bluuebunny/crossref_metadata_2025 huggingface dataset:
Where do I go? Decoding temporal neural dynamics of scene processing and
visuospatial memory interactions using CNNs
Authors: Naveilhan Clément , Zory Raphaël , Ramanoël Stephen
Published: January 2025

Visual scene perception enables rapid interpretation of the surrounding
environment by integrating multiple visual features related to task demands and
context, which is essential for goal-directed behavior. In the present work, we
investigated the temporal neural dynamics underlying the interaction between the
processing of visual features
(i.e., bottom-up
processes) and contextual knowledge
(i.e., top-down
processes) during scene perception. We analyzed EEG data from 30 participants
performing scene memory and visuospatial memory tasks in which we manipulated
the number of navigational affordances available
(i.e., the number of
open doors) while controlling for similar low-level visual features across
tasks. We used convolutional neural networks (CNN) coupled with
gradient-weighted class activation mapping (Grad-CAM) to assess the main
channels and time points underlying neural processing for each task. We found
that early occipitoparietal activity (50-250 ms post-stimulus) contributed most
to the classification of several aspects of visual perception, including scene
color, navigational affordances, and spatial memory content. In addition, we
showed that the CNN successfully trained to detect affordances during scene
perception was unable to detect the same affordances in the spatial memory task
after learning, whereas a similarly trained and tested model for detecting wall
color was able to generalize across tasks. Taken together, these results reveal
an early common window of integration for scene and visuospatial memory
information, with a specific and immediate influence of newly acquired spatial
knowledge on early neural correlates of scene perception.
Neural dynamics hierarchy in motor cortex and striatum across naturalistic
behaviors
Authors: Xing David , Glaser Joshua , Miri Andrew
Published: January 2025

Mammals perform a wide range of movements actuated by diverse patterns of
muscle activity. Primary motor cortex (M1) and striatum are implicated in
controlling these movements, but how their activity dynamics are organized to
accommodate such diversity is poorly understood. We developed a paradigm that
enabled us to investigate neural dynamics across diverse motor behaviors in
mice. In contrast to existing views, we found neither behavior-specific nor
behavior- invariant organization in single-neuron activity, population-level
covariation, and muscle activity correlation. Instead, the similarity of
activity dynamics between behaviors varied differentially across behavior pairs,
forming a hierarchical organization. The same hierarchical organization was
shared between M1 and striatum, despite stronger muscle activity correlation in
M1 and greater behavior specificity in striatum. Network modeling indicated that
striatal activity is sufficient to drive hierarchical dynamics in muscle
pattern-generating circuits. These hierarchical dynamics may reflect a tradeoff
between behavioral specialization and generalization in motor system
function.
Species-specific oxygen sensing governs the initiation of vertebrate limb
regeneration
Authors: Tsissios Georgios , Leleu Marion , Hu Kelly , Demirtas Alp Eren , Hu Hanrong , Kawanishi Toru , Skoufa Evangelia , Valente Alessandro , Herrera Antonio , Mery Adrien , Noseda Lorenzo , Ochi Haruki , Sakar Selman , Tanaka Mikiko , Zenk Fides , Aztekin Can
Published: January 2025

Why mammals cannot regenerate limbs, unlike amphibians, presents a
longstanding puzzle in biology. We show that exposingex
vivoamputated embryonic mouse limbs to subatmospheric oxygen
environment, or stabilizing oxygen-sensitive HIF1A enables not only rapid wound
healing, but alters cellular mechanics, and reshapes the histone landscape to
prime regenerative fates. Conversely,
regenerativeXenopustadpole limbs display low
oxygen-sensing capacity, robust wound healing, a regenerative histone landscape,
and glycolytic programs even under high oxygen. This reduced oxygen-sensing
capacity, in stark contrast to mammals, associates with decreased
HIF1A-regulating gene expressions. Our findings thus uncover species-specific
oxygen sensing as a unifying mechanism for limb regeneration initiation across
vertebrates, reveal how aquatic subatmospheric habitats may enhance regenerative
capabilities, and identify targetable barriers to unlock latent limb
regenerative programs in adult mammals.
Infectivity of a pathogenicity-attenuatedChlamydia muridarummutant in
the genital tract
Authors: Li Caiting , Liu Zhaoyang , Hua Yaoqin , Ma Chunguang , Zhong Guangming
Published: January 2025

AC. muridarummutant designated as intrOv was
evaluated as
anintracellularOral
vaccinevector because it can induce protection in
the genital tract following oral inoculation but does not elicit genital
pathology following intravaginal infection. However, the mechanism of intrOv’s
attenuation is unclear. Here we report that few live organisms were recovered
from vaginal swabs during the early stage of intrOv intravaginal infection in
mice. At a low inoculating dose, an isogenic wild-type control strain
established a productive infection, while intrOv failed to do so. Although a
higher inoculating dose allowed intrOv and its control to productively infect
mice, fewer live intrOv than the control organisms were recovered from the lower
genital tract tissues on day 3 post-infection. By day 7, animals infected with
intrOv or the control shed similar numbers of live organisms, suggesting the
intrOv’s deficiency on day 3 was transient. Consistently, intrOv reduced
invasion of epithelial cells but maintained as robust intracellular replication
as its control. Our results correlate intrOv’s delay in infecting the lower
genital tissues and reduction in invading epithelial cells with its attenuation
in genital pathogenicity, laying the foundation for further revealing the
mechanisms of the intrOv’s attenuation in pathogenicity during genital tract
infection.
Genomics of experimental adaptive radiation in the cryptic coloration of
feather lice
Authors: Baldwin-Brown James , Villa Scott M. , Waight Emiko , Johnson Kevin P. , Bush Sarah E. , Clayton Dale H. , Shapiro Michael D.
Published: January 2025

1

A major challenge faced by living organisms is adaptation to novel
environments. This process is poorly understood because monitoring genetic
changes in natural populations is difficult. One way to simplify the task is to
focus on organisms that can be studied in captivity under conditions that remain
largely natural. Feather lice (Insecta, Phthiraptera, Ischnocera) are
host-specific parasites of birds that live, feed, and breed solely on feathers.
Birds defend themselves against lice, which damage feathers, by killing them
with their beaks during bouts of preening. In response, feather lice have
evolved background-matching cryptic coloration to help them avoid preening. We
experimentally manipulated the color backgrounds of host-specific pigeon lice
(Columbicola columbae) by confining them to
different colored breeds of rock pigeon (Columba
livia) over a period of four years (ca. 60 louse generations).
Over the course of the experiment, we sampled lice from pigeons every six months
for genomic resequencing, and then calculated allele frequency differences and
trajectories to identify putative genomic sites under selection. We documented
many loci that changed in response to selection for color. Most loci putatively
under selection were unshared among replicate populations of lice, indicating
that independent adaptation of distinct lineages to the same novel environment
resulted in similar phenotypes driven by different genotypes.
Expression patterns of blood-based biomarkers of neurodegeneration and
inflammation across adulthood in rhesus macaques
Authors: Metzler Ludwig A.P. , Metzger Jeanette M. , Gerred Keenan J. , Emborg Marina E. , Kapoor Amita
Published: January 2025

As the global human population rapidly ages and diseases of aging become
more prevalent, preclinical models of age-related neurodegenerative disorders
are increasingly important for identifying early diagnostic biomarkers,
monitoring disease progression, and evaluating treatment responsiveness. Rhesus
macaques are an ideal species for studies on neurodegeneration due to their
phylogenetic relatedness to humans and their complex brain anatomy and
physiology. Technological advances in assay sensitivity have facilitated the
identification of blood-based biomarkers of neurodegeneration and inflammation
in human populations. The aim of this study was to translate these methods for
use in male and female rhesus macaques across adulthood. We collected plasma
samples from 47 rhesus macaques representing pre-adult (1-5 years, n=6 female,
n=5 male), young (5-7 years, n=5 female, n=7 male), middle (8-16 years, n=7
female, n=7 male), and older adult (17-22 years, n=6 female, n=4 male) subjects.
Quantified biomarkers included neurofilament light chain (NfL), glial fibrillary
acidic protein (GFAP), amyloid beta (Aβ42, Aβ40, and their ratio), total tau,
phosphorylated tau (pTau181), interleukin (IL) 2, IL-6, IL-8, and IL-10. Plasma
NfL and IL-6 levels were significantly increased with age in both sexes, with a
marked rise during middle adulthood. The ratio of Aβ42/Aβ40 significantly
declined steadily with age, mirroring the aging pattern described in humans.
There was no effect of age or sex on total tau or pTau181 levels. Overall, these
results demonstrate the feasibility of evaluating blood biomarkers of
neurodegeneration and inflammation in rhesus macaques during adulthood.
Finding Salient Multi-Omic Interactomes Relevant to Multiple Biomedical
Outcomes using Graph Ensemble Neural Networks
Authors: Eicher Tara , Chan Jany , Becker Aline P. , Haque S. Jaharul , Fleming Jessica , McElroy Joseph , Meng Wei , Webb Amy , Kelly Rachel S. , Celedón Juan , Clish Clary , Gerszten Robert , McGeachie Michael , Weiss Scott T. , Lasky-Su Jessica , Chakravarti Arnab , Mathé Ewy A. , Machiraju Raghu
Published: January 2025

Although multi-omics integration relevant to patient outcome is typically
characterized by an analyte interactome, current multi-omic integration methods
either (1) model outcome without directly including associations between
analytes, (2) model the interactome without directly evaluating the saliency of
the model in the context of outcome, or (3) model outcome in a high-dimensional
parameter space not suitable for small sample sizes (which are common in
multi-omics studies). We introduce Graph Ensemble Neural Network (GENN), a
methodology that learns the interactome most predictive of outcome in a
low-dimensional parameter space built on complementary attributes for all
possible analyte associations (metafeatures). We show
that GENN is robust to noise in measurements using a theoretical model,
outperforms the predictive performance of existing methods when evaluated on
Tegafur drug response in NCI-60 cancer cell line data, and uncovers potentially
novel multi-omic mechanisms driving total serum IgE levels in pediatric asthma
and patient survival in glioblastomas.
Dissociable neurofunctional and molecular characterizations of reward and punishment sensitivity
Authors: Xu Ting , Zhu Chunhong , Zhou Xinqi , Chen Zhiyi , Gan Xianyang , Cui Xiaobing , Zhou Feng , Zhang Ran , Zhao Weihua , Zhang Xiaodong , Chen Hong , He Qinghua , Lei Xu , Qiu Jiang , Feng Tingyong
Published: January 2025

While the hyper-and hypo-reward or punishment sensitivities (RS, PS) have received considerable attention as prominent transdiagnostic features of psychopathology, the lack of an overarching neurobiological characterization currently limits their early identifications and neuromodulations. Here we combined microarray data from the Allen Human Brain Atlas with a multimodal fMRI approach to uncover the neurobiological signatures of RS and PS in a discovery-replication design (N=655 participants). Both RS and PS were mapped separately in the brain, with the intrinsic functional connectome in the fronto-striatal network encoding reward responsiveness, while the fronto-insular system was particularly engaged in punishment sensitivity. This dissociable functional connectome patterns related to RS and PS were also specific in differentiating decisions driven by social or monetary reward and punishment motivations. Further imaging transcriptomic analyses revealed that functional connectome variations for RS and PS were associated with topography of specific gene sets enriched in ontological pathways, including synaptic transmission, dopaminergic metabolism, immune response and stress adaptation. On the neurotransmitter level, the serotonin neuromodulator was identified as a pivotal hub regulating the intrinsic functional connectome patterns of RS and PS, with this process critically dependent on its interactions with dopaminergic, opioid and GABAergic systems. Overall, these findings indicate dissociable neural connectome mapping of RS and PS and highlight their linkage with transcriptomic profiles, which may offer valuable insights into the treatment evaluation for symptomatology relevant to reward/punishment processing deficits.
Widespread 3D genome reorganization precedes programmed DNA rearrangement inOxytricha trifallax
Authors: Villano Danylo J. , Prahlad Manasa , Singhal Ankush , Sanbonmatsu Karissa Y. , Landweber Laura F.
Published: January 2025

Genome organization recapitulates function, yet ciliates likeOxytricha trifallaxpossess highly-specialized germline genomes, which are largely transcriptionally silent. During post-zygotic development,Oxytricha’s germline undergoes large-scale genome editing, rearranging precursor genome elements into a transcriptionally-active genome with thousands of gene-sized nanochromosomes. Transgenerationally-inherited RNAs, derived from the parental somatic genome, program the retention and reordering of germline fragments. Retained and eliminated DNA must be distinguished and processed separately, but the role of chromatin organization in this process is unknown. We developed tools for studyingOxytrichanuclei and apply them to map the 3D organization of precursor and developmental states using Hi-C. We find that the precursor conformation primes the germline for development, while a massive spatial reorganization during development differentiates retained from eliminated regions before DNA rearrangement. Further experiments suggest a role for RNA-DNA interactions and chromatin remodeling in this process, implying a critical role for 3D architecture in programmed genome rearrangement.
A multipurpose microhaplotype panel for genetic analysis of California Chinook salmon
Authors: Anderson Eric C. , Clemento Anthony J. , Campell Matthew A. , Pearse Devon E. , Beulke Anne K. , Columbus Cassie , Campbell Ellen , Thompson Neil F. , Garza John Carlos
Published: January 2025

Genetic methods have become an essential component of ecological investigation and conservation planning for fish and wildlife. Among these methods is the use of genetic marker data to identify individuals to populations, or stocks, of origin. More recently, methods that involve genetic pedigree reconstruction to identify relationships between individuals within populations have also become common. We present, here, a novel set of multi-allelic microhaplotype genetic markers for Chinook salmon which provide unprecedented resolution for population discrimination and relationship identification from a rapidly and economically assayed panel of markers. We show how this set of microhaplotypes provides definitive power to identify all known lineages of Chinook salmon in California. The inclusion of genetic loci that have known associations with phenotype and that were identified as outliers in examination of whole genome sequence data, allows resolution of stocks that are not highly genetically differentiated but are phenotypically distinct and managed as such. This same set of multiallelic genetic markers have ample variation to accurately identify parent-offspring and full-sibling pairs in all California populations, including the genetically depauperate winter-run lineage. Validation of this marker panel in coastal salmon populations not previously studied with modern genetic methods, also reveals novel biological insights, including the presence of a single copy of a haplotype for a phenotype that has not been documented in that part of the species range, and a clear signal of mixed ancestry for a salmon population that is on the geographic margins of the primary evolutionary lineages present in California.
Balancing doses of EL222 and light improves optogenetic induction of protein production inKomagataella phaffii
Authors: Hoffman Shannon M. , Espinel-Ríos Sebastián , Lalwani Makoto A. , Kwartler Sarah K. , Avalos José L.
Published: January 2025

Komagataella phaffii, also known asPichia pastoris, is a powerful host for recombinant protein production, in part due to its exceptionally strong and tightly controlled PAOX1promoter. MostK. phaffiibioprocesses for recombinant protein production rely on PAOX1to achieve dynamic control in two-phase processes. Cells are first grown under conditions that repress PAOX1(growth phase), followed by methanol-induced recombinant protein expression (production phase). In this study, we propose a methanol-free approach for dynamic metabolic control inK. phaffiiusing optogenetics, which can help enhance input tunability and flexibility in process optimization and control. The light-responsive transcription factor EL222 fromErythrobacter litoralisis used to regulate protein production from the PC120promoter inK. phaffiiwith blue light. We used two system designs to explore the advantages and disadvantages of coupling or decoupling EL222 integration with that of the gene of interest. We investigate the relationship between EL222 gene copy number and light dosage to improve production efficiency for intracellular and secreted proteins. Experiments in lab-scale bioreactors demonstrate the feasibility of the outlined optogenetic systems as potential alternatives to conventional methanol-inducible bioprocesses usingK. phaffii.
Scaly-Tail Organ Enhances Static Stability during Pel’s Scaly-tailed Flying Squirrels’ Arboreal Locomotion
Authors: Schulz Andrew K. , Chellapurath Mrudul , Khandelwal Pranav C. , Rezaei SeyedReza , Merker Stefan , Jusufi Ardian
Published: January 2025

Scaly-tailed squirrels (Anomaluridae) are one of the least studied mammalian families. Their namesake is due to a peculiar and unique scaly-tail organ extruding from the caudal vertebrate that has been predicted to help reduce skidding. This study investigates the function of the scaly-tail organ found inAnomalurus pelii, investigating its potential role in enhancing arboreal locomotion. As these animals glide from tree to tree in a habitat abundant with smooth-bark trees, we hypothesize that the scaly-tail organ assists with friction enhancement in their native smooth-bark habitat. Through a combination of analyses using mathematical and physical models for experimental validation, we explore whether the scaly-tail organ could improve the sliding and overturning stability during perching. Our experimental results showed that the scaly-tail organ can act as a skid-reduction mechanism by enhancing substrate engagement on intermediate roughness substrates by 58%. Mathematical models showed the scaly-tail organ enhances overturning stability by acting as an additional support point. Our model showed that the scaly-tailed squirrel can reach up to 82.5◦inclination without claw force; however, without scales, it reduces to 79.6◦. Overall, this research highlights the functional significance of scaly-tail organs in adaptations in scaly-tailed flying squirrels and contributes to our understanding of their locomotion strategies and environmental stresses. Our study also provides insights into innovative perching mechanisms for robots operating in arboreal environments.
Unexpected D-tour Ahead: Why the D-Statistic, applied to Humans, Measures Mutation Rate Variation not Neanderthal Introgression
Authors: Amos William , Elhaik Eran
Published: January 2025

It is widely accepted that humans interbred with Neanderthals and other extinct hominins, leaving a lasting genetic legacy. However, much of the supporting evidence was developed using the statistic D, which assumes, without testing, both that mutation rate is constant and that recurrent mutations are vanishingly rare. These assumptions together preclude an alternative explanation based on variation in mutation rates across human populations. Here we critically evaluate the assumptions underlying D and confirm that neither is valid. Over 40% of SNPs in dbSNP carry recurrent mutations. Theory indicates that D does not vary with mutation rate as long as the mutation rate does not vary between populations. In practice, D calculated separately for different sequence motifs varies greatly, implying strongly that mutation rates do vary between populations. We show that most, if not all, D-informative sites result from two mutations rather than the one mutation expected under the introgression hypothesis. Moreover, individual non-Africans carry a signal in more than five times as many genomic windows as can be accounted for by the 2% legacy they are thought to carry, indicating a signal that is radically more diffuse than expected. Remarkably, partitioning the data by whether the chimpanzee or Neanderthal allele is the major allele in humans reveals that the overall reported D-value of ∼5% actually comprises two opposing components: one with D ∼ 30% and another with D ∼ -25%. Tellingly, the positive component is produced by sites where the Neanderthal allele is themajorallele, the exact opposite of what should be the case under introgression, where introgressed alleles should be rare. We show further that the entire D signal can be accounted for by sites where the Neanderthal allele is fixed outside Africa and the chimpanzee allele is rare inside Africa. Investigating potential mechanisms, we extend the published observation that the mutability of three-base combinations across human populations is influenced by flanking sequence heterozygosity to reveal how genomic regions that lost more heterozygosity out of Africa exhibit higher D-values. This correlation supports a model where loss of heterozygosity slowed the mutation rate, thereby reducing the divergence between Neanderthals and non-Africans. Across independent tests, our findings consistently indicate that the mutation rate variation hypothesis provides a more compelling explanation for the observed patterns in human-Neanderthal genetic relationships than the introgression hypothesis. We argue that the mutation rate variation hypothesis would help settle a number of conflicting patterns in the literature and, hence, that the concept of archaic introgression into humans and its implications for hominin-derived traits warrants reconsideration.
The bully phage: A Shiga toxin-encoding prophage interferes with the induction of co-hosted prophages
Authors: Hashuel Rachel , Wellins Tamara , Rachimi Maayan , Gutman Eran , Melki Reut , Taktuk Linoy , Wasserzug Pe’era Pash , Avissar Rinat , Roitman Karina , Litvak Yael
Published: January 2025

Shiga toxin (Stx) prophages lysogenize various bacterial species, converting them into dangerous pathogens and driving the ongoing emergence of new outbreaks globally. These pathogens are polylysogens, harboring multiple prophages within their genomes. Yet, the impact of Stx prophage acquisition on resident prophages remains largely unknown. Usingin vivotransmission studies with the murine pathogenCitrobacter rodentiumthat carries an Stx prophage, we demonstrate that the Stx prophage readily lysogenizes commensalEscherichia colistrains within the intestine. Markedly, this lysogenization altered the induction activity of prophages encoded within each new toxigenic host strain. Moreover, the Stx prophage abolished the induction of ϕNP, the most active native prophage ofC. rodentium. We further show that ϕNP inhibition is mediated by the Stx Cro repressor, which exhibits dual functionality, promoting its own lytic cycle while repressing the expression of ϕNP lytic genes. Our findings reveal a novel competition strategy among prophages, and suggest that interfering with the induction of co-hosted prophages likely plays a role in the emergence and evolution of new Stx-producing pathogens.
Modelling symplasmic transport: from biophysical basics to steeper root gradients
Authors: Deinum Eva E. , Marée Athanasius F. M. , Benitez-Alfonso Yoselin , Grieneisen Verônica A.
Published: January 2025

Development and spatial pattern formation are inherently linked. The coordinated determination of cell fates is crucial in any developmental process and requires extensive intercellular communication. Plants cells exchange many molecular signals via the symplasmic pathway, i.e., via plasmodesmata: narrow channels connecting the cytoplasm of neighbouring cells. Regulation of symplasmic transport is vital for normal plant development, and mutations that disrupt this regulation are often embryo or seedling lethal. In many tissues, symplasmic transport of small molecules is diffusion driven, resulting in a non-selective and bidirectional transport, although net directionality could arise from gradients. This has led to the (dogmatic) belief that symplasmic transport can only be detrimental to pattern formation, because signalling molecules cannot be confined, and gradients would fade. Here, we develop a detailed biophysical description of symplasmic transport to explore how plasmodesmata affect gradients in a linear tissue. We then apply the model in more complex tissue contexts, observing and explaining, e.g., that symplasmic transport may result insteepergradients in the root apical meristem. In conclusion, our model provides a reference framework for estimating the consequences of symplasmic transport and explains how symplasmic transport can contribute to more robust developmental patterning.
Molecular basis for shifted receptor recognition by an encephalitic arbovirus
Authors: Fan Xiaoyi , Li Wanyu , Oros Jessica , Plung Jesse S. , Plante Jessica A. , Basu Himanish , Nagappan-Chettiar Sivapratha , Boeckers Joshua M. , Tjang Laurentia V. , Mann Colin J. , Brusic Vesna , Buck Tierra K. , Varnum Haley , Yang Pan , Malcolm Linzy M. , Choi So Yoen , de Souza William M. , Chiu Isaac M. , Umemori Hisashi , Weaver Scott C. , Plante Kenneth S. , Abraham Jonathan
Published: January 2025

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from 1941–2005 bound to mammalian receptors, we identify polymorphisms in the WEEV spike protein that explain shifts in receptor dependencies and that can allow nonpathogenic strains to infect primary cortical neurons. We predict the receptor dependencies of additional strains and of a related North American alphavirus. Our findings have implications for outbreak preparedness and enhance understanding of arbovirus neurovirulence through virus receptor binding patterns.
The sex-specific effects of RAGE signaling and Type 2 Diabetes on mouse cortical bone mechanics, structure, and material properties
Authors: Hung Timothy , Broz Kaitlyn S , Walk Remy E , Tang Simon Y
Published: January 2025

Individuals with type 2 diabetes (T2D) are prone to fracture at numerous skeletal sites despite presenting with a higher bone mineral density (BMD). The accumulation of Advanced Glycation End-products (AGEs) in the bone tissues of patients with T2D could be contributing to this paradox, of increased skeletal fragility with higher BMD. AGEs can impair bone cell homeostasis via the receptor for AGEs (RAGE). To investigate the effects of diabetes, AGE accumulation, and RAGE signaling on mouse cortical bone, we utilized male and female leptin receptor-deficient (db/db) mice from three age groups ranging from 3-14 months of age, which were crossed with animals carrying constitutively RAGE-deficient alleles (RAGE−/−). The morphological, mechanical and material outcomes were measured using microCT, 3-pt bending, and an AGE assay. We observed significant impairments dependent on age and sex to the bone matrix and whole-bone mechanical behavior due to diabetes with some impairments alleviated with the ablation of RAGE. In older female diabetic mice, the removal of RAGE signaling prevented the deficits in bone mechanics, morphology and tissue mineral density (TMD). Male diabetic mice without RAGE signaling exhibited improved material properties. The study demonstrated that some bone impairments associated with T2D are prevented with RAGE ablation and may be partially reversible with the inhibition of RAGE signaling.

Graphical Abstract
Nuclear basket proteins Mlp1 and Nup2 drive heat shock-induced 3D genome restructuring
Authors: Mohajan Suman , Rubio Linda S. , Gross David S.
Published: January 2025

The nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here we address the role of the NPC in driving thermal stress-induced 3D genome repositioning ofHeat Shock Responsive(HSR) genes in yeast. We found that two nuclear basket proteins, Mlp1 and Nup2, although dispensable for NPC integrity, are required for drivingHSRgenes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment toHSRgene regulatory and coding regions.HSRgene clustering occurs predominantly within the nucleoplasm and is independent of the essential scaffold-associated proteins Nup1 and Nup145. Notably, double depletion of Mlp1 and Nup2 has little effect on the formation of Heat Shock Factor 1 (Hsf1)-containing transcriptional condensates, Hsf1 and Pol II recruitment toHSRgenes, orHSRmRNA abundance. Our results define a 3D genome restructuring role for nuclear basket proteins extrinsic to the NPC and downstream ofHSRgene activation.
Hydrodynamic cues enhance algal lipid production while sustaining biomass in motile species
Authors: Kakavand Narges , Sengupta Anupam
Published: January 2025

Achieving enhanced lipid yield without compromising biomass is one of the long-standing challenges in our quest to produce algal biofuel sustainably. Multiple factors, including temperature, nutrients and light conditions impact lipid production, however such lipid-enhancing strategies often lead to reduced biomass, thereby offsetting the total volume of lipid recovered. Hydrodynamic cues remain poorly studied, specifically in the context of lipid production in motile algae, concurrently with biomass generation and photo-physiology, a key fitness parameter. By imposing hydrodynamic cues to biophysically stress distinct strains of raphidophyteHeterosigma akashiwoat specific time points along the growth stages (indicating different nutritional states), we quantify the lipid production, alongside algal biomass and photo-physiology. Early induction (hydrodynamic cues implemented during the lag phase) and delayed induction (hydrodynamic cues implemented during the exponential phase) were studied. Delayed induction of hydrodynamic cues suppressed growth and photo-physiology without significant enhancement of lipid production, however, early induction allowed to significantly increase lipid content, up to 300%, without observable changes in biomass and photo-physiology. Based on this, we propose a hydrodynamic strategy for enhanced lipid production with sustained biomass and physiological fitness. This work presents hydrodynamic perturbation and its onset timing as tunable parameters to advance lipid production technologies across diverse motile species.
Solriamfetol enhances alertness and cognitive performance in mice
Authors: Haddar Meriem , Tzanoulinou Stamatina , Chen Li Yuan , Tafti Mehdi , Vassalli Anne
Published: January 2025

Solriamfetol [(R)-2-amino-3-phenylpropylcarbamate hydrochloride], a phenylalanine derivative initially developed as potential antidepressant, was shown by our group in 2009 to have potent, dose-dependent wake-promoting activity in mice. Solriamfetol (Sunosi®) is used since 2019 to counteract excessive daytime sleepiness (EDS) in patients with narcolepsy and obstructive sleep apnea (OSA). It has several advantages over other stimulants, notably that it is not associated with strong psychomotor activity, does not induce behavioral stereotypies and anxiety-related behaviors, in contrast to amphetamines and modafinil. Its mode-of-action remains incompletely solved. It was reported to act as dual dopamine-and-noradrenaline-reuptake-inhibitor (DNRI), and more recently, to have TAAR1 agonist activity. In our early mouse study, we showed that, at 150 mg/kg, Solriamfetol induces a state of wakefulness featuring a dramatic upregulation of EEG gamma activity, a cognitive biomarker, and the expression of genes implicated in neural plasticity, learning and memory. Besides being prescribed to treat EDS, central nervous system stimulants are commonly used as ‘smart drugs’ to enhance cognition in normal individuals. Therefore, based on Solriamfetol’s ability to potently induce wakefulness, EEG and molecular markers of learning and memory, we aimed to determine whether it could improve the cognitive performance of wild-type mice. Because at doses of 50-150 mg/kg, Solriamfetol induced an alert waking state associated with low mobility, thus precluding behavioral testing, we used lower doses (1-3 mg/kg) to assess cognition in a battery of tests evaluating short- or long-term memory and spatial navigation. We found that compared to saline, Solriamfetol 3 mg/kg consistently improves sustained attention for a novel object, as well as spatial memory. Next, to determine the brain activity correlates of enhanced cognition, we performed EEG/EMG recording while the mice performed the novel object recognition (NOR) task. Power spectral density (PSD) analysis revealed that 3 mg/kg Solriamfetol reduced EEG delta (an index of sleepiness) during exposure to a novel context, and enhanced EEG fast-gamma (an index of mental concentration) during execution of the NOR task. Taken together, our data demonstrate that low-dose Solriamfetol improves memory and attentional performance in wild-type mice.
Research on the roles of multiple social media platforms in the evolution of public events
Authors: Han Ruilian , An Lu , Zhou Wei , Li Gang
Published: January 2025

Purpose

Social media platforms (SMPs) are pivotal in information dissemination and molding public opinion. Various platforms exhibit differences and characteristics. It is necessary to compare and analyze the roles played by different platforms in the evolution of public events.

Design/methodology/approach

This study develops a framework to evaluate the role of SMPs at different stages of public events. To calculate some of these indicators, the GPT-AP-TextRank topic model is constructed. The study further analyzes the correlation between indicators at different stages and SMP’s role and compares SMP’s different roles among the four stages.

Findings

The results reveal significant disparities in the role of different SMPs during public events. Weibo demonstrates notable performance during the outbreak, spread and recession stages of the event, exhibiting a strong influence on public event evolution. Bilibili, Douban, Zhihu and Baidu Tieba show relatively ordinary roles. In addition, compared to the spread stage, SMPs exhibit a stronger ability to influence event redirection in the initial stage, which is different from the original assumption of the study.

Practical implications

The findings expose the powerful roles of SMPs in event evolution, providing valuable insights for enhancing public event governance.

Originality/value

This study proposes an evaluation method for SMPs’ role and introduces a novel GPT-AP-TextRank topic generation model for the indicator calculation.
The differential roles of transient and chronic loneliness in consumers’ variety­ seeking behavior
Authors: Li Ting , Wang Fenghua
Published: January 2025

Purpose

This paper aims to examine the effects of both transient and chronic loneliness on consumers’ variety-seeking (VS) behavior and to identify the various underlying mechanisms involved.

Design/methodology/approach

Four studies were adopted to clarify how transient and chronic loneliness affect consumers’ VS behavior.

Findings

Both transient and chronic loneliness promote consumers’ VS behavior. More importantly, the effect of transient loneliness on VS behavior is driven by perceived loss of control, whereas the effect of chronic loneliness on VS behavior is driven by need for uniqueness and sensation-seeking.

Research limitations/implications

To the best of the authors’ knowledge, this research is the first to explore the differential roles of transient and chronic loneliness on VS behavior, which may open new avenues for future research. First, future research could investigate moderators that influence the impacts of transient and chronic loneliness on VS behavior. Second, future research could examine different participant populations and use cognitive neuroscience techniques to further verify the differential roles of these two types of loneliness on VS behavior.

Practical implications

This research contributes to marketing practice by providing practical guidance on how to effectively design different marketing strategies to promote VS for consumers with different types of loneliness. For consumers with transient loneliness, marketers can benefit from a concerted focus on improving consumers’ sense of control. Yet, for consumers with chronic loneliness, marketing strategies that improve consumers’ need for uniqueness will be more effective.

Originality/value

This research contributes to the literature on loneliness and consumer behavior, which has largely overlooked the distinct roles of different types of loneliness (i.e. transient vs chronic loneliness) in influencing consumer behavior. Specifically, this paper conducted a comparative analysis of the impacts of transient and chronic loneliness on consumers’ VS behavior and proposed that transient and chronic loneliness promote consumers’ VS behavior through divergent underlying mechanisms.
Do firms with more powerful CEOs and greater visibility have better social reputation?
Authors: Kuzey Cemil , Uyar Ali , Al-Shaer Habiba , Karaman Abdullah S.
Published: January 2025

Purpose

In addition to financial performance, firms are increasingly trying to obtain a social reputation from their corporate social responsibility (CSR) engagement within society due to reputational benefits. Thus, the authors seek to highlight two facilitators of social reputation which may help firms realize their targets. Hence, drawing on the signaling, stewardship and legitimacy theories, this study aims to investigate whether chief executive officer (CEO) power and firm visibility help translate CSR engagement into greater social reputation, proxied by CSR awarding.

Design/methodology/approach

Adopting a cross-country and cross-industry sample of 52,549 observations between 2002 and 2021, the authors run a fixed effects regression analysis.

Findings

The authors found that greater CSR engagement leads to better social reputation. Furthermore, CEO power and greater firm visibility foster a positive association between CSR engagement and social reputation. The results are robust to endogeneity concerns, which were addressed by propensity score matching, entropy balancing, instrumental variable regression analysis, alternative samples and regulatory changes.

Practical implications

Although the CEOs’ power is severely criticized in the corporate governance literature due to its weakening effect on board monitoring ability, the authors found that it is beneficial for firms seeking to improve their social reputation. This outcome may help firms shape their upper management structure for greater social reputation gains from CSR engagement. Furthermore, more visible firms achieve greater social reputation through their CSR engagement, which could help managers co-consider firms’ advertising–CSR awarding engagements and budget their financial resources accordingly.

Originality/value

Increasing the CSR engagement of firms has prompted investigations into how firms may better benefit from this investment. However, despite considerable research interest in the financial return of CSR engagement, the social reputation that firms derive from CSR engagement has not been sufficiently addressed. Thus, the authors examine whether two corporate mechanisms, CEO power and firm visibility, could help firms translate CSR engagement into improved social reputation, proxied by CSR awarding.
Unveiling regulatory effectiveness as a mediator between service quality and consumer satisfaction
Authors: Iqbal Shahzaf , Taib Che Azlan Bin , Razalli Mohd. Rizal
Published: January 2025

Purpose

This study aims to investigate how the service quality provided by distribution companies (DISCOs) impacts consumer satisfaction, focusing on the mediating role of regulatory effectiveness as governed by the National Electric Power Regulatory Authority (NEPRA) in Pakistan’s power sector.

Design/methodology/approach

A quantitative research design was used, with data collected via online surveys from domestic electricity consumers of five DISCOs in Punjab, Pakistan. Data analysis was performed using SPSS-25 and SmartPLS-4 software.

Findings

The results indicate that service quality significantly affects both consumer satisfaction and regulatory effectiveness, with regulatory effectiveness positively mediating the relationship between service quality and consumer satisfaction.

Research limitations/implications

The limitations of this study include a cross-sectional design and multistage sampling, which may introduce bias and inadequately represent diverse demographics. Future research should involve commercial users, use longitudinal designs and adopt mixed methods for deeper insights. Nevertheless, the findings emphasize the mediating role of regulatory effectiveness in linking service quality to consumer satisfaction, highlighting the importance of governance in the electricity sector.

Practical implications

The findings offer valuable insights for policymakers, DISCO managers and regulatory bodies, underscoring the need to enhance service quality and regulatory practices to improve consumer satisfaction. Collaboration between DISCOs and NEPRA is recommended to address inefficiencies and governance issues, focusing on infrastructure development, transparency and accountability to enhance the consumer experience in Pakistan’s electricity sector.

Originality/value

This study contributes to the literature by introducing regulatory effectiveness as a mediator between service quality and consumer satisfaction within the power sector, guided by institutional theory.
The gender gap in the early progression of academic careers: evidence from Italy
Authors: Alfano Vincenzo , Cicatiello Lorenzo , Gaeta Giuseppe Lucio , Pinto Mauro
Published: January 2025

Purpose

This paper contributes to the existing literature on the gender gap in academic career advancement by focusing on the very early stage of the academic career, i.e. the transition from Ph.D. completion to a tenured position.

Design/methodology/approach

Using Italian individual-level data, our econometric analyses estimate the likelihood of holding a tenured position conditional on a set of individual-level covariates.

Findings

Our findings support the idea that women have a lower probability of obtaining a tenured position. Results hold even when research productivity and experience are controlled for.

Originality/value

Our conclusions suggest that there is a significant gender gap in progression through an academic career.
Employee flourishing-at-work: a review and research agenda
Authors: Peethambaran Meera , Naim Mohammad Faraz
Published: January 2025

Purpose

This study aims to identify current trends in flourishing-at-work (FAW) research, highlight significant gaps in the literature and guide future research directions in this important area.

Design/methodology/approach

This study adopts a framework-based systematic literature review (SLR) approach, focusing on established theories, contexts and methods and antecedents, decisions and outcomes framework. The utilization of Web of Science and Scopus databases ensures the inclusion of high-quality, peer-reviewed articles, adhering to the Scientific Procedures and Rationales for Systematic Literature Reviews framework.

Findings

This study found significant gaps in the literature of FAW. The summarized research gaps are reported using the Miles taxonomy of research gaps.

Practical implications

Organizations can enhance employee well-being by addressing identified gaps, implementing tailored practices and fostering supportive cultures.

Originality/value

To the best of the authors’ knowledge, this is the first study to represent the first framework-based SLR on the holistic well-being construct, FAW. Using a rigorous methodology and comprehensive databases, our research offers valuable and unique insights, significantly enhancing the scholarly understanding of FAW.
Performance improvement in milk product manufacturing using supply chain strategies – an empirical investigation
Authors: Singh Prabhjot , Samir Sushant , Kumar Kamal , Singh Jagdeep
Published: January 2025

Purpose

This study has been carried out in dairy product manufacturing industry of Northern India to judge the significance of supply chain strategies viz. cost reduction and optimization strategies toward performance improvement and mediator effect of strength and opportunity between strategies and performance parameters.

Design/methodology/approach

Questionnaire survey has been performed to justify their role toward performance improvement. Structural equation modeling, descriptive statistics, hierarchical regression and clusters and partial least square-structural equation modeling has been applied for ascertain the benefits occurred.

Findings

Results indicated that strength (success factors of strength identified from literature) is the significant mediator than opportunity (success factors) for enhancing performance of organization. Small incremental improvements and 5S activities are highly important cost reduction strategies for enhancing performance of supply chain strategies. Supply chain strategies significantly improve the quality of milk in the industry under study. The customer has got high-quality product after implementing supply chain strategies. Right-time delivery of product is only possible if failure modes are analyzed thoroughly. Reliability of performance parameters is 88% which signifies that high benefits are achieved by implementing cost reduction and cost optimization strategies of supply chain concept. Processing of milk is significantly improved after taking combined effect of processing and delivery of product.

Originality/value

This paper helps both academics and managers to gain a better understanding of this question by considering the role of supply chain strategies implementation practically through a standard procedure.