bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir
Authors: Krismer Laura , Schöppe Helge , Rauch Stefanie , Bante David , Sprenger Bernhard , Naschberger Andreas , Costacurta Francesco , Fürst Anna , Sauerwein Anna , Rupp Bernhard , Kaserer Teresa , von Laer Dorothee , Heilmann Emmanuel 
Published: December 2023

AbstractThe Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an epidemic, zoonotically emerging pathogen initially reported in Saudi Arabia in 2012. MERS-CoV has the potential to mutate or recombine with other coronaviruses, thus acquiring the ability to efficiently spread among humans and become pandemic. Its high mortality rate of up to 35 % and the absence of effective targeted therapies call for the development of antiviral drugs for this pathogen. Since the beginning of the SARS-CoV-2 pandemic, extensive research has focused on identifying protease inhibitors for the treatment of SARS-CoV-2. Our intention was therefore to assess whether these protease inhibitors are viable options for combating MERS-CoV. To that end, we used previously established protease assays to quantify inhibition of the SARS-CoV-2 and MERS-CoV main proteases. Furthermore, we selected MERS-CoV-Mpromutants resistant against nirmatrelvir, the most effective inhibitor of this protease, with a safe, surrogate virus-based system, and suggest putative resistance mechanisms. Notably, nirmatrelvir demonstrated effectiveness against various viral proteases, illustrating its potential as a broad-spectrum coronavirus inhibitor. To adress the inherent resistance of MERS-CoV-Mproto ensitrelvir, we applied directed mutagenesis to a key ensitrelvir-interacting residue and provided structural models.One-Sentence SummaryWe investigate antivirals for MERS-CoV with a pool of SARS-CoV-2 antiviral drugs and study potential resistances developing against those drugs.
Symmetry-adapted Markov state models of closing, opening, and desensitizing in α7 nicotinic acetylcholine receptors
Authors: Zhuang Yuxuan , Howard Rebecca J. , Lindahl Erik 
Published: December 2023

Abstractα7 nicotinic acetylcholine receptors (nAChRs) are homopentameric ligand-gated ion channels gated by acetylcholine. These receptors play crucial roles in controlling electrical signaling within the nervous system by facilitating the passage of cations across the membrane. Recent studies have resolved and functionally annotated closed, open, and desensitized states of α7 nAChRs, providing insight into ion permeation and lipid modulation. However, the process by which α7 nAChRs transition between states remains unclear. To understand gating and lipid modulation, we generated two ensembles of molecular dynamics simulations of the apo form of α7 nAChRs, with or without cholesterol. Using symmetry-adapted Markov state modeling, we developed a five-state gating model. Free energies recapitulated functional behavior, with the closed state dominating in the absence of agonists. Notably, the transition rate from open to a non-conductive intermediate (flipped) state corresponded to experimentally measured open durations around 0.1 ms. The introduction of cholesterol relatively stabilized the desensitized state and reduced barriers between desensitized and open states. These results establish plausible asymmetric transition pathways between functionally important states, they define lipid modulation effects in the α7 nAChR conformational cycle, and provide an ensemble of structural models that could be utilized for guiding rational design strategies to develop lipidic pharmaceuticals targeting these receptors.
Understanding how genetically encoded tags affect phase separation by Heterochromatin Protein HP1α
Authors: Zhou Ziling (Kate) , Narlikar Geeta J. 
Published: December 2023

AbstractLiquid-liquid phase separation (LLPS) is driven by weak multi-valent interactions. Such interactions can result in the formation of puncta in cells and dropletsin vitro. The heterochromatin protein HP1α forms droplets with chromatinin vitroand is found in puncta in cells. A common approach to visualize the dynamics of HP1α in cells is to genetically encode fluorescent tags on the protein. HP1α modified with tags such as GFP has been shown to localize to dynamic punctain vivo. However, whether tagged HP1α retains its intrinsic phase separation properties has not been systematically studied. Here, using different C-terminal tags (AID-sfGFP, mEGFP, and UnaG), we assessed how tag size and linker length affected the phase separation ability of HP1α with DNAin vitro. We found that the AID-sfGFP tag (52 kDa) promoted HP1α phase-separation, possibly driven by the highly disordered AID degron. The mEGFP tag (27 kDa) inhibited phase-separation by HP1α, whereas an UnaG tag (13 kDa) with a 16 amino acid linker showed minimal perturbation. The UnaG tag can thus be used in cellular studies of HP1α to better correlatein vitroandin vivostudies. To test if cellular crowding overcomes the negative effects of large tagsin vivo, we used polyethylene glycol (PEG) to mimic crowdingin vitro. We found that addition of 10% PEG8000 or PEG4000 enables phase separation by GFP-tagged HP1α at comparable concentrations as untagged HP1α. However, these crowding agents also substantially dampened the differences in phase-separation between wild-type and mutant HP1α proteins. PEG further drove phase-separation of Maltose Binding Protein (MBP), a tag often used to solubilize other proteins. These results suggest that phase-separation of biological macromolecules with PEG should be interpreted with caution as PEG-based crowding agents may change the types of interactions made within the phases.
Cross-linguistic and acoustic-driven effects on multiscale neural synchrony to stress rhythms
Authors: He Deling , Buder Eugene H. , Bidelman Gavin M. 
Published: December 2023

ABSTRACTWe investigated how neural oscillations code the hierarchical nature of stress rhythms in speech and how stress processing varies with language experience. By measuring phase synchrony of multilevel EEG-acoustic tracking and intra-brain cross-frequency coupling, we show the encoding of stress involves different neural signatures (delta rhythms = stress foot rate; theta rhythms = syllable rate), is stronger for amplitude vs. duration stress cues, and induces nested delta-theta coherence mirroring the stress-syllable hierarchy in speech. Only native English, but not Mandarin, speakers exhibited enhanced neural entrainment at central stress (2 Hz) and syllable (4 Hz) rates intrinsic to natural English. English individuals with superior cortical-stress tracking capabilities also displayed stronger neural hierarchical coherence, highlighting a nuanced interplay between internal nesting of brain rhythms and external entrainment rooted in language-specific speech rhythms. Our cross-language findings reveal brain-speech synchronization is not purely a “bottom-up” but benefits from “top-down” processing from listeners’ language-specific experience.HighlightsNeural oscillations at delta and theta bands synchronize with stress and syllable rhythms.Hierarchical delta-theta phase coupling mirrors speech rhythm hierarchy.Language experience shapes multiscale brain-to-speech entrainment.Optimized brain-to-speech synchronization occurs at natural stress (2 Hz) and syllable (4 Hz) rates.Amplitude cues dominate the neural oscillatory encoding of stress rhythm.
Cell-type-specific 3D-genome organization and transcription regulation in the brain
Authors: Liu Shiwei , Zheng Pu , Wang Cosmos Yuqi , Jia Bojing Blair , Zemke Nathan R. , Ren Bing , Zhuang Xiaowei 
Published: December 2023

Abstract3D organization of the genome plays a critical role in regulating gene expression. However, it remains unclear how chromatin organization differs among different cell types in the brain. Here we used genome-scale DNA and RNA imaging to investigate 3D-genome organization in transcriptionally distinct cell types in the primary motor cortex of the mouse brain. We uncovered a wide spectrum of differences in the nuclear architecture and 3D-genome organization among different cell types, ranging from the physical size of the cell nucleus to the active-inactive chromatin compartmentalization and radial positioning of chromatin loci within the nucleus. These cell-type-dependent variations in nuclear architecture and chromatin organization exhibited strong correlation with both total transcriptional activity of the cell and transcriptional regulation of cell-type-specific marker genes. Moreover, we found that the methylated-DNA-binding protein MeCP2 regulates transcription in a divergent manner, depending on the nuclear radial positions of chromatin loci, through modulating active-inactive chromatin compartmentalization.
The impacts of caterpillar fungus income on grazing pressure in Tibetan regions: a tale of income diversification
Authors: Kang Qi , Carpio Carlos E. , Wang Chenggang , Tang Zeng 
Published: December 2023

PurposeThis research examined the impacts of diversified income from trading caterpillar fungus on pastoral households' livestock production and income. The specific objectives were to identify the main factors underlying participation in caterpillar fungus trade and to explore the impacts of a diversified income from trading fungus on livestock production activities and income.Design/methodology/approachData were collected from a pastoral household survey (n = 503) in five Tibetan Autonomous Prefectures. The authors employed propensity score matching (PSM) procedures to estimate the effects of participation in trading caterpillar fungus.FindingsPastoral households participating in caterpillar fungus activities maintain smaller herds, sell fewer animals for profit, slaughter more livestock for family consumption and experience fewer livestock deaths compared to nonparticipants. There is also some evidence that pastoral households participating in caterpillar fungus activities have a higher annual income compared to nonparticipants.Research limitations/implicationsA direct measure of grassland degradation was not included due to the data limitation. The estimated average treatment effects could differ under different observed households' characteristics.Originality/valueThis study fills a gap in the literature on the impacts of diversified income on livestock production activities. The authors provide a new perspective on the controversy over the extraction of caterpillar fungus. This study contributes to exploring the dual role of income diversification in addressing poverty and grassland resource degradation for Tibetan pastoral communities.
Students’ perception of strategies for effective lean knowledge in future Nigerian construction industry
Authors: Aka Adefemi , Isah Abubakar Danladi , Salisu Olusegun Idris , Bello Abdulkabir Opeyemi 
Published: December 2023

Purpose
Waste has been a major challenge in the construction industry. Lean concepts have been adopted in developed nations to overcome waste. However, developing countries are still faced with the challenge due to a lack of strategies for effective lean knowledge by construction practitioners. The purpose of this research is to identify the strategies for lean knowledge in the future Nigerian construction industry.

Design/methodology/approach
This was achieved through a case study of a Nigerian university. Assignments and questionnaires were the two instruments used for data collection in the study. Content analysis was adopted to analyse the data obtained from the assignments, while statistical tools such as correlation and ANOVA analysis were used to analyse the questionnaire data.

Findings
The findings of the study showed that the introduction of lean theory into students’ academic curriculum, lean practical classes and collaboration between universities, industry and lean construction institutes are some of the critical strategies for adequate lean knowledge in the future Nigerian construction industry.

Research limitations/implications
The study is case-based and focused on a single university. The study did not also put clients’ level of lean knowledge as well as future required acquaintance into consideration.

Practical implications
This study is important as it will enable students to have an adequate understanding of the concept of lean construction right from a higher institution level. This study will enable students to put the knowledge into practice in the construction industry, hence eliminating waste or NVAAs in future construction projects.

Originality/value
The findings of the study could enhance concerted efforts by universities, lean construction institutes and the construction industry towards an intentional and systematic delivery of lean knowledge that will reduce waste in future Nigerian construction projects. Further studies should be carried out to identify the success factors required by clients for effective lean knowledge in construction projects.
How do illegitimate tasks affect hospitality employees’ adaptive performance? An explanation from the perspective of cognitive-affective system theory of personality
Authors: Li Pengbo , Lv Yina , Wang Runna , Chen Tao , Gao Jing , Huang Zixin 
Published: December 2023

Purpose
Guided by the cognitive-affective system theory of personality (CAPS), this study aims to investigate the parallel mediating effects of cognitive and affective cynicism on the relationship between illegitimate tasks and employees’ adaptive performance. It also proposes growth need strength as a moderating variable for relationships between illegitimate tasks and employees’ adaptive performance.

Design/methodology/approach
Using a time-lagged design, data were gathered from 330 frontline hotel employees in China.

Findings
The authors found that the presence of illegitimate tasks is negatively associated with employees’ adaptive performance, this relationship being mediated by cognitive and affective cynicism. Growth need strength weakens the negative impacts of cognitive and affective cynicism on employees’ adaptive performance. In addition, the indirect effect of illegitimate tasks on employees’ adaptive performance via cognitive and affective cynicism is stronger for employees with lower levels of growth need strength.

Practical implications
Hotel managers must heed the negative impact of illegitimate tasks. Furthermore, they should underscore the importance of promoting a harmonious and positive organizational culture and atmosphere. Naturally, hotel managers must also establish effective communication with employees, assisting them in fostering a desire for excellence in their work.

Originality/value
This study provides valuable insights for the hospitality industry by investigating how illegitimate tasks hold sway over hotel employees’ adaptive performance. The study uses a moderated dual-path model to uncover the mechanisms behind this impact and the influence of boundary conditions, thereby expanding the understanding of the topic.
Climate change adaptation through nature-based solution: examining the case of Thakurani Khal of Mongla Port Municipality, Bagerhat Bangladesh
Authors: Chowdhooree Imon , Aziz Tasfin , Rashid Md. Jubaer , Hossain Meherab 
Published: December 2023

Purpose
Urban areas, especially in the coastal region of Bangladesh, face environmental degradation due to rapid urbanization, uncontrolled socio-economic activities and experiencing the adverse impacts of climate change. Nature-based solutions (NbS) as options for restoring, preserving, maintaining and elevating natural features or systems are becoming popular for reducing vulnerabilities caused either by natural hazards or human-induced activities. With this understanding, this study aims to explore the need of practicing NbS by studying the condition of a tidal canal (known as Thakurani Khal) and its peripheral areas of Mongla Port Municipality, a coastal and seaport town in Bangladesh.

Design/methodology/approach
This case study-based research uses multiple inquiries, including focus group discussions, pair-wise comparison, observation, GIS-based mapping, key informant interviews and secondary climate data review, to understand the spatial development of the area and community reactions to the changes in the urban environment.

Findings
The natural water flow of this canal is controlled by sluice gates that indirectly allowed the dweller to encroach its lands and convert the canal into a solid waste dumping area. These human-induced activities as well as the climate change-induced events (i.e. extreme heat, intensive and irregular rainfall, increased number of cyclones, etc.) have made the adjacent areas prone to waterlogging and drainage congestion. In this context, the revival of the original natural quality of the canal has been identified as an alternative to ensuring an adaptive urban environment.

Originality/value
This research highlights the importance of practicing NbS for developing urban resilience in the context of climate change.
Meeting the needs of students in higher education multigenerational classrooms: what can educators do?
Authors: Schnell-Peskin Lauren , Riley Gina , Hodnett Kristen , Gryta Virginia , Kisamore April 
Published: December 2023

PurposeIt is now considered commonplace to teach in a multigenerational higher education classroom that is made up of Baby Boomers, Generation X, Y and Z students. To ensure that all students, regardless of their generational identity, are successful in the classroom, educators must teach purposefully, with an understanding of the variables that affect student learning. Educators must ensure instruction is delivered according to varying student strengths and needs. This paper will provide guidance for higher education faculty teaching in multigenerational classrooms by reviewing the strengths and weaknesses across student generations. The most effective instructional practices for teaching will be discussed.Design/methodology/approachThis article is a literature review focused on meeting the needs of multigenerational learners in synchronous and asynchronous online learning classrooms.FindingsTo ensure that all students, regardless of generational identity, are successful in the classroom, educators must teach purposefully, with an understanding of the variables that affect student learning. A summary of these generational strengths and needs are discussed within this paper.Practical implicationsThis paper will provide guidance for higher education faculty teaching in multigenerational classrooms by reviewing the strengths and weaknesses across student generations.Originality/valueThis paper will provide guidance for higher education faculty teaching in multigenerational classrooms by reviewing the strengths and weaknesses across student generations. The most effective instructional practices for teaching will be discussed.
Crack localization in glass fiber composite beams by experimental modal analysis and multi variable Gaussian process regression method
Authors: Rama Krishna S. , Sathish J. , Rahul Mani Datta Talari , Raghu Vamsi S. 
Published: December 2023

PurposeEnsuring the early detection of structural issues in aircraft is crucial for preserving human lives. One effective approach involves identifying cracks in composite structures. This paper employs experimental modal analysis and a multi-variable Gaussian process regression method to detect and locate cracks in glass fiber composite beams.Design/methodology/approachThe present study proposes Gaussian process regression model trained by the first three natural frequencies determined experimentally using a roving impact hammer method with crystal four-channel analyzer, uniaxial accelerometer and experimental modal analysis software. The first three natural frequencies of the cracked composite beams obtained from experimental modal analysis are used to train a multi-variable Gaussian process regression model for crack localization. Radial basis function is used as a kernel function, and hyperparameters are optimized using the negative log marginal likelihood function. Bayesian conditional probability likelihood function is used to estimate the mean and variance for crack localization in composite structures.FindingsThe efficiency of Gaussian process regression is improved in the present work with the normalization of input data. The fitted Gaussian process regression model validates with experimental modal analysis for crack localization in composite structures. The discrepancy between predicted and measured values is 1.8%, indicating strong agreement between the experimental modal analysis and Gaussian process regression methods. Compared to other recent methods in the literature, this approach significantly improves efficiency and reduces error from 18.4% to 1.8%. Gaussian process regression is an efficient machine learning algorithm for crack localization in composite structures.Originality/valueThe experimental modal analysis results are first utilized for crack localization in cracked composite structures. Additionally, the input data are normalized and employed in a machine learning algorithm, such as the multi-variable Gaussian process regression method, to efficiently determine the crack location in these structures.
Influence of V doping on the microstructure, chemical stability, mechanical and tribological properties of MoS2 coatings
Authors: Lu Xiaolong , Sui Xudong , Zhang Xiao , Yan Zhen , Hao Junying 
Published: December 2023

Purpose
This study aims to investigate the effect of V doping on the microstructure, chemical stability, mechanical and vacuum tribological behavior of sputtered MoS2 coatings.

Design/methodology/approach
The MoS2-V coatings are fabricated via tuning V target current by magnetron sputtering technique. The structural characteristic and elemental content of the coatings are measured by field emission scanning electron microscopy, X-ray diffractometer, electron probe X-ray micro-analyzer, Raman, X-ray photoelectron spectroscopy, high resolution transmission electron microscope and energy dispersive spectrometer. The hardness of the deposited coatings are tested by a nanoindentation technique. The vacuum tribological properties of MoS2-V coatings are studied by a ball-on-disc tribometer.

Findings
Introducing V into the MoS2 coatings results in a more compact microstructure. The hardness of the coatings increases with the doping of V. The MoS2-V coating deposited at a current of 0.2 A obtains the lowest friction coefficient (0.043) under vacuum. As the amount of V doping increases, the wear rate of the coating decreases first and then increases, among which the coating deposited at a current of 0.5 A has the lowest wear rate of 2.2 × 10–6 mm3/N·m.

Originality/value
This work elucidates the role of V doping on the lubrication mechanism of MoS2 coatings in a vacuum environment, and the MoS2-V coating is expected to be applied as a solid lubricant in space environment.