bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal activation affects the organization and protein composition of the nuclear speckles
Authors: Szczepankiewicz Andrzej Antoni , Parobczak Kamil , Zaręba-Kozioł Monika , Ruszczycki Błażej , Bijata Monika , Trzaskoma Paweł , Hajnowski Grzegorz , Holm-Kaczmarek Dagmara , Włodarczyk Jakub , Wilczyński Grzegorz Marek , Rędowicz Maria Jolanta , Magalska Adriana
Published: March 2024

Nuclear speckles, also known as interchromatin granule clusters (IGCs), are subnuclear domains highly enriched in proteins involved in transcription and mRNA metabolism and, until recently, have been regarded primarily as their storage and modification hubs. However, several recent studies on non-neuronal cell types indicate that nuclear speckles may directly contribute to gene expression as some of the active genes have been shown to associate with these structures.

Neuronal activity is one of the key transcriptional regulators and may lead to the rearrangement of some nuclear bodies. Notably, the impact of neuronal activation on IGC/nuclear speckles organization and function remains unexplored. To address this research gap, we examined whether and how neuronal stimulation affects the organization of these bodies in granular neurons from the rat hippocampal formation. Our findings demonstrate that neuronal stimulation induces morphological and proteomic remodelling of the nuclear speckles under bothin vitroandin vivoconditions. Importantly, these changes are not associated with cellular stress or cell death but are dependent on transcription and splicing.
The lipid droplet protein DHRS3 is a regulator of melanoma cell state
Authors: Johns Eleanor , Ma Yilun , Louphrasitthipol Pakavarin , Peralta Christopher , Hunter Miranda V. , Raymond Jeremy H. , Molina Henrik , Goding Colin R. , White Richard M.
Published: March 2024

Lipid droplets are fat storage organelles composed of a protein envelope and lipid rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling.
The Effects of Acute Coordinative vs. Acute Endurance Exercise on the Cortisol Concentration
Authors: Budde Henning , Wegner Mirko , Ahrens Christiane , Velasques Bruna , Ribeiro Pedro , Machado Sergio , Gronwald Thomas , Amatriain-Fernández Sandra , Schaffarczyk Marcelle , Mueller-Alcazar Anett
Published: March 2024

Background

Physical exercise interventions can cause neuroendocrine activation, which in turn increases salivary cortisol concentrations. Until now there have been no studies comparing endurance and coordinative exercise.

Objective

The purpose of this study was to examine the effects of these different interventions with an intraindividual comparison.

Methods

61 students between 18 and 30 years of age were included and first completed a coordinative exercise and one week later an endurance exercise of the same intensity and length which was self-set on the first day, with a maximum heart rate of 64 - 76% (HRmax) over a period of 15 min. To measure changes in the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, saliva samples were collected before (t1) and after exercise (t2 and t3).

Results

Baseline values of cortisol (t0) did not differ significantly between coordinative and endurance exercise, t(55) = .233,p= .816. Post hoc tests revealed that the cortisol values of the second coordinative vs. endurance time point,t(55) = 2.097,p= .040,d= .741, and third coordinative vs. endurance time point,t(55) = 3.004,p= .004,d= .735, differed significantly with large effect sizes.

Conclusion

The results show for the first time that coordinative exercise produced a higher cortisol release than endurance exercise of the same intensity and duration. Interventions such as coordinative exercise require higher cognitive components resulting in stronger cortisol release than endurance exercise. Thus, the type of acute exercise is a psychophysiological factor in determining the neuroendocrine stress response.

Key points

Cortisol is an important catabolic hormone when it comes to overtraining or burnout in an athlete. Our results show for the first time that acute coordinative exercise produces a higher cortisol release than endurance exercise of the same intensity and duration.
Does behavior mediate the effect of weather on SARS-CoV-2 transmission? Evidence from cell-phone data
Authors: Grover Elise N. , Buchwald Andrea G. , Ghosh Debashis , Carlton Elizabeth J.
Published: March 2024

Background

There is growing evidence that weather alters SARS-CoV-2 transmission, but it remains unclear what drives the phenomenon. One prevailing hypothesis is that people spend more time indoors in cooler weather, leading to increased spread of SARS-CoV-2 related to time spent in confined spaces and close contact with others. However, the evidence in support of that hypothesis is limited and, at times, conflicting.

Objectives

We aim to evaluate the extent to which weather impacts COVID-19 via time spent away-from-home in indoor spaces, as compared to a direct effect of weather on COVID-19 hospitalization, independent of mobility.

Methods

We use a mediation framework, and combine daily weather, COVID-19 hospital surveillance, cellphone-based mobility data and building footprints to estimate the relationship between daily indoor and outdoor weather conditions, mobility, and COVID-19 hospitalizations. We quantify the direct health impacts of weather on COVID-19 hospitalizations and the indirect effects of weather via time spent indoors away-from-home on COVID-19 hospitalizations within five Colorado counties between March 4th2020 and January 31st2021.

Results

We found evidence that changes in 12-day lagged hospital admissions were primarily via the direct effects of weather conditions, rather than via indirect effects by which weather changes time spent indoors away-from-home. Sensitivity analyses evaluating time at home as a mediator were consistent with these conclusions.

Discussion

Our findings do not support the hypothesis that weather impacted SARS-CoV-2 transmission via changes in mobility patterns during the first year of the pandemic. Rather, weather appears to have impacted SARS-CoV-2 transmission primarily via mechanisms other than human movement. We recommend further analysis of this phenomenon to determine whether these findings generalize to current SARS-CoV-2 transmission dynamics and other seasonal respiratory pathogens.
Optimal Pair Matching Combined with Machine Learning Predicts that Omega-3 Fatty Acid Supplementation Markedly Reduces the Risk of Myocardial Infarction in African Americans
Authors: Sun Shudong , Hara Aki , Johnstone Laurel , Hallmark Brian , Lu Eric , Watkins Joseph C. , Thomson Cynthia A. , Schembre Susan M. , Sergeant Susan , Umans Jason , Yao Guang , Zhang Hao Helen , Chilton Floyd H.
Published: March 2024

Conflicting results from clinical trials have contributed to a lack of consensus about cardioprotective effects of omega-3 (n-3) highly unsaturated fatty acids (HUFA). Although the VITAL trial did not demonstrate an overall benefit of n-3 HUFA supplementation on composite cardiovascular disease (CVD) and cancer outcomes, the substantial enrollment of African Americans (AfAm) afforded a unique opportunity for a post-hoc analysis of racial differences in the supplementation response. We employed propensity score matching to address potential covariate imbalances between AfAm and European American (EuAm) participants in VITAL (N=3,766 participants). Using Kaplan-Meier curves and two machine learning methodologies, we found that n-3 HUFA supplementation was significantly associated with a reduced risk of myocardial infarction (MI) exclusively in the AfAm subgroup, as evidenced by an odds ratio of 0.17 (95% CI [0.048, 0.59]). These findings indicate a potential cardioprotective benefit of n-3 supplementation in AfAm, specifically in reducing MI risks; a risk not identified in EuAm. Further investigation of n-3 HUFA effects through a hypothesis-driven randomized clinical trial among AfAm is needed to test a race-specific response that may inform recommendations for n-3 HUFA supplementation.
FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis
Authors: Hugener Jannik , Xu Jingwei , Wettstein Rahel , Ioannidi Lydia , Velikov Daniel , Wollweber Florian , Henggeler Adrian , Matos Joao , Pilhofer Martin
Published: March 2024

Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a “Filament IDentification” (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of gently lysed cells. FilamentID identified the mitochondrial filaments as the conserved aldehyde dehydrogenase Ald4ALDH2and the nucleoplasmic/cytoplasmic filaments being composed of acetyl-CoA synthetase Acs1ACSS2. The near-native high-resolution structures revealed the mechanism underlying polymerization and enabled us to perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores, and more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.

HIGHLIGHTS

FilamentID: a multiscale imaging workflow to characterize cellular filaments of unknown composition

The conserved aldehyde dehydrogenase Ald4ALDH2polymerizes into filament arrays within meiotic mitochondria

The conserved acetyl-CoA synthetase Acs1ACSS2forms filament arrays in the nucleus and the cytoplasm

Metabolites mediate Acs1 polymerization to store Acs1 in an inactive state in gametes and starved cells

Acs1 filament formation is required for efficient return to growth from starvation stress
A Systems Biology Analysis of Chronic Lymphocytic Leukemia
Authors: Pozzati Giulia , Zhou Jinrui , Hazan Hananel , Klement Giannoula Lakka , Siegelmann Hava T. , Rietman Edward A. , Tuszynski Jack A.
Published: March 2024

Whole-genome sequencing has revealed that TP53, NOTCH1, ATM, SF3B1, BIRC3, ABL, NXF1, BCR, ZAP70 are often mutated in CLL, but not consistently across all CLL patients. This paper employs a statistical thermo-dynamics approach in combination with the systems biology of the CLL protein-protein interaction networks to identify the most significant participant proteins in the cancerous transformation. Betti number (a topology of complexity) estimates highlight a protein hierarchy, primarily in the Wnt pathway known for aberrant CLL activation. These individually identified proteins suggest a network-targeted strategy over single-target drug development. The findings advocate for a multi-target inhibition approach, limited to several key proteins to minimize side effects, thereby providing a foundation for designing therapies. This study emphasizes a shift towards a comprehensive, multi-scale analysis to enhance personalized treatment strategies for CLL, which could be experimentally validated using siRNA or small molecule inhibitors. The result is not just the identification of these proteins but their rank-order, offering a potent signal amplification in the context of the 20,000 proteins produced by the human body, thus providing a strategic basis for therapeutic intervention in CLL, underscoring the necessity for a more holistic, cellular, chromosomal, and genome-wide study to develop tailored treatments for CLL patients.

Author Summary

Chronic Lymphocytic Leukemia (CLL) is a unique and slowly progressing cancer affecting white blood cells, and research on CLL has highlighted the inconsistency of gene mutations across patients. Using a novel approach that merges statistical thermodynamics and systems biology, this research examines the CLL protein-protein interaction networks to pinpoint proteins integral to the onset of the disease. Betti number (a topology of complexity) estimates, which measure the importance of individual proteins when removed from the network, helped identify numerous potential therapeutic targets, notably within the Wnt signaling pathway, a pathway implicated in various cellular processes and known for its defective expression in CLL. The finding advocates for a multi-target inhibition approach, focusing on several key proteins to minimize side effects, thereby laying a foundation for designing more effective therapies for CLL. This paper emphasizes the potential benefits of a comprehensive study, spanning cellular to genome-wide scales, to design personalized treatments for CLL patients.
Proteome analysis provides insights into sex differences inHolothuria Scabra
Authors: Cheng Chuhang , Wu FeiFei , Xu Yizhi , Ren Chunhua , Chen Ting , Li Shella , Shen Peihong , Jiang Fajun
Published: March 2024

Sex-determining mechanism is still ambiguous for sea cucumberHolothuria scabrawhich only manifests gonochorism in gonad. In this study, proteomic analysis was employed to delineate sex-related proteins and genes in gonads ofH. scabra, subsequently validated through Quantitative real-time polymerase chain reaction (qRT-PCR). A total of 5,313 proteins were identified via proteome sequencing. Among these, 817 proteins exhibited expression in both the ovary and testis, with 445 proteins displaying up-regulation and 372 proteins showing down-regulation. Furthermore, 136 and 69 proteins were identified as ovary-specific and testis-specific Differentially Abundant Proteins (DAPs), respectively. For the validation of 75 DAP coding genes, 9 genes were considered to be reliable. Notably, 25 ovary-bias proteins enriched in ribosome pathway strongly indicated the crucial role of ribosome in ovary. And 5S/18S rRNA ratio inH. Scabramay have potencial to establish a nondestructive method to distinguish sexes unambiguously. This study serves to furnish novel evidence pertaining to sex differences inH. scabra.
Intron-lariat spliceosomes convert lariats to true circles: implications for intron transposition
Authors: Ares Manuel , Igel Haller , Katzman Sol , Donohue John P.
Published: March 2024

Rare, full length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envision and test a hypothesis for their formation usingSaccharomyces cerevisiae, documenting full length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron-lariat spliceosome (ILS) in which the 3’-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3’ processing machinery) attacks the branch, joining the intron 3’ end to the 5’ splice site in a 3’-5’ linked circle. Human U2 and U12 spliceosomes produce analogous full length and processed circles. Post-splicing catalytic activity of the spliceosome may promote intron transposition during eukaryotic genome evolution.
The magnitude of exercise-induced hypoalgesia can be improved and correlated with endogenous pain modulation following 4 weeks of treadmill running
Authors: Xu Zi-Han , An Nan , Xu Shuang , Wang Ru-Yun , Li Yue
Published: March 2024

Objective

We aimed to investigate changes in pain perception, acute exercise-induced hypoalgesia (EIH), and endogenous pain modulation responses following 4-week treadmill running exercises of different intensities in healthy individuals.

Methods

Fifty-six healthy individuals included in this study. All participants were randomly assigned to three experimental groups (TRH, high intensity running, TRM, moderate intensity running and TRL, low intensity running). All participants performed 12 treadmill running sessions within 4 weeks at different intensities based on their target heart rate (THR). A running assessment was administered one week before running sessions. The magnitudes of EIH, conditioned pain modulation (CPM), and temporal summation (TS) responses following regular treadmill running were assessed. Pressure pain thresholds (PPT) or mechanical pain thresholds (MPT) were also determined following regular treadmill running.

Results

Treadmill running only induced acute EIH responses, with all pre-running PPT and MPT remaining unaltered. The acute EIH following each running sessions and CPM responses were also significantly improved in both the TRM and TRL groups, with TS score decreased in the TRM group.

Conclusions

A 4-week low to moderate intensity treadmill running improved acute EIH response by enhancing endogenous pain modulation in healthy individuals. Future studies should consider sex, behavior, and physiological factors to provide a comprehensive understanding of the changes in EIH following regular exercises.
A Multiple Session Dataset of NIRS Recordings From Stroke Patients Controlling Brain–Computer Interface
Authors: Isaev Mikhail R. , Mokienko Olesya A. , Lyukmanov Roman Kh. , Ikonnikova Ekaterina S. , Cherkasova Anastasiya N. , Suponeva Nataliya A. , Piradov Michael A. , Bobrov Pavel D.
Published: March 2024

This paper presents an open dataset of over 50 hours of near infrared spectroscopy (NIRS) recordings. Fifteen stroke patients completed a total of 237 motor imagery brain–computer interface (BCI) sessions. The BCI was controlled by imagined hand movements; visual feedback was presented based on the real– time data classification results. We provide the experimental records, patient demographic profiles, clinical scores (including ARAT and Fugl–Meyer), online BCI performance, and a simple analysis of hemodynamic response. We assume that this dataset can be useful for evaluating the effectiveness of various near– infrared spectroscopy signal processing and analysis techniques in patients with cerebrovascular accidents.
Epigenetic Reprogramming Mediates Monocyte and Heterologous T Cell-derived Cytokine Responses after BCG Vaccination
Authors: Qi Cancan , Liu Zhaoli , Kilic Gizem , Sarlea Andrei S. , Debisarun Priya A. , Liu Xuan , Mekonnen Yonatan Ayalew , Li Wenchao , Grasshoff Martin , Alaswad Ahmed , Petkoglou Apostolos , Koeken Valerie A.C.M. , Moorlag Simone J.C.F.M. , J. de Bree L. Charlotte , Mourits Vera P. , Joosten Leo A.B. , Li Yang , Netea Mihai G. , Xu Cheng-Jian
Published: March 2024

Epigenetic reprogramming plays an important role in shaping immune memory traits within both innate (trained immunity) and adaptive immune cells following Bacillus Calmette-Guérin (BCG) vaccination. However, the precise impact of dynamic DNA methylation alterations on immunological responses after BCG vaccination remains inadequately elucidated. To address this knowledge gap, we conducted a comprehensive study by integrating longitudinal analysis and systems biology approaches. We established a cohort of 284 healthy Dutch individuals, capturing data on genetics, cytokine responses toex vivostimulation and genome-wide DNA methylation at baseline, as well as at 14 days and 90 days after BCG vaccination. Our findings revealed distinct patterns of DNA methylation alternations in the short- and long-term following BCG vaccination. Moreover, we established that baseline DNA methylation profiles exert influence on the change in interferon-γ (IFN-γ) production upon heterologous (Staphylococcus aureus)stimulation before and after BCG vaccination. Specifically, we identified the regulation of kisspeptin as a novel pathway implicated in the modulation of IFN-γ production, and this finding has been substantiated through experiment validation. We also observed associations between BCG-induced DNA methylation changes and increased IFN-γ and Interleukin-1 β (IL-1β) production uponS. aureusstimulation. Interestingly, by integrating with genetic, epigenetic, and cytokine response data from the same individuals, mediation analysis demonstrated that most of the identified DNA methylation changes played a mediating role between genetic variants and cytokine responses, for example, the changes of cg21375332 nearSLC12A3gene mediated the regulation of genetic variants on IFN-γ changes after BCG vaccination. Sex-specific effects consistently manifested in DNA methylation changes after BCG vaccination and in the association between baseline methylation and cytokine responses. Together, our findings provide deeper insights into immune response mechanisms, crucial for developing effective epigenetic-based medical interventions for personalized medicine.
Applying Deep Learning in Heart Failure: Hospital Readmission is Not Like Other Health Quality Metrics
Authors: Shepherd Hailey M. , Heaton Jeffrey T. , Marghitu Theodore , Bai Yun Z. , Subramanian Melanie P. , Roberts Sophia H. , McGilvray Martha M.O. , Pawale Amit A. , Ewald Gregory A. , Cupps Brian P. , Pasque Michael K. , Foraker Randi E.
Published: March 2024

Background

Early identification of heart failure patients at increased risk for near-term adverse outcomes would assist clinicians in efficient resource allocation and improved care. Deep learning can improve identification of these patients.

Methods

This retrospective study examined adult heart failure patients admitted to a tertiary care institution between January 2009 and December 2018. A deep learning model was constructed with a dense input layer, three long short-term memory (LSTM) layers, and a dense hidden layer to cohesively extract features from time-series and non-time-series EHR data. Primary outcomes were all-cause hospital readmission or death within 30 days after hospital discharge.

Results

Among a final subset of 49,675 heart failure patients, we identified 171,563 hospital admissions described by 330 million EHR data points. There were 22,111 (13%) admissions followed by adverse 30-day outcomes, including 19,122 readmissions (87%) and mortality in 3,330 patients (15%). Our final deep learning model achieved an area under the receiver-operator characteristic curve (AUC) of 0.613 and precision-recall (PR) AUC of 0.38.

Conclusions

This EHR-based deep learning model developed from a decade of heart failure care achieved marginal clinical accuracy in predicting very early hospital readmission or death despite previous accurate prediction of 1-year mortality in this large study cohort. These findings suggest that factors unavailable in standard EHR data play pivotal roles in influencing early hospital readmission.

Clinical Perspective

What is new?

We developed an EHR-based deep learning model trained by 330 million data points from one of the largest cohorts of heart failure patients to date. Despite this model’s highly accurate prediction of long-term outcomes, such as mortality and disease progression, our findings suggest that EHR data alone offers limited predictive power for predicting the short-term outcomes of 30-day hospital readmission or death.

What are the clinical implications?

Our study supports the notion that hospital readmission, in contrast to other health outcomes, is uniquely driven by additional factors beyond traditional EHR variables. Once identified, incorporation of these determinants into future deep learning models could allow for accurate heart failure risk-stratification at hospital discharge to facilitate more efficient allocation of limited resources to the most vulnerable patients.
Hypercholesterolemia-induced impairment in sorafenib functionality is overcome by avasimibe co-treatment
Authors: Athavale Dipti , Yaduvanshi Himanshi , Bhati Firoz Khan , Mayengbam Shyamananda Singh , More Tushar , Rapole Srikanth , Bhat Manoj Kumar
Published: March 2024

Avasimibe; a cholesterol-lowering drug with a proven safety in clinical trials, has recently been repositioned as an anticancer agent in various preclinical investigations. A study from our group reported that hypercholesterolemia promotes hepatocellular carcinoma (HCC) cell survival and hampers the anticancer effect of sorafenib, a kinase inhibitor. In the present study, we demonstrate that in HCC under hypercholesterolemic conditions the anticancer property of sorafenib is potentiated by avasimibe (AVA) co-treatment. Further, to elucidate the role of hypercholesterolemia on sorafenib efficacy,in vitroandin vivomodels of HCC were used.In vitro, co-treatment of both drugs synergistically inhibited HCC cell viability and induced cell death under normal and hypercholesterolemic conditions. At the molecular level, downregulation of ERK signalling and induction of endoplasmic reticulum stress are likely to contribute to the combinatorial cytotoxic effect of sorafenib and avasimibein vitro. In mice, fed on a high-cholesterol diet (HCD), the efficacy of sorafenib was restored by co-administration of AVA. Collectively, these findings suggest that impairment in the efficacy of sorafenib because of hypercholesterolemic phenotype could be restored by AVA co-treatment, which may have implications towards treatment strategy.

Highlights

Cholesterol impedes sorafenib efficacy in Hepatocellular carcinoma cells.

Avasimibe restores the functionality of sorafenib under hypercholesterolemic environment.

Combine treatment of sorafenib and avasimibe synergistically enhances cytotoxicity in hepatocellular carcinoma.

Sorafenib and avasimibe treatment in the presence of LDLc.is associated with diminished ERK activation and increased ER stress.
Bidirectional modulation of reward-guided decision making by dopamine
Authors: Dias Maile Ana Antonia , Gründler Theo OJ , Froböse Monja I , Kurtenbach Hannah , Kaiser Luca F , Jocham Gerhard
Published: March 2024

The neuromodulator dopamine is known to play a key role in reward-guided decision making, where choice options are often characterized by multiple attributes. Different decision strategies can be used to merge these choice attributes with personal preferences (e.g. risk preferences) and integrate them into a single subjective value. While the influence of dopamine on risk preferences has been investigated, it is unknown whether dopamine is also involved in arbitrating between decision strategies. We investigated this using a reward-guided decision-making task which was performed by 31 healthy participants under the influence of the dopamine D2/D3-receptor antagonist amisulpride, the dopamine precursor L-DOPA, or placebo in a double-blind within-subject design. Notably, we observed that the dopaminergic interventions shifted the (overall) weighting of option attributes without changing how option attributes are integrated into a subjective value (decision strategy). These effects were bidirectional: Amisulpride reduced the degree to which choices were influenced by both reward magnitude and reward probability, whereas the opposite was observed under L-DOPA, where we found an increased effect of reward magnitude and reward probability on choice. These effects occurred in the absence of changes in statistically optimal behavior. Together, our data provide evidence for a role of dopamine in controlling the influence of value parameters on choice irrespective of decision strategies.
Global variation in prior exposure shapes antibody neutralization profiles of SARS-CoV-2 variants up to BA.2.86
Authors: Turner Sam , Amirthalingam Gayatri , Bailey Dalan , Barouch Dan H. , Bewley Kevin R. , Brown Kevin , Cao Yunlong , Chan Yung-Wai , Charlton Sue ,   DOVE consortium, Coombes Naomi S. , Hallis Bassam , Ho David D. , Jian Fanchong , Lasrado Ninaad , Lassaunière Ria , Liu Lihong , Montefiori David C. , Moss Paul , Newman Joseph , Parry Helen , Polacek Charlotta , Rasmussen Morten , Shao Fei , Shen Xiaoying , Thakur Nazia , Thomson Emma C. , Wang Jing , Wang Peng , Wang Qian , Willett Brian J. , Yisimayi Ayijiang , Smith Derek J.
Published: March 2024

The highly mutated SARS-CoV-2 variant, BA.2.86, and its descendants are now the most frequently sequenced variants of SARS-CoV-2. We analyze antibody neutralization data from eight laboratories from the UK, USA, Denmark, and China, including two datasets assessing the effect of XBB.1.5 vaccines, to determine the effect of infection and vaccination history on neutralization of variants up to and including BA.2.86, and produce antibody landscapes to describe these neutralization profiles. We find evidence for lower levels of immune imprinting on pre-Omicron variants in sera collected from Denmark and China, which may be explained by lower levels of circulation of the ancestral variant in these countries, and the use of an inactivated virus vaccine in China.
Molecular dynamics unveils multiple-site binding of inhibitors with reduced activity on the surface of dihydrofolate reductase
Authors: Araki Mitsugu , Ekimoto Toru , Takemura Kazuhiro , Matsumoto Shigeyuki , Tamura Yunoshin , Kokubo Hironori , Bekker Gert-Jan , Yamane Tsutomu , Isaka Yuta , Sagae Yukari , Kamiya Narutoshi , Ikeguchi Mitsunori , Okuno Yasushi
Published: March 2024

The sensitivity to protein inhibitors is altered by modifications or protein mutations, as represented by drug resistance. The mode of stable drug binding to the protein pocket has been experimentally clarified. However, the nature of the binding of inhibitors with reduced sensitivity remains unclear at the atomic level. In this study, we analyzed the thermodynamics and kinetics of inhibitor binding to the surface of wild-type and mutant dihydrofolate reductase (DHFR) using molecular dynamics simulations combined with Markov state modeling. A strong inhibitor of methotrexate (MTX) showed a preference for the active site of wild-type DHFR with minimal binding to unrelated (secondary) sites. Deletion of a side-chain fragment in MTX largely destabilized the active site-bound state, with clear evidence of binding to secondary sites. Similarly, the F31V mutation in DHFR diminished the specificity of MTX binding to the active site. These results reveal the presence of multiple-bound states whose stabilities are comparable to or higher than those of the unbound state, suggesting that a reduction in the binding affinity for the active site significantly elevates the fractions of these states. This study sheds light on the specific drug recognition by proteins and the selectivity of drug binding sites on protein surfaces. (199 words)
Transcript-specific enrichment enables profiling rare cell states via scRNA-seq
Authors: Abay Tsion , Stickels Robert R. , Takizawa Meril T. , Nalbant Benan N. , Hsieh Yu-Hsin , Hwang Sidney , Snopkowski Catherine , Yu Kenny Kwok Hei , Abou-Mrad Zaki , Tabar Viviane , Ludwig Leif S. , Chaligné Ronan , Satpathy Ansuman T. , Lareau Caleb A.
Published: March 2024

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing (scRNA-seq) identifies many rare populations of interest that express specific marker transcript combinations, traditional flow sorting limits our ability to enrich these populations for further profiling, including requiring cell surface markers with high-fidelity antibodies. Additionally, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers. To address these limitations, we describe Programmable Enrichment via RNA Flow-FISH by sequencing (PERFF-seq), a scalable assay that enables scRNA-seq profiling of subpopulations from complex cellular mixtures defined by the presence or absence of specific RNA transcripts. Across immune populations (n= 141,227 cells) and fresh-frozen and formalin-fixed paraffin-embedded brain tissue (n= 29,522 nuclei), we demonstrate the sorting logic that can be used to enrich for cell populations via RNA-based cytometry followed by high-throughput scRNA-seq. Our approach provides a rational, programmable method for studying rare populations identified by one or more marker transcripts.
Restricted quantum focusing
Authors: Shahbazi-Moghaddam Arvin
Published: March 2024

Quantum focusing is a powerful conjecture that plays a key role in the current proofs of many well-known quantum gravity theorems, including various consistency conditions, and causality constraints in AdS/CFT. We conjecture a (weaker) quantum focusing, which we argue is sufficient to derive all known essential implications of quantum focusing. Subject to a technical assumption, we prove this conjecture in braneworld semiclassical gravity theories that are holographically dual to Einstein gravity in a higher-dimensional anti–de Sitter spacetime.

Published by the American Physical Society
2024
Cascades of Parametric Instabilities in the Tokamak Plasma Edge during Electron Cyclotron Resonance Heating
Authors: Clod A. , Senstius M. G. , Nielsen A. H. , Ragona R. , Thrysøe A. S. , Kumar U. , Coda S. , Nielsen S. K. ,   The TCV team
Published: March 2024

We report observations of nonlinear two-plasmon decay instabilities (TPDIs) of a high-power microwave beam, a process similar to half-harmonic generation in optics, during electron cyclotron resonance heating in a tokamak. TPDIs are found to occur regularly in the plasma edge due to wave trapping in density fluctuations for various confinement modes, and the frequencies of both observed daughter waves agree with modeling. Emissions from a cascade of subsequent decays, which indicate a generation of ion Bernstein waves, are correlated with fast-ion generation. This emphasizes the limitations of standard linear microwave propagation models and possibly paves the way for novel microwave applications in plasmas.

Published by the American Physical Society
2024
Bis[2,6-bis(1H-benzimidazol-2-yl)pyridine]ruthenium(II) bis(hexafluoridophosphate) diethyl ether trisolvate
Authors: Althubyani Layla M. , MacLean Brian J. , Robertson Katherine N. , Aquino Manuel A.S.
Published: March 2024

The title compound, [Ru(C19H13N5)2](PF6)2·3C4H10O, was obtained from the reaction of Ru(bimpy)Cl3 [bimpy is 2,6-bis(1H-benzimidazol-2-yl)pyridine] and bimpy in refluxing ethanol followed by recrystallization from diethyl ether/acetonitrile. At 125 K the complex has orthorhombic (Pca21) symmetry. It is remarkable that the structure is almost centrosymmetric. However, refinement in space group Pbcn leads to disorder and definitely worse results. It is of interest with respect to potential catalytic reduction of CO2. The structure displays N—H...O, N—H...F hydrogen bonding and significant π–π stacking and C—H...π stacking interactions.
Addiction recovery stories: Ceri Pimblett in conversation with Lisa Ogilvie
Authors: Pimblett Ceri , Ogilvie Lisa
Published: March 2024

Purpose

The purpose of this paper is to examine recovery through lived experience. It is part of a series that explores candid accounts of addiction and recovery to identify important components in the recovery process.

Design/methodology/approach

The G-CHIME model comprises six elements important to addiction recovery (growth, connectedness, hope, identity, meaning in life and empowerment). It provides a standard against which to consider addiction recovery, having been used in this series, as well as in the design of interventions that improve well-being and strengthen recovery. In this paper, a first-hand account is presented, followed by a semi-structured e-interview with the author of the account. Narrative analysis is used to explore the account and interview through the G-CHIME model.

Findings

This paper shows that addiction recovery is a remarkable process that can be effectively explained using the G-CHIME model. The significance of each component in the model is apparent from the account and e-interview presented.

Originality/value

Each account of recovery in this series is unique and, as yet, untold.
Global fast terminal sliding mode control for automatic carrier landing with environmental disturbances
Authors: Yao Zhuoer , Kan Zi , Li Daochun , Shao Haoyuan , Xiang Jinwu
Published: March 2024

Purpose

The purpose of this paper is to solve the challenging problem of automatic carrier landing with the presence of environmental disturbances. Therefore, a global fast terminal sliding mode control (GFTSMC) method is proposed for automatic carrier landing system (ACLS) to achieve safe carrier landing control.

Design/methodology/approach

First, the framework of ACLS is established, which includes flight glide path model, guidance model, approach power compensation system and flight controller model. Subsequently, the carrier deck motion model and carrier air-wake model are presented to simulate the environmental disturbances. Then, the detailed design steps of GFTSMC are provided. The stability analysis of the controller is proved by Lyapunov theorems and LaSalle’s invariance principle. Furthermore, the arrival time analysis is carried out, which proves the controller has fixed time convergence ability.

Findings

The numerical simulations are conducted. The simulation results reveal that the proposed method can guarantee a finite convergence time and safe carrier landing under various conditions. And the superiority of the proposed method is further demonstrated by comparative simulations and Monte Carlo tests.

Originality/value

The GFTSMC method proposed in this paper can achieve precise and safe carrier landing with environmental disturbances, which has important referential significance to the improvement of ACLS controller designs.
Explicating the mapping between big data and knowledge management: a systematic literature review and future directions
Authors: Goswami Anil Kumar , Sinha Anamika , Goswami Meghna , Kumar Prashant
Published: March 2024

Purpose

This study aims to extend and explore patterns and trends of research in the linkage of big data and knowledge management (KM) by identifying growth in terms of numbers of papers and current and emerging themes and to propose areas of future research.

Design/methodology/approach

The study was conducted by systematically extracting, analysing and synthesizing the literature related to linkage between big data and KM published in top-tier journals in Web of Science (WOS) and Scopus databases by exploiting bibliometric techniques along with theory, context, characteristics, methodology (TCCM) analysis.

Findings

The study unfolds four major themes of linkage between big data and KM research, namely (1) conceptual understanding of big data as an enabler for KM, (2) big data–based models and frameworks for KM, (3) big data as a predictor variable in KM context and (4) big data applications and capabilities. It also highlights TCCM of big data and KM research through which it integrates a few previously reported themes and suggests some new themes.

Research limitations/implications

This study extends advances in the previous reviews by adding a new time line, identifying new themes and helping in the understanding of complex and emerging field of linkage between big data and KM. The study outlines a holistic view of the research area and suggests future directions for flourishing in this research area.

Practical implications

This study highlights the role of big data in KM context resulting in enhancement of organizational performance and efficiency. A summary of existing literature and future avenues in this direction will help, guide and motivate managers to think beyond traditional data and incorporate big data into organizational knowledge infrastructure in order to get competitive advantage.

Originality/value

To the best of authors’ knowledge, the present study is the first study to go deeper into understanding of big data and KM research using bibliometric and TCCM analysis and thus adds a new theoretical perspective to existing literature.
Unpacking the sociomaterial parameters of connectivity management practices in the Saudi academic context
Authors: Aljabr Njod , Petrakaki Dimitra , Chamakiotis Petros
Published: March 2024

Purpose

Existing research on how professionals manage after-hours connectivity to work has been dominated by studies on the strategies/practices individuals develop. In these studies, mobile technology is perceived as a tool or an enabler that supports otherwise human-centric connectivity decisions. This view sees technology as separate or external to the organisation, missing out on its nuanced role in shaping connectivity decisions. Our study aims to bring technology back into the sociomaterially imbricated context of connectivity and to unpack its parameters.

Design/methodology/approach

Drawing on data collected from documents and semi-structured interviews, we adopt the framework of “sociomaterial imbrications” (Leonardi, 2011) to understand the social and material parameters that influence connectivity management practices at two different academic institutions in Saudi Arabia.

Findings

The study identifies a set of social and material parameters (organisational, individual, technological and situational) that imbricate to shape, collectively and not individually, professionals’ connectivity management practices. Connectivity decisions to change practice (such as decisions of where, when or why to connect) or technology (how to connect) are not as distinct as they appear but originate from, and are founded on, imbricated sociomaterial parameters. Our study further suggests that connectivity decisions are shaped by individuals’ perceptions of sociomaterial imbrications, but decisions are not solely idiosyncratic. The context within which connectivity decisions are taken influences the type of decisions made.

Originality/value

Connectivity management emerged from sociomaterial imbrications within a context constitutive of four interacting parameters: organisational, technological, situational and individual. Decisions around the “how” and the “what” of connectivity – i.e. the practice of connectivity and its underpinning technology – originate from how people perceive sociomaterial imbrications as enabling or constraining within a context. Individual perceptions account for changes in practice and in technology, but the context they find themselves in is also important. For instance, we show that professionals may perceive a certain technology as affording, but eventually they may use another technology for communications due to social norms.
The effect of green intellectual capital and innovative work behavior on green process innovation performance in the hospitality industry
Authors: Shahbaz Muhammad Hamid , Naseem Muhammad Akram , Battisti Enrico , Alfiero Simona
Published: March 2024

Purpose

This study examines the direct and indirect effects of green intellectual capital (GIC) and innovative work behavior (IWB) on green process innovation performance (GPIP), with green knowledge sharing (GKS) as a mediator, in Pakistan’s hospitality industry. The aim is to provide a paradigm for assisting companies in transforming strategic green processes of green hotel innovation and its practices.

Design/methodology/approach

A total of 203 questionnaires were administered to front-desk officers of 15 hotels in Pakistan. Smart PLS-SEM 4 was used for analysis, and demographic statistics were analyzed using SPSS 21.0.

Findings

GIC (green human capital, green organizational capital and green relational capital) and IWB significantly and positively influence GPIP. GKS strengthens the relationships of GIC and IWB with GPIP. Finally, all hypotheses were significant and the constructs showed a positive association.

Originality/value

Research studies have revealed the impact of GIC on the hotel industry’s competitive advantage. However, the mechanisms underlying those impacts remain relatively underexplored. This study makes valuable contributions by providing crucial evidence from Pakistan’s hospitality industry.
The relation between donation motivations and the meaning in life
Authors: Sabah Şenay , Oflazoğlu Sonyel
Published: March 2024

Purpose

This paper aims to identify the primary motivations for clothing donations to the immediate social environment. Furthermore, a model that describes the relationship between these motivations, donation tendency and meaning in life is developed and tested.

Design/methodology/approach

A mixed method is applied. In the first study, interviews were conducted with 11 people determined with maximum diversity. With the factors that evolved in the first study, a survey method was applied in the second study, and 346 data were collected by convenience sampling.

Findings

Individual (independent and interdependent self-construals) and religious motivations for donating clothes to the immediate social surroundings emerge from the interview results. The second study focuses on the relationship between the concept of meaning in life and donation and the possible drivers of donation identified in the first study. A positive relationship was hypothesised between independent self-construal/ intrinsic religiosity/donation tendency and life meaning, as well as between interdependent self-construal and donation tendency. The research results validated all of the hypotheses. The relationship between independent self-construal/intrinsic religiosity and donating behaviour was statistically insignificant.

Originality/value

The current study's findings contain three features that support and enrich previous literature. The first thing is to identify the motivations for the donation tendency. The second issue is considering the meaning of life in terms of its motivations. The final point is to think about donating from a mixed-method perspective. This perspective, in particular, has the potential to provide a comprehensive understanding of the phenomena under discussion.