bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization, structure and inhibition of the human succinyl-CoA:glutarate-CoA transferase, a genetic modifier of glutaric aciduria type 1
Authors: Khamrui Susmita , Dodatko Tetyana , Wu Ruoxi , Leandro João , Sabovic Amanda , Violante Sara , Cross Justin R. , Marsan Eric , Kumar Kunal , DeVita Robert J. , Lazarus Michael B. , Houten Sander M.
Published: February 2024

Glutaric Aciduria Type 1 (GA1) is a serious inborn error of metabolism with no pharmacological treatments. A novel strategy to treat this disease is to divert the toxic biochemical intermediates to less toxic or non-toxic metabolites. Here, we report a novel target, SUGCT, which we hypothesize suppresses the GA1 metabolic phenotype through decreasing glutaryl-CoA. We report the structure of SUGCT, the first eukaryotic structure of a type III CoA transferase, develop a high-throughput enzyme assay and a cell-based assay, and identify valsartan and losartan carboxylic acid as inhibitors of the enzyme validating the screening approach. These results may form the basis for future development of new pharmacological intervention to treat GA1.
ASPYRE-Lung: Validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in tissue
Authors: Evans Ryan T , Gillon-Zhang Elizabeth , Brown Julia N. , Knudsen Katherine E. , King Candace , Green Amanda S , Silva Ana-Luisa , Mordaka Justyna M. , Palmer Rebecca N. , Tomassini Alessandro , Collazos Alejandra , Xyrafaki Christina , Turner Iyelola , Ho Chau Ha , Nugent Dilyara , Jose Jinsy , Andreazza Simonetta , von Bargen Kristine , Gray Eleanor R. , Stolarek-Januszkiewicz Magdalena , Cooke Aishling , Reddi Honey , Balmforth Barnaby W , Osborne Robert J
Published: February 2024

Genomic variant testing of tumors is a critical gateway for patients to access the full potential of personalized oncology therapeutics. Current methods such as next-generation sequencing are costly and challenging to interpret, while PCR assays are limited in the number of variants they can cover. We developed ASPYRE® (Allele-Specific PYrophosphorolysis REaction) technology to address the urgent need for rapid, accessible and affordable diagnostics informing actionable genomic target variants of a given cancer. The targeted ASPYRE-Lung panel for non-small cell carcinoma covers 114 variants in 11 genes (ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1, MET & NTRK1/2/3) to robustly inform clinical management. The assay detects single nucleotide variants, insertions, deletions, and gene fusions from tissue-derived DNA and RNA simultaneously. We tested the limit of detection, specificity, analytical accuracy and analytical precision of ASPYRE-Lung using FFPE lung tissue samples from patients with non-small cell lung carcinoma, variant-negative FFPE tissue from healthy donors, and FFPE-based contrived samples with controllable variant allele fractions. The sensitivity of ASPYRE-Lung was determined to be ≤ 3% variant allele fraction for single nucleotide variants and insertions or deletions, 100 copies for fusions, and 200 copies for MET exon 14 skipping. The specificity was 100% with no false positive results. The analytical accuracy test yielded no discordant calls between ASPYRE-Lung and expected results for clinical samples (via orthogonal testing) or contrived samples, and results were replicable across operators, reagent lots, runs, and real-time PCR instruments with a high degree of precision. The technology is simple and fast, requiring only four reagent transfer steps using standard laboratory equipment (PCR and qPCR instruments) with analysis via a cloud-based analysis algorithm. The ASPYRE-Lung assay has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with non-small cell carcinoma.
Huntingtin is an RNA-binding protein and participates in NEAT1-mediated paraspeckles
Authors: Yadav Manisha , Harding Rachel J. , Li Tiantian , Xu Xin , Gall-Duncan Terence , Khan Mahreen , Bardile Costanza Ferrari , Sequiera Glen L. , Duan Shili , Chandrasekaran Renu , Pan Anni , Bu Jiachuan , Yamazaki Tomohiro , Hirose Tetsuro , Prinos Panagiotis , Tippett Lynette , Turner Clinton , Curtis Maurice A. , Faull Richard L.M. , Pouladi Mahmoud A. , Pearson Christopher E. , He Housheng Hansen , Arrowsmith Cheryl H.
Published: February 2024

Abstract

Huntingtin protein, mutated in Huntington disease, is implicated in nucleic acid- mediated processes, yet evidence for direct huntingtin-nucleic acid interaction is limited. Here we show wildtype and mutant huntingtin co-purify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wildtype and mutant huntingtin revealed NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington’s disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin co-localized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a novel huntingtin interactor, demonstrating huntingtin’s involvement in RNA-mediated functions and paraspeckle regulation.

One-Sentence Summary

HTT is an RNA-binding protein that interacts with G-rich sequences, including those in the paraspeckle lncRNA NEAT1.
vmTracking: Virtual Markers Overcome Occlusion and Crowding in Multi-Animal Pose Tracking
Authors: Azechi Hirotsugu , Takahashi Susumu
Published: February 2024

In multi-animal tracking, addressing occlusion and crowding is crucial for accurate behavioral analysis. However, in situations where occlusion and crowding generate complex interactions, achieving accurate pose tracking remains challenging. Therefore, we introduced Virtual marker tracking (vmTracking), which uses virtual markers for individual identification. Virtual markers are labels derived from conventional markerless multi-animal tracking tools, such as multi-animal DeepLabCut (maDLC) and Social LEAP Estimate Animal Poses (SLEAP). Unlike physical markers, virtual markers exist only within the video and attribute features to individuals, enabling consistent identification throughout the entire video while keeping the animals markerless in reality. Using these markers as cues, annotations were applied to multi-animal videos, and tracking was conducted with single-animal DeepLabCut (saDLC) and SLEAP’s single-animal method. vmTracking minimized manual corrections and annotation frames needed for training, efficiently tackling occlusion and crowding. Experiments tracking multiple mice, fish, and human dancers confirmed vmTracking’s variability and applicability. These findings could enhance the precision and reliability of tracking methods used in the analysis of complex naturalistic and social behaviors in animals, providing a simpler yet more effective solution.
Lack of rhythmicity in Bmal1 deficient mice impairs motivation towards natural stimuli
Authors: Berbegal-Sáez Paula , Gallego-Landin Ines , Macía Javier , Alegre-Zurano Laia , Castro-Zavala Adriana , Welz Patrick-Simon , Benitah Salvador A , Valverde Olga
Published: February 2024

Maintaining appropriate circadian rhythmicity is essential for coordinating the activity of biological functions in mammalian organisms. A variety of physiological and behavioral changes have been associated with disturbances of this complex clock mechanism.

In the present study, we delve into the consequences of circadian arrhythmia using the Bmal1-knockout (KO) mouse line aiming to explore potential behavioral and motivational implications. We were able to identify the intricate activity patterns that define circadian disturbance in Bmal1-KO mice by utilizing a new analysis model based on entropy divergence.

Alterations in locomotor activity were accompanied by disruptions of circadian expression patterns in various clock genes as revealed by gene expression analysis. Additionally, we found a dysregulated gene expression profile in Bmal1-KO mice regarding genes related to circadian control in various brain nuclei. Specifically, the ventral striatum exhibited a dysregulation in the expression levels of genes modulating reward and motivation.

Further investigation revealed that BMAL1 deficient mice showed a sustained rise in motivation and seeking behavior for food and water reinforcers in the self-administration paradigm, independently of the caloric content of the reward. Together, our data reveal that disruptions in circadian rhythmicity, induced by alterations in the molecular clock, also impact the gene expression regulating the reward system. This, in turn, can lead to altered seeking behavior and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.
Adult neurogenesis through glial transdifferentiation in a CNS injury paradigm
Authors: Casas-Tintó Sergio , García-Guillen Nuria , Losada-Pérez Maria
Published: February 2024

As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other CNS injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience.

Glial cells support central nervous system (CNS) homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris, and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil associated glia (NG) inDrosophila, equivalent to vertebrate astrocytes, oligodendrocytes (OL) and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between ensheathing glia (EG) and astrocyte like glia (ALG). Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.
Synchronous Ensembles of Hippocampal CA1 Pyramidal Neurons Associated with Theta but not Ripple Oscillations During Novel Exploration
Authors: Chen En-Li , Chen Tsai-Wen , Schreiter Eric R. , Lin Bei-Jung
Published: February 2024

Synchronous neuronal ensembles play a pivotal role in the consolidation of long-term memory in the hippocampus. However, their organization during the acquisition of spatial memory remains less clear. In this study, we used neuronal population voltage imaging to investigate the synchronization patterns of CA1 pyramidal neuronal ensembles during the exploration of a new environment, a critical phase for spatial memory acquisition. We found synchronous ensembles comprising approximately 40% of CA1 pyramidal neurons, firing simultaneously in brief windows (∼25ms) during immobility and locomotion in novel exploration. Notably, these synchronous ensembles were not associated with contralateral ripple oscillations but were instead phase-locked to theta waves recorded in the contralateral CA1 region. Moreover, the subthreshold membrane potentials of neurons exhibited coherent intracellular theta oscillations with a depolarizing peak at the moment of synchrony. Among newly formed place cells, pairs with more robust synchronization during locomotion displayed more distinct place-specific activities. These findings underscore the role of synchronous ensembles in coordinating place cells of different place fields.
An auxin homeostat allows plant cells to establish and control defined transmembrane auxin gradients
Authors: Geisler Markus , Dreyer Ingo
Published: February 2024

Extracellular auxin maxima and minima are important to control plant developmental programs. Auxin gradients are provided by the concerted action of proteins from the three major plasma membrane auxin transporter classes AUX1/LAX, PIN and ABCB transporters. But neither genetic nor biochemical nor modelling approaches have been able to reliably assign the individual roles and interplay of these transporter types.

Based on the thermodynamic properties of the transporters, we show here by mathematical modeling and computational simulations that the concerted action of different auxin transporter types allow the adjustment of specific transmembrane auxin gradients. The dynamic flexibility of the “auxin homeostats” comes at the cost of an energy-consuming “auxin cycling” across the membrane.

An unexpected finding was that functional ABCB-PIN coupling appears to allow an optimization of the trade-off between the speed of auxin gradient adjustment on the one hand and ATP consumption and disturbance of general anion homeostasis on the other.

In conclusion, our analyses provide fundamental insights into the thermodynamic constraints and flexibility of transmembrane auxin transport in plants.

Plain language summary

The phytohormone auxin controls essentially plant development. Plant cells produce auxin and export it to establish patterns by local auxin minima and maxima. Although several transporter proteins are known to contribute to this process, the mechanism by which a defined auxin gradient can be produced is not clear. This study now uses mathematical modeling based on the thermodynamic features of the auxin transporters to illustrate in computational simulations the fundamental characteristics of an “auxin homeostat”. The concerted interplay of different auxin transporters allows plant cells to establish defined transmembrane auxin gradients that are the indispensable basis for polarized auxin maxima and minima and auxin fluxes within tissues.
Impact of a novel comprehensive empathy curriculum at Leicester Medical School: Protocol for a longitudinal study
Authors: Keshtkar Leila , Bennett-Weston Amber , Ward Andy , Winter Rachel , Gay Simon , Howick Jeremy
Published: February 2024

Background

Empathy appears to decline throughout medical school and is highly variable among qualified healthcare practitioners. To address these problems, the Leicester Medical School has designed an enhanced empathy curriculum that runs throughout all five years of medical school. The impact of this curriculum must be measured.

Objective

To evaluate the impact of the enhanced empathy curriculum using qualitative and quantitative data.

Study design

Prospective longitudinal study

Setting

Leicester medical school

Participants

All students (from year one to five) at the Leicester Medical School will be eligible for participation. There are currently approximately 300 students in each of the five years of medical school and we anticipate that we will recruit approximately 100 medical students per medical school year for the quantitative data (total of 500 students) and approximately 10 students per medical school year for the qualitative data (total of 50 students).

Data collection

We will annually collect the following data for a period of seven years to ensure a comprehensive dataset for three full cohorts of medical students. The main reason for selecting the seven-year timeframe is that the empathy curriculum recently started in medical school (2022-2023 academic year), and it takes a few years for it to stabilise and yield meaningful results.

Student empathy levels (for example, using the student version of the self-reported Jefferson Scale for Empathy (JSE-S) and the observer-reported Consultation and Relational Empathy (CARE) measure).

Satisfaction with the empathy curriculum (using routinely collected student survey data).

Satisfaction with the overall medical school curriculum (using routinely collected student survey data).

Student experiences of the empathy curriculum (using qualitative student interviews with a purposive sample of five to 10 medical students from each year).

Student well-being data (for example, the frequency and severity of well-being issues).

Reporting elements

We will report on:

Number of individuals at each stage of the study.

Descriptive data that includes (student characteristics and potential confounders).

Outcome data (empathy levels, student satisfaction with curriculum, student experience). We will also report on the relationships between these data (for example between empathy levels and student satisfaction with curriculum).

Dissemination

Findings will be disseminated through international conferences, news and peer-reviewed journals.

Funding

This study is funded by the Stoneygate Trust. The funder had no role in any part of the development or writing of this paper.

Ethics

The project and associated documents were approved by the University of Leicester Research Ethics Board (Ethical approval number: 42404-lk252-ls:medicine).
Compressive stress drives morphogenetic apoptosis through lateral tension and Piezo1
Authors: Merle Tatiana , Cazales Martine , Mangeat Thomas , Bouzignac Ronan , Ronsin Brice , Rouvière Christian , Suzanne Magali
Published: February 2024

Tissues and organs are constantly submitted to physical stress, including compression, stretching, shear stress. The impact of compression due to overcrowding on cell extrusion has been the focus of recent studies. However, how tissue compression impact cell death in the context of morphogenesis is mostly unexplored. Here, we showed that a natural compression is exerted on the Drosophila developing leg by the surrounding tissue (or envelope) that is required for correct leg morphogenesis. In this tissue, apoptosis, preferentially localized in the future fold region, contributes to drive tissue folding through the generation of a pulling force on the apical surface. However, only a subset of these cells are dying within the expression domain of proapoptotic genes and how this precise pattern of cell death is established is totally unknown. We found that the natural compression exerted by the envelope contributes to the regulation of apoptosis, revealing that compression constitutes an integral part of apoptosis regulation during leg morphogenesis. We further reveal that compression drives a significant increase in lateral tension and favors apoptosis through the mechanosensor Piezo. Finally, perturbing cell cortex anchoring or membrane stiffness prove sufficient to block this process. Altogether, these results open new perspectives in term of mechanotransduction during morphogenesis.
Dynamic Lateralization in Contralateral-Projecting Corticospinal Neurons During Motor Learning
Authors: Han Jiawei , Wang Ruixue , Wang Minmin , Yu Zhihua , Zhu Liang , Zhang Jianmin , Zhu Junming , Zhang Shaomin , Xi Wang , Wu Hemmings
Published: February 2024

Understanding the adaptability of the motor cortex in response to bilateral motor tasks is crucial for advancing our knowledge of neural plasticity and motor learning. Here we aim to investigate the dynamic lateralization of contralateral-projecting corticospinal neurons (cpCSNs) during such tasks. Utilizing in vivo two-photon calcium imaging, we observe cpCSNs in mice performing a bilateral lever-press task. Our findings reveal a heterogeneous population dynamics in cpCSNs: a marked decrease in activity during ipsilateral motor learning, in contrast to maintained activity during contralateral motor learning. Notably, individual cpCSNs show dynamic shifts in their engagement with ipsilateral and contralateral movements, displaying an evolving pattern of activation over successive days. This suggests a flexible and learning-related reconfiguration in the cpCSN network, parallel to motor learning stages. Our findings suggest a complex reorganization in cpCSN activities, underscoring the dynamic nature of cortical lateralization in motor learning and offering insights for neuromotor rehabilitation.
Noncoplanar and chiral spin states on the way towards Néel ordering in fullerene Heisenberg models
Authors: Szabó Attila , Capponi Sylvain , Alet Fabien
Published: February 2024

Using a high-accuracy variational Monte Carlo approach based on group-convolutional neural networks, we obtain the symmetry-resolved low-energy spectrum of the spin-1/2 Heisenberg model on several highly symmetric fullerene geometries, including the famous C60 buckminsterfullerene. We argue that as the degree of frustration is lowered in large fullerenes, they display characteristic features of incipient magnetic ordering: Correlation functions show high-intensity Bragg peaks consistent with Néel-like ordering, while the low-energy spectrum is organized into a tower of states. Competition with frustration, however, turns the simple Néel order into a noncoplanar one. Remarkably, we find and predict chiral incipient ordering in a large number of fullerene structures.

Published by the American Physical Society
2024
Dirac-Majorana neutrinos distinction in four-body decays
Authors: Márquez Juan Manuel , Portillo-Sánchez Diego , Roig Pablo
Published: February 2024

A novel method to differentiate the effects of Dirac and Majorana (D-M) neutrinos in four-body decays has been discussed in [C. S. Kim , Inferring the nature of active neutrinos: Dirac or Majorana?, .]. There, it is concluded that the back-to-back kinematic scenario seems to avoid the constraint imposed by the “practical Dirac-Majorana confusion theorem,” as one does not need to fully integrate over neutrino and antineutrino momenta. In this paper, we propose to analyze radiative leptonic lepton-decays (ℓ→ℓ′νν¯γ), as an independent alternative process to study the possible Majorana nature of neutrinos. Our approach demonstrates that, in the back-to-back kinematic configuration (for the ℓ′−γ and ν−ν¯ systems, respectively), the distinction between Dirac and Majorana cases disappears when the inaccessible neutrino angle is integrated out, which might appear unexpected considering the claims in [C. S. Kim , Inferring the nature of active neutrinos: Dirac or Majorana?, .]. Our results apply in absence of nonstandard interactions, which can enhance generally the sensitivity to the neutrino nature.

Published by the American Physical Society
2024
Scaling dimension of the
4π
-flux monopole operator in four-flavor three-dimensional QED using lattice simulation
Authors: Karthik Nikhil , Narayanan Rajamani
Published: February 2024

We numerically address the issue of which monopole operators are relevant under renormalization group flow in three-dimensional parity-invariant noncompact QED with four flavors of massless two-component Dirac fermion. Using lattice simulation and finite-size scaling analysis of the free energy to introduce monopole-antimonopole pairs in N=4 and N=12 flavor noncompact QED3, we estimate the infrared scaling dimensions of monopole operators that introduce 2π and 4π fluxes around them. We first show that the estimates for the monopole scaling dimensions are consistent with the large-N expectations for N=12 QED3. Applying the same procedure in N=4 QED3, we estimate the scaling dimension of 4π flux monopole operator to be 3.7(3), which allows the possibility of the operator being irrelevant. This finding offers support to the scenario in which higher-flux monopoles are irrelevant deformations to the Dirac spin liquid phase that could be realized on certain non-bipartite lattices by forbidding 2π-flux monopoles.

Published by the American Physical Society
2024
Resonant pseudo-Dirac dark matter as a sub-GeV thermal target
Authors: Brahma Nirmalya , Heeba Saniya , Schutz Katelin
Published: February 2024

Dark matter (DM) could be a pseudo-Dirac thermal relic with a small mass splitting that is coupled off diagonally to a kinetically mixed dark photon. This model, particularly in the sub-GeV mass range, is a key benchmark for accelerator searches and direct detection experiments. Typically, the presence of even a tiny fraction of pseudo-Dirac DM in the excited state around the time of recombination would be excluded by DM annihilation bounds from the cosmic microwave background (CMB); thus, viable thermal histories must typically feature an exponential suppression of the excited state. We revisit assumptions about the thermal history in the resonant regime, where the dark photon mass is slightly more than twice the DM mass (to within ∼10%), leading to an s-channel resonance in the annihilation cross section. This resonance substantially reduces the couplings required for achieving the observed relic abundance, implying that in much of the parameter space, the DM kinetically decouples from the Standard Model well before the final DM relic abundance is achieved. We find that the excited state is not thermally depopulated in this regime. In spite of this, we find that the presence of the excited state does violate CMB bounds, even for arbitrarily small mass splittings. The present-day abundance of the excited state opens up the possibility of signatures that are usually not relevant for pseudo-Dirac DM, including indirect detection, direct detection, and self-interacting DM signatures.

Published by the American Physical Society
2024
Angular and energy distributions of positrons created in subcritical and supercritical slow collisions of heavy nuclei
Authors: Dulaev N. K. , Telnov D. A. , Shabaev V. M. , Kozhedub Y. S. , Maltsev I. A. , Popov R. V. , Tupitsyn I. I.
Published: February 2024

Positron creation probabilities as well as energy and angular distributions of outgoing positrons in slow collisions of two identical heavy nuclei are obtained within the two-center approach beyond the monopole approximation. The time-dependent Dirac equation for positron wave functions is solved with the help of the generalized pseudospectral method in modified prolate spheroidal coordinates adapted for variable internuclear separation. Depending on the nuclear charge, the results are obtained for both subcritical and supercritical regimes of the positron creation. The signatures of transition to the supercritical regime in the total positron creation probabilities and energy spectra are discussed. The angular distributions of emitted positrons demonstrate a high degree of isotropy.

Published by the American Physical Society
2024
Axion star explosions: A new source for axion indirect detection
Authors: Escudero Miguel , Pooni Charis Kaur , Fairbairn Malcolm , Blas Diego , Du Xiaolong , Marsh David J. E.
Published: February 2024

If dark matter is composed of axions, then axion stars form in the cores of dark matter halos. These stars are unstable above a critical mass, decaying to radio photons that heat the intergalactic medium, offering a new channel for axion indirect detection. We recently provided the first accurate calculation of the axion decay rate due to axion star mergers. In this work we show how existing data concerning the CMB optical depth leads to strong constraints on the axion photon coupling in the mass range 10−14  eV≲ma≲10−8  eV. Axion star decays lead to efficient reionization of the intergalactic medium during the dark ages. By comparing this nonstandard reionization with Planck legacy measurements of the Thomson optical width, we show that couplings in the range 10−14  GeV−1≲gaγγ≲10−10  GeV−1 are excluded for our benchmark model of axion star abundance. Future measurements of the 21 cm emission of neutral hydrogen at high redshift could improve this limit by an order of magnitude or more, providing complementary indirect constraints on axion dark matter in parameter space also targeted by direct detection haloscopes.

Published by the American Physical Society
2024
Detecting hidden states in stochastic dynamical systems
Authors: Succar Rayan , Boldini Alain , Porfiri Maurizio
Published: February 2024

Inferring the number of states of a stochastic system from partial measurements is a fundamental problem in physics, for which methodological tools remain scarce. It is sometimes difficult to distinguish the stochastic dynamical states from measurements, deceiving us into incorrect models and flawed understanding of natural phenomena. Here, we propose a model-free statistical framework, grounded in network and control theory, to estimate the number of states of a stochastic system from perceptible dynamics. The framework extends previous techniques for deterministic systems, based on the rank of ancillary matrices. We show applications of our approach to a variety of physics domains, such as statistical mechanics, biophysics, physical chemistry, and epidemiology.

Published by the American Physical Society
2024
Ion Channels in Critical Membranes: Clustering, Cooperativity, and Memory Effects
Authors: Suma Antonio , Sigg Daniel , Gallagher Seamus , Gonnella Giuseppe , Carnevale Vincenzo
Published: February 2024

Much progress has been made in elucidating the inner workings of voltage-gated ion channels, but less understood is the influence of lipid rafts on gating kinetics. Here we propose that state-dependent channel affinity for different lipid species provides a unified explanation for the experimentally observed behaviors of clustering, cooperativity, and hysteresis. We develop models of diffusing lipids and channels engaged in Ising-like interactions to investigate the collective behaviors driven by raft formation in critical membranes close to the demixing transition. The model channels demonstrate lipid-mediated long-range interactions, activation curve steepening, and long-term memory in ionic currents. These behaviors likely play a role in channel-mediated cellular signaling and suggest a universal mechanism for self-organization of biomolecular assemblies.

Published by the American Physical Society
2024
Data reduction in protein serial crystallography
Authors: Galchenkova Marina , Tolstikova Alexandra , Klopprogge Bjarne , Sprenger Janina , Oberthuer Dominik , Brehm Wolfgang , White Thomas A. , Barty Anton , Chapman Henry N. , Yefanov Oleksandr
Published: February 2024

Serial crystallography (SX) has become an established technique for protein structure determination, especially when dealing with small or radiation-sensitive crystals and investigating fast or irreversible protein dynamics. The advent of newly developed multi-megapixel X-ray area detectors, capable of capturing over 1000 images per second, has brought about substantial benefits. However, this advancement also entails a notable increase in the volume of collected data. Today, up to 2 PB of data per experiment could be easily obtained under efficient operating conditions. The combined costs associated with storing data from multiple experiments provide a compelling incentive to develop strategies that effectively reduce the amount of data stored on disk while maintaining the quality of scientific outcomes. Lossless data-compression methods are designed to preserve the information content of the data but often struggle to achieve a high compression ratio when applied to experimental data that contain noise. Conversely, lossy compression methods offer the potential to greatly reduce the data volume. Nonetheless, it is vital to thoroughly assess the impact of data quality and scientific outcomes when employing lossy compression, as it inherently involves discarding information. The evaluation of lossy compression effects on data requires proper data quality metrics. In our research, we assess various approaches for both lossless and lossy compression techniques applied to SX data, and equally importantly, we describe metrics suitable for evaluating SX data quality.
The shortcomings of equal weights estimation and the composite equivalence index in PLS-SEM
Authors: Hair Joseph F. , Sharma Pratyush N. , Sarstedt Marko , Ringle Christian M. , Liengaard Benjamin D.
Published: February 2024

Purpose

The purpose of this paper is to assess the appropriateness of equal weights estimation (sumscores) and the application of the composite equivalence index (CEI) vis-à-vis differentiated indicator weights produced by partial least squares structural equation modeling (PLS-SEM).

Design/methodology/approach

The authors rely on prior literature as well as empirical illustrations and a simulation study to assess the efficacy of equal weights estimation and the CEI.

Findings

The results show that the CEI lacks discriminatory power, and its use can lead to major differences in structural model estimates, conceals measurement model issues and almost always leads to inferior out-of-sample predictive accuracy compared to differentiated weights produced by PLS-SEM.

Research limitations/implications

In light of its manifold conceptual and empirical limitations, the authors advise against the use of the CEI. Its adoption and the routine use of equal weights estimation could adversely affect the validity of measurement and structural model results and understate structural model predictive accuracy. Although this study shows that the CEI is an unsuitable metric to decide between equal weights and differentiated weights, it does not propose another means for such a comparison.

Practical implications

The results suggest that researchers and practitioners should prefer differentiated indicator weights such as those produced by PLS-SEM over equal weights.

Originality/value

To the best of the authors’ knowledge, this study is the first to provide a comprehensive assessment of the CEI’s usefulness. The results provide guidance for researchers considering using equal indicator weights instead of PLS-SEM-based weighted indicators.
“I didn’t want to promote it with a white girl”: marketing practices and boundary work at popular music festivals
Authors: Swartjes Britt
Published: February 2024

Purpose

This paper aims to explore how music festival organisers negotiate diversity and inclusion in marketing and promotion practices through symbolic and social boundaries.

Design/methodology/approach

Based on semi-structured interviews with 18 festival organisers in Rotterdam and participant observation with six festival photographers I show that symbolic and social boundaries are employed in three areas: (1) boundaries in festival format (i.e. [partially] free or ticketed), (2) boundaries in distribution partners and technologies and (3) boundaries in promotional content.

Findings

Symbolic and social boundaries are intentionally used by festival organisers to build and delineate festival audiences. Implications are drawn on current understandings of the accessibility of music festival spaces, arguing that festival research should move beyond within-space dynamics to grasp the negotiation of diversity and inclusion at festivals more fully.

Originality/value

While music festivals are often marketed as celebratory spaces that are “welcoming to everyone”, few studies have investigated diversity and inclusion nor marketing and promotion practices at music festivals. This study shows how festival audiences are shaped through marketing and promotion practices.
Students' learning outcomes from being a mentor in the Nightingale Mentoring Programme for Adult Refugees in Norway
Authors: Glømmen Anne Margrethe , Brevik Sæthern Beate , Eriksson Rikard
Published: February 2024

Purpose

This study aimed to identify and describe how mentoring influences the mentor, by operationalising and specifying learning outcomes involved in mentoring.

Design/methodology/approach

This study used an action research approach, by uniting theory and practice to explore new ways of learning and evolve the field of practice in education. Thematic analysis was used to identify and organise patterns or themes that emerged from the data.

Findings

The results showed that mentoring changed the mentors' perspectives towards improved understanding, more flexibility and approval of other cultures. It seems that mentoring expanded the mentors' search for values, wishes and resources, including an awareness that our values, wishes and needs are more similar than different. Mentoring also seems to have improved the ability to reformulate, be flexible, strive to optimise user engagement and engage with people as they are, based on their own prerequisites.

Research limitations/implications

The low number of participants means the results cannot be generalised, and voluntary participation may have led to more motivated involvement and positive results.

Practical implications

This study shows that mentoring has had an impact on students' development of intercultural competence and cultural sensitivity through regular meetings with individuals from a different cultural background. Mentoring seems to have revealed insights into underlying prejudices and changed perspectives towards better understanding, thus increased acceptance of other cultures.

Originality/value

Search for similar studies shows a lack of research that operationalises and specifies the learning outcomes that mentors gain from being a mentor.
How does social media use in the workplace affect employee voice? Uncovering the mediation effects of social identity and contingency role of job-social media fit
Authors: Chen Wenjing , Zheng Bowen , Liu Hefu
Published: February 2024

Purpose

Employee voice is crucial for organizations to identify problems and make timely adjustments. However, promoting voice in organizations is challenging. This study aims to investigate how social media use (SMU) in the workplace affects employee voice by examining its intrinsic mechanisms and boundary conditions. Specifically, this study examines the mediating roles of social identifications and the moderating effects of job-social media fit on the relationship between SMU and social identifications.

Design/methodology/approach

This study conducted a survey of 348 employees in China.

Findings

First, SMU affects voice through social identifications. Second, distinct identifications have different effects on voice, such that organizational identification positively affects employee voice, while relational identification positively affects promotive voice and negatively affects prohibitive voice. Third, when social media is highly suitable for the job, the positive effect of work-related SMU on organizational identification is strengthened, while the positive effect of social-related SMU on organizational identification is weakened.

Originality/value

The results indicate that different identifications have distinct impacts on voice. Additionally, this study reveals a double-edged sword effect of SMU on voice through different social identifications. Further, job-social media fit moderates the relationship between SMU and social identifications. These findings have important implications for organizations adopting social media.
Investigating student’s motivation and online learning engagement through the lens of self-determination theory
Authors: Ojo Adedapo Oluwaseyi , Ravichander Sumitha , Tan Christine Nya-Ling , Anthonysamy Lilian , Arasanmi Chris Niyi
Published: February 2024

Purpose

The lack of physical contact and the absence of nonverbal clues could make some learners uncomfortable interacting with others via online learning platforms. Hence, understanding the determinants of students' motivation and engagement in online learning platforms is crucial in harnessing digital technology as an enabler of unrestricted and quality learning experiences.

Design/methodology/approach

Drawing on the self-determination theory (SDT), this study investigates the factors associated with student’s motivation to learn (MOL) and their influence on online learning engagement (OLE). Data were collected from 228 university students from the Klang Valley region of Malaysia using the online survey method.

Findings

The results of data analysis using the partial least squares structural equation modeling indicate that self-directed learning, computer and Internet self-efficacy and online communication self-efficacy significantly influence MOL. Besides, these factors indirectly influence OLE through MOL.

Originality/value

This study adds to the SDT framework by demonstrating how students' perceptions of autonomy, competence and relatedness through online interaction relate to MOL and OLE.
Understanding ways to support teens and parents affected by Russia–Ukraine war
Authors: Lopatovska Irene , Coan Celia
Published: February 2024

Purpose

The study explored how information institutions can support the resilience of parents of adolescents affected by the Russia–Ukraine war. Ukrainian parents are facing major challenges of supporting their teenagers through a difficult developmental phase while also “buffering” their war-related hardships. By supporting parents, information institutions can also support children.

Design/methodology/approach

Fifteen parents were interviewed about mental health challenges and resources that are helpful and/or missing from their support systems. Recordings of participant narratives were analyzed using the qualitative thematic analysis technique.

Findings

The findings indicate that both teens and parents rely on internal resilience skills, family, friends and community resources to support themselves. However, a number of additional resources could be offered by information institutions, including content for (1) teens on developing skills in communication, interpersonal relationships, problem solving and academic pursuits; (2) parents on child development and opportunities in their host countries; both groups on (3) both groups on mental health first aid and safe spaces to meet peers. The study recommendations will be of interest to information professionals working with families, especially families affected by disasters.

Research limitations/implications

The study relied on a small convenience sample of participants.

Practical implications

Study recommendations would be of interest to information professionals who develop and provide services to families affected by natural and manmade disasters.

Social implications

Study recommendations improve understanding of the (potential) role of information institutions and libraries in strengthening family and community resilience.

Originality/value

The study offers a rare insight into experiences of war-affect families and provides evidence-driven recommendations for information institutions to support family and community resilience.
The role of emotional solidarity–driven tourists’ nostalgia in shaping advocacy intentions
Authors: Razzaq Sadaf , Akhtar Naeem
Published: February 2024

Purpose

Examining emotional solidarity that drives tourists’ nostalgia has received significant attention, offering valuable insights that can aid in the selection of a travel destination. However, tourists’ nostalgia, along with its antecedents—perceived safety risk and emotional solidarity, has gained less attention within the setting of Pakistan. Therefore, this research has been carried out and validated a research framework using the stimulus-organism-response model to investigate the links between perceived safety risk, emotional solidarity—welcoming nature, emotional closeness, sympathetic understanding, perceived nostalgia, and destination advocacy intentions. In addition, this model employed destination attachment—place identity and place dependence—as a boundary condition on the relationships between emotional solidarity and advocacy intentions.

Design/methodology/approach

This study collected 545 responses through two methods: offline distribution of print copies of the questionnaire and online surveys from domestic tourists who visited scenic destinations last year. Structural equation modeling (SEM) was performed using AMOS 26, and the PROCESS macro was conducted using IBM SPSS 28.

Findings

The findings highlighted that perceived safety risk negatively influences emotional solidarity—welcoming nature, emotional closeness, sympathetic understanding—, resulting in a positive effect on perceived nostalgia. Furthermore, tourists’ perceived nostalgia positively triggers advocacy intentions. The findings also confirmed the boundary conditions of destination attachment—place identity and place dependence—on the association between emotional solidarity and perceived nostalgia.

Practical implications

Three major practical implications of these findings: First, ensuring visitor safety with smart security measures, digital tools for quick response, and local community involvement. Second, highlighting local markets, art, and architecture to enrich cultural experiences and promote accessibility and diversity. Finally, using marketing to generate nostalgic experiences through local collaborations, professional storytelling, and engaging social media content to build emotional ties and curiosity.

Originality/value

In terms of originality, this is pioneering research intended at developing and validating the model in the context of Pakistani destinations. Furthermore, this marks the initial step in examining the proposed relationships between perceived safety risk and emotional solidarity in fostering tourists' perceived nostalgia, ultimately leading to a strong desire to advocate for the destination.
Evolving a conceptual framework for sustainable e-waste management: a consumer typology based on environmental behavior
Authors: Vighnesh Nanjangud Vishwanath , Patil Balachandra , Chandrashekar Deepak
Published: February 2024

Purpose

There is widespread consensus that unchecked growth of e-waste is a major challenge to global sustainability transition. Current research has failed to connect e-waste with principles of circularity and sustainability from the consumption perspective. This paper aims to answer the following questions: What kind of environmental behaviors (EBs) exist among consumers in relation to e-waste?; In what ways are these consumers different from and similar to each other based on their EBs in relation to e-waste?; How do consumers and their EBs contribute to sustainable waste management?

Design/methodology/approach

Based on primary data from an Indian sample of information and communication technology consumers, EBs relevant to e-waste management are identified. In the next stage, a behavior-based segmentation and profiling of consumers is performed.

Findings

The first phase of analysis produced eight distinct EBs which were then used in the next phase to obtain a consumer typology of three segments. The three consumer segments differed significantly with each other on general environmental behavior and awareness about e-waste.

Research limitations/implications

The paper develops a comprehensive conceptual framework for studying the demand-side circularity transition for sustainable e-waste management.

Practical implications

For business stakeholders, findings of the study and the proposed framework can inform behavior change interventions to customize offerings for different right consumer segments.

Originality/value

The paper adds new knowledge to the intersectional area of e-waste, consumer behavior and sustainability through the development of consumer typology and a conceptual framework.