models, we demonstrated that treatment with the MEK1/2 blocker trametinib delays HNC initiation and progression by reducing tumor cell proliferation and enhancing the anti-tumor immunity of CD8+T cells. Further activation of CD8+T cells by supplementation with anti-programmed death-1 (αPD-1) antibody eliminated tumors and induced an immune memory in the cured mice. Mechanistically, an early response to trametinib treatment sensitized tumors to αPD-1-supplementation by attenuating the expression of tumor-derived colony-stimulating factor-1 (CSF-1), which reduced the abundance of two CSF-1R+CD11c+myeloid-derived suppressor cell (MDSC) populations in the tumor microenvironment (TME). In contrast, prolonged treatment with trametinib abolished the anti-tumor activity of αPD-1, because tumor cells undergoing the epithelial to mesenchymal transition (EMT) in response to trametinib restored CSF-1 expression and re-created an immune-suppressive TME. These findings provide the rationale for testing the trametinib/αPD-1 combination in HNC and highlight the importance of sensitizing tumors to immunotherapies by using targeted therapies to interfere with the host-tumor interaction.Graphical abstract
On the stability and layered organization of protein-DNA condensates
Authors: Latham Andrew P. , Zhang Bin 
Published: August 2021

AbstractMulti-component phase separation is emerging as a key mechanism for the formation of biological condensates that play essential roles in signal sensing and transcriptional regulation. The molecular factors that dictate these condensates’ stability and spatial organization are not fully understood, and it remains challenging to predict their microstructures. Using a near-atomistic, chemically accurate force field, we studied the phase behavior of chromatin regulators that are crucial for heterochromatin organization and their interactions with DNA. Our computed phase diagrams recapitulated previous experimental findings on different proteins. They revealed a strong dependence of condensate stability on the protein-DNA mixing ratio as a result of balancing protein-protein interactions and charge neutralization. Notably, a layered organization was observed in condensates formed by mixing HP1, histone H1, and DNA. This layered organization may be of biological relevance as it enables cooperative DNA packaging between the two chromatin regulators: histone H1 softens the DNA to facilitate the compaction induced by HP1 droplets. Our study supports near atomistic models as a valuable tool for characterizing the structure and stability of biological condensates.
Service marketing strategies and performances of tourism and hospitality enterprises: implications from a small border province in Thailand
Authors: Pholphirul Piriya , Rukumnuaykit Pungpond , Charoenrat Teerawat , Kwanyou Akkaranai , Srijamdee Kitisak 
Published: August 2021

PurposeThe objective of this study is to determine how service marketing strategies affect enterprises in the tourism and hospitality industry, especially, operators in small towns that are not tourism destinations and visited only by small numbers of tourists.Design/methodology/approachThis study investigates the impact of 4P strategy implementation on the potential and profitability of service operators in Nong Khai Province, Thailand, by using an econometric model and defining dependent variables in order to classify firm performance into 3 areas, namely, (1) revenue, (2) cost/expense and (3) profit—in log form.FindingsStudy results show that tourism and hospitality service operators have to place emphasis on “development,” starting from upstream processes such as research and development and utilizing local wisdom and reflecting cultural identities as well as focusing on downstream activities, including adoption of modern media. At the same time, operators should also emphasize marketing and sales promotions as well as seek publicity through websites and online social media in parallel with developing downstream activities.Research limitations/implicationsThis paper only focuses on Nong Khai Province as the research area because, first, Nong Khai has a relatively low income per capita and is located in Thailand's Northeast, the country's poorest region. Second, Nong Khai is a border province, adjacent to the Lao PDR, and thus there are numerous tourists from the Lao PDR and overseas countries who travel in and out of the province through the Thailand–Lao border checkpoints.Practical implicationsRelevant government agencies should provide support throughout the development process from upstream to downstream in order to upgrade the potential of tourism and service operators in this small province by incorporating local identities used for creation of service products and by supporting marketing and sales promotions whether in the form of organizing various exhibitions events, publicity via the Internet, etc.Social implicationsRaising service standards of an organization and developing an acceptable quality brand and setting fair prices without taking advantage of consumers were strategies that played important roles. This set of strategies was implemented together with a development strategy for people also through the process of team building and knowledge management, including skill development through a training system, which also played an important role toward the sustainability of tourism and hospitality enterprises in Nong Khai Province.Originality/valueIt is believed that this paper is the first study to apply Stan Shih's innovation smiling curve in a small border province of Thailand. This study could shed the light for tourism and hospitality enterprises in a small and poor town in attempt to be the sustainability.
Social networks as a vehicle for happiness management in university governance
Authors: Barquero Cabrero José Daniel , Caldevilla Domínguez David , Barrientos Báez Almudena , Gonzálvez Vallés Juan Enrique 
Published: August 2021

PurposeThis study aims to determine whether the communication of Universities in Madrid (Spain) on social networks through their official channels has caused positive results in students’ perceptions of their trust in university institutions during the first semester of the 2020–2021 term and to measure whether the implementation of happiness management strategies in the communication within university governance affected students’ happiness levels, as well as on the recognition of their belonging to the university.Design/methodology/approachWith an exploratory-correlational approach and a quantitative study, this study conducted a statistical-descriptive analysis based on the premise of a general linear regression model with correlations between the variables, using a data collection instrument, whose construct and content validity was previously assessed by experts, which was answered by 564 students of the Degrees in Communication and Marketing from the Complutense University of Madrid, University of La Laguna, and ESERP Business and Law School. The Kaiser-Meyer-Olkin test and Bartlett’s test of sphericity were implemented to analyze the correlation between variables; Cronbach’s alpha coefficient and Pearson and Spearman’s coefficients were also used.FindingsThose students who used social networks to receive news from university institutions about the COVID-19 pandemic deem these channels official, sound and credible. Similarly, the use of official information from university institutions on social networks increases students’ happiness levels.Originality/valueTo the best of the authors’ knowledge, this is one of the first studies aiming to provide scientific evidence of the relationship between happiness management and university governance. This research’s practical implications lead to attributing added value to these types of means for the university governance that seeks students’ happiness.
Managerial openness and employee voice: a moderated mediation model
Authors: Yin Yishuai , Duan Jinyun , Wang Tingxi , Jiao Xuhui 
Published: August 2021

Purpose
Drawing on a costs-benefit analysis perspective, the purpose of this paper is to investigate the relationship between managerial openness and employee voice and its boundary conditions.

Design/methodology/approach
This study collected three waves of data by surveying 326 pairs of employees and their supervisors. The hypotheses were tested by using Hayes’s (2018) SPSS macro application with a bootstrap approach to obtain confidence intervals.

Findings
Managerial openness facilitates employee voice by decreasing perceived voice costs. Felt obligation positively moderates the direct as well as the indirect relationship between perceived voice costs and employee voice.

Originality/value
This study uncovers the alternative mechanism underlying the relationship between managerial openness and employee voice as well as the boundary condition of this relationship.
Theoretical analysis of entropy generation in second grade nanofluid considering heat source/sink over a rotating disk
Authors: Javed Muhammad Faisal , Jameel Mohammed , Khan Muhammad Ijaz , Qayyum Sumaira , Khan Niaz B. , Khan Tufail Ahmad 
Published: August 2021

Purpose
This study aims to focus on second grade fluid flow over a rotating disk in the presence of chemical reaction. Uniform magnetic field is also taken into account. Because of the smaller magnetic Reynolds number, induced magnetic field is negligible. Heat equation is constructed by considering heat source/sink.

Design/methodology/approach
Suitable variables are used to transform nonlinear partial differential equations to ordinary ones. Convergent series solutions are attained by applying homotopy analysis method.

Findings
Trends of different parameters on concentration, velocity and temperature are shown graphically. Skin friction coefficient and local Nusselt number are calculated and investigated under the effect of elaborated parameters. An elevation in the value of magnetic field parameter causes collapse in the velocity distributions. Velocity distribution in increasing function of viscoelastic parameter. Temperature and concentration profiles are decreasing functions of viscoelastic parameter. Concentration distribution reduces by increasing the chemical reaction parameter. There is more surface drag force for larger M, while opposite behavior is noted for β.

Originality/value
To the best of the authors’ knowledge, such consideration is yet to be published in the literature.
RoomTetris in room committing: why the role of minimum-length-of-stay requirements should be revisited
Authors: Battiti Roberto , Brunato Mauro , Battiti Filippo 
Published: August 2021

PurposeThis study aims to analyze how different room-committing practices affect the occupancy and profitability of hotels and it critically reviews the role of minimum-length-of-stay (MLOS) requirements given these findings.Design/methodology/approachThe approach uses statistical analysis of simplified contexts to develop understanding, and simulations of more complex situations to confirm the relevance in realistic contexts.FindingsThe study demonstrates that proper solutions of the room-committing problem improve occupancy and profitability, in particular, for hotels working in high-season and high-occupancy situations. Smart committing algorithms diminish the role of MLOS requirements. More demand can be accepted without sacrificing late-arriving long reservations.Originality/valueTo the best of the authors’ knowledge, this work, building upon a previous one cited in this paper, is the first to rigorously study the room-committing problem and to demonstrate its relevance in practical situations and its implications on MLOS rules.