bluuebunny/crossref_metadata_2025 huggingface dataset:
CCAR1 promotes DNA repair via an unanticipated role in alternative splicing
Authors: Karasu Mehmet E. , Joseph Brian J. , Mironov Aleksei , Schroeder Markus S. , Gvozdenovic Ana , Zavolan Mihaela , Corn Jacob E.
Published: September 2023

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology directed repair (HDR) in the context of ∼18’000 individual gene knockdowns. We focused onCCAR1,a poorly understood gene that we found reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi Anemia pathway.CCAR1loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon inFANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.
Escherichia coliself-organizes developmental rosettes
Authors: Puri Devina , Allison Kyle R.
Published: September 2023

Rosettes are self-organizing, circular multicellular communities that initiate developmental processes, like organogenesis and embryogenesis, in complex organisms. Their formation results from the active repositioning of adhered sister cells and is thought to distinguish multicellular organisms form unicellular ones. Though common in eukaryotes, this multicellular behavior has not been reported in bacteria. In this study, we discovered thatEscherichia coliforms rosettes by active sister cell repositioning. After division, sister cells “fold” to actively align at the 2- and 4-cell stages of clonal division, thereby producing rosettes with characteristic quatrefoil configuration. Analysis revealed folding follows an angular random walk, comprised of ∼1-µm strokes and directional randomization. We further showed that this motion was produced by the flagellum, the extracellular tail whose rotation generates swimming motility. Rosette formation was found to requirede novoflagella synthesis suggesting it must balance the opposing forces ofAg43adhesion and flagellar propulsion. We went on to show that proper rosette formation was developmentally required for subsequent morphogenesis of multicellular chains,rpoSexpression, and formation of hydrostatic clonal-chain biofilms. Moreover, we discovered self-folding rosette-like communities in the standard motility assay, indicating this behavior may be general to hydrostatic environments. This study establishes that self-organization of developmental rosettes is a cross-kingdom multicellular behavior. Our findings indicate the potential of targeting bacterial rosettes to interrupt biofilms or reduce their antibiotic tolerance.
A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution
Authors: Nardone Stefano , Luca Roberto De , Zito Antonino , Klymko Nataliya , Nicoloutsopoulos Dimitris , Amsalem Oren , Brannigan Cory , Resch Jon M. , Jacobs Christopher L. , Pant Deepti , Veregge Molly , Srinivasan Harini , Grippo Ryan M. , Yang Zongfang , Zeidel Mark L. , Andermann Mark L. , Harris Kenneth D. , Tsai Linus T. , Arrigoni Elda , Verstegen Anne M. J. , Saper Clifford B. , Lowell Bradford B.
Published: September 2023

The “dorsal pons”, or “dorsal pontine tegmentum” (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled ∼1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed many neuronal subtypes’ unique marker genes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this study’s translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard (http://harvard.heavy.ai:6273/) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.
Frequent horizontal chromosome transfer between asexual fungal insect pathogens
Authors: Habig Michael , Grasse Anna V. , Müller Judith , Stukenbrock Eva H. , Leitner Hanna , Cremer Sylvia
Published: September 2023

Entire chromosomes are typically only transmitted vertically from one generation to the next. The horizontal transfer of such chromosomes has long been considered improbable, yet gained recent support in several pathogenic fungi where it may affect the fitness or host specificity. To date, it is unknown how these transfers occur, how common they are and whether they can occur between different species. In this study, we show multiple independent instances of horizontal transfers of the same accessory chromosome between two distinct strains of the asexual entomopathogenic fungusMetarhizium robertsiiduring experimental co-infection of its insect host, the Argentine ant. Notably, only the one chromosome – but no other – was transferred from the donor to the recipient strain. The recipient strain, now harboring the accessory chromosome, exhibited a competitive advantage under certain host conditions. By phylogenetic analysis we further demonstrate that the same accessory chromosome was horizontally transferred in a natural environment betweenM. robertsiiand another congeneric insect pathogen,M. guizhouense. Hence horizontal chromosome transfer is not limited to the observed frequent events within species during experimental infections but also occurs naturally across species. The transferred accessory chromosome contains genes that might be involved in its preferential horizontal transfer, encoding putative histones and histone-modifying enzymes, but also putative virulence factors that may support its establishment. Our study reveals that both intra- and interspecies horizontal transfer of entire chromosomes is more frequent than previously assumed, likely representing a not uncommon mechanism for gene exchange.

Significance Statement

The enormous success of bacterial pathogens has been attributed to their ability to exchange genetic material between one another. Similarly, in eukaryotes, horizontal transfer of genetic material allowed the spread of virulence factors across species. The horizontal transfer of whole chromosomes could be an important pathway for such exchange of genetic material, but little is known about the origin of transferable chromosomes and how frequently they are exchanged. Here, we show that the transfer of accessory chromosomes - chromosomes that are non-essential but may provide fitness benefits - is common during fungal co-infections and is even possible between distant pathogenic species, highlighting the importance of horizontal gene transfer via chromosome transfer also for the evolution and function of eukaryotic pathogens.
Proteome-scale characterisation of motif-based interactome rewiring by disease mutations
Authors: Kliche Johanna , Simonetti Leandro , Krystkowiak Izabella , Kuss Hanna , Diallo Marcel , Rask Emma , Nilsson Jakob , Davey Norman E. , Ivarsson Ylva
Published: September 2023

Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in the intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ∼57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variant associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular assays, the effects of motif-disruptive mutations were validated, including loss of a nuclear localisation signal in the cell division control protein CDC45 by a mutation associated with Meier-Gorlin syndrome. The study provides insights into how disease-associated mutations may perturb and rewire the motif-based interactome.
Subcortical volumes, frontal cortical thickness, and pro-inflammatory cytokines in schizophrenia versus methamphetamine-induced psychosis
Authors: Blake Lauren , Williams Kimberley Clare , Uhlmann Anne Alex , Temmingh Henk , Burger Antoinette , Stein Dan Joseph , Naudé Petrus J. W.
Published: September 2023

Background and Hypothesis

Clinical features of schizophrenia and methamphetamine-induced psychosis (MAP) have significant overlap. Schizophrenia is associated with alterations in subcortical volumes and cortical thickness and pro-inflammatory cytokines, that may correlate with clinical features. However, analogous work on MAP is lacking. We hypothesise decreased frontal cortical thickness, amygdala and hippocampal volumes in schizophrenia and MAP compared to controls, with increased basal ganglia in schizophrenia compared to MAP.

Study Design

Participants included n=36 schizophrenia, n=27 MAP and 32 age- and sex-matched healthy controls. Diagnosis and symptom severity were determined with the Structured Clinical Interview for Axis I Disorders, and the Positive and Negative Syndrome Scale, respectively. Structural T1-weighted images were acquired using a 3-Tesla magnetic resonance imaging scanner. Serum peripheral cytokine concentrations were measured using a multiplex bead array.

Study Results

Schizophrenia and MAP participants showed decreased left amygdala volumes and frontal cortical thickness compared to controls. Schizophrenia participants had increased bilateral caudate, putamen, and nucleus accumbens (NAcc) volumes compared to controls, and greater right globus pallidus and NAcc volumes compared to MAP. Decreased left amygdala volumes and frontal cortical thickness were significantly associated with longer illness duration in schizophrenia and methamphetamine use in MAP. No significant differences were found in cytokine levels between groups or associations with neuroimaging measures.

Conclusions

This study highlights overlaps and differences in the psychobiology of schizophrenia and MAP.The novel discovery of increased globus pallidus and NAcc volumes in schizophrenia compared with MAP may show important distinctions in the neurobiology between these two conditions.
Convergent evolution of (βα)8-barrel fold methylene-tetrahydropterin reductases utilizing a common catalytic mechanism
Authors: Gehl Manuel , Demmer Ulrike , Ermler Ulrich , Shima Seigo
Published: September 2023

Methylene-tetrahydropterin reductases are folded in (βα)8barrel and catalyze the reduction of a methylene to a methyl group bound to a reduced pterin as C1carrier in various one-carbon (C1) metabolisms. F420-dependent methylene-tetrahydromethanopterin (methylene-H4MPT) reductase (Mer) and the flavin-independent methylene-tetrahydrofolate (methylene-H4F) reductase (Mfr) use a ternary complex mechanism for the direct transfer of a hydride from F420H2and NAD(P)H to the respective methylene group, whereas FAD-dependent methylene-H4F reductase (MTHFR) uses FAD as prosthetic group and a ping-pong mechanism to catalyze the reduction of methylene-H4F. A ternary complex structure of MTHFR is available and based on this structure, a catalytic mechanism was proposed, while no ternary complex structures of Mfr or Mer are reported. Here, Mer fromMethanocaldococcus jannaschii(jMer) was heterologously produced and the crystal structures of the enzyme with and without F420were determined. A ternary complex of jMer was modeled using a functional alignment approach based on the ternary complex structure of MTHFR and the modeled ternary complex of Mfr. Mutational analysis at the structurally conserved positions of the three reductases indicated that although these reductases share a limited sequence identity, the key catalytic glutamate residue is conserved and a common catalytic mechanism involving the formation of a 5-iminium cation of the methylene-tetrahydropterin intermediate is shared. A phylogenetic analysis indicated that the three reductases do not share one common ancestor and the conserved active site structures of the three reductases may be the result of convergent evolution.

STATEMENT

This work provides evidence for a common catalytic mechanism of the functional class of methylene-tetrahydropterin reductases. Despite their very low sequence identity, they share a (βα)8-barrel structure with a similar active site geometry. Phylogenetic and mutational analyses suggested that these enzymes have developed from distinct ancestors as a result of convergent evolution. This work describes an example of a catalytic mechanism that emerged independently for several times during evolution in the three domains of life.
Detection of idiosyncratic gaze fingerprint signatures in humans
Authors: Crockford Sarah K. , Satta Eleonora , Severino Ines , Fiacchino Donatella , Vitale Andrea , Bertelsen Natasha , Busuoli Elena Maria , Mandelli Veronica , Lombardo Michael V.
Published: September 2023

Variation in human gaze can be explained by a variety of factors. Within an individual, gaze patterns can be quite reliable and can be explained in part by heritable common genetic mechanisms. If individual gaze patterns are strongly idiosyncratic, could they enable highly accurate detection of individuals via a ‘gaze fingerprint’? And are gaze fingerprints linked to variation in phenotypes such as autistic traits, which are underpinned by heritable common genetic mechanisms and cause atypical and idiosyncratic gaze to manifest in early development? To answer these questions we utilized a stimulus-rich design where participants viewed 700 stimuli of complex natural scenes, repeated in two sessions separated by ∼1-2 weeks. Across independent discovery (n=105) and replication (n=46) datasets, we find that gaze fingerprinting occurs at high rates (52-63%) relative to chance (1-2%) when gaze similarity is averaged across stimuli. However, such averaging procedures hide a unique non-random individuating code represented as a multivariate ‘gaze fingerprint barcode’ pattern across all 700 stimuli. Within such barcodes, around 91-95% of all individuals had fingerprintable stimuli counts that were significantly higher than situations where identity is randomly permuted. Data-driven clustering of such barcodes results in each individual as its own unique cluster. Finally, increased ‘gaze fingerprintability’ is associated with decreased levels of autistic traits. Overall, this work showcases strong potential for gaze fingerprinting on large-scale data as well as potential translational relevance to conditions such as autism.
Decrypting the functional design of unmodified translation elongation factor P
Authors: Tomasiunaite Urte , Kielkowski Pavel , Krafczyk Ralph , Forné Ignasi , Imhof Axel , Jung Kirsten
Published: September 2023

Stalling of ribosomes during polypeptide synthesis due to consecutive proline motifs is a challenge faced by organisms across all kingdoms. To overcome this, bacteria employ translation elongation factor P (EF-P), while archaea and eukaryotes rely on a/eIF5A. Typically, these elongation factors become active only after undergoing post-translational modifications (PTMs) such as ß-lysinylation, (deoxy-)hypusinylation, rhamnosylation, or 5-aminopentanolyation. An exception to this rule is found in EF-P members of the PGKGP-subfamily, which remain unmodified. However, the mechanism behind the ability of certain bacteria to avoid metabolically and energetically costly PTMs, while retaining active EF-P, remains unclear. In this study, we investigated the design principles governing the full functionality of unmodified EF-Ps inEscherichia coli.We first screened for naturally unmodified EF-Ps that are active in anE. colireporter strain. We identified EF-P fromRhodomicrobium vannieliicapable of rescuing the growth deficiencies and changes in the proteome of anE. coliΔepmAmutant lacking the gene for the modifying EF-P-(R)-ß-lysine ligase. We then identified specific amino acids in domain I of the unmodified EF-P variant that affected its activity. Ultimately, we transferred these functional properties to other marginally active members of the PGKGP EF-P subfamily, resulting in fully functional unmodified variants inE. coli. These results have implications for the improved heterologous expression of polyproline-containing proteins inE. coliand offer applications in other bacterial hosts. Understanding the mechanisms that underlie the functionality of unmodified EF-P provides insights into cellular adaptations to optimize protein synthesis.
Depleting glioblastoma cells of very long-chain acyl-CoA synthetase 3 (ACSVL3) produces metabolic alterations in non-lipid pathways
Authors: Kolar Elizabeth A. , Shi Xiaohai , Clay Emily M. , Liu Yanqiu , Xia Shuli , Zhang Cissy , Le Anne , Watkins Paul A.
Published: September 2023

Knockout (KO) of the fatty acid-activation enzyme very long-chain acyl-CoA synthetase 3 (ACSVL3; SLC27A3) in U87MG glioblastoma cells reduced their malignant growth properties both in vitro and in xenografts. These U87-KO glioma cells grew at a slower rate, became adherence-dependent, and were less invasive than parental U87 cells. U87-KO cells produced fewer, slower-growing subcutaneous and intracranial tumors when implanted in NOD-SCID mice. Thus, depleting U87MG cells of ACSVL3 restored these cells to a phenotype more like that of normal astrocytes. To understand the mechanisms underlying these beneficial changes, we investigated several possibilities, including the effects of ACSVL3 depletion on carbohydrate metabolism. Proteomic and metabolomic profiling indicated that ACSVL3 KO produced changes in glucose and energy metabolism. Even though protein levels of glucose transporters GLUT1 and GLUT3 were reduced by KO, cellular uptake of labeled 2-deoxyglucose was unaffected. Glucose oxidation to CO2was reduced nearly 7-fold by ACSVL3 depletion, and the cellular glucose level was 25% higher in KO cells. Glycolytic enzymes were upregulated by KO, but metabolic intermediates were essentially unchanged. Surprisingly, lactate production and the levels of lactate dehydrogenase isozymes LDHA and LDHB were elevated by ACSVL3 KO. The activity of the pentose phosphate pathway was found to be lower in KO cells. Citric acid cycle enzymes, electron transport chain complexes, and ATP synthase protein levels were all reduced by ACSVL3 depletion. Mitochondria were elongated in KO cells, but had a more punctate morphology in U87 cells. The mitochondrial potential was unaffected by lack of ACSVL3. We conclude that the beneficial effects of ACSVL3 depletion in human glioblastoma cells may result in part from alterations in diverse metabolic processes that are not directly related to role(s) of this enzyme in fatty acid and/or lipid metabolism. (Supported by NIH 5R01NS062043 and KKI institutional funds.)
Histone acetylation in an Alzheimer’s disease cell model promotes homeostatic amyloid-reducing pathways
Authors: Xu Daniel C. , Sas-Nowosielska Hanna , Donahue Greg , Huang Hua , Pourshafie Naemeh , Good Charly R. , Berger Shelley L.
Published: September 2023

Alzheimer’s Disease (AD) is a disorder characterized by cognitive decline, neurodegeneration, and accumulation of amyloid plaques and tau neurofibrillary tangles in the brain. Dysregulation of epigenetic histone modifications may lead to expression of transcriptional programs that play a role either in protecting against disease genesis or in worsening of disease pathology. One such histone modification, acetylation of histone H3 lysine residue 27 (H3K27ac), is primarily localized to genomic enhancer regions and promotes active gene transcription. We previously discovered H3K27ac to be more abundant in AD patient brain tissue compared to the brains of age-matched non-demented controls. In this study, we use iPSC-neurons derived from familial AD patients with an amyloid precursor protein (APP) duplication (APPDupneurons) as a model to study the functional effect of lowering CBP/P300 enzymes that catalyze H3K27ac primarily at gene enhancers. We found that homeostatic amyloid-reducing genes were upregulated in the APPDupneurons compared to non- demented controls. We lowered CBP/P300 to reduce H3K27ac, which led to decreased expression of numerous of these homeostatic amyloid-reducing genes, along with increased extracellular secretion of a toxic amyloid-β species, Aβ(1-42). Our findings suggest that epigenomic histone acetylation, including H3K27ac, drives expression of compensatory genetic programs in response to AD-associated insults, specifically those resulting from APP duplication, and thus may play a role in mitigating AD pathology in neurons.
Parallel pathways carrying direction and orientation selective retinal signals to layer 4 of mouse visual cortex
Authors: Wang Helen , Dey Oyshi , Lagos Willian N. , Behnam Noor , Callaway Edward M. , Stafford Benjamin K.
Published: September 2023

Parallel functional and anatomical visual pathways from the retina to primary visual cortex (V1) via the lateral geniculate nucleus (LGN) are common to many mammalian species, including mice, carnivores and primates. However, the much larger number of retinal ganglion cell (RGC) types that project to the LGN, as well as the more limited lamination of both the LGN and the thalamocortical-recipient layer 4 (L4) in mice, leaves considerable uncertainty about which visual features present in both retina and V1 might be inherited from parallel pathways versus extracted by V1 circuits in the mouse visual system. Here, we explored the relationships between functional properties of L4 V1 neurons and their RGC inputs by taking advantage of two Cre-expressing mouse lines — Nr5a1-Cre and Scnn1a-Tg3-Cre — that each label functionally and anatomically distinct populations of L4 neurons. Visual tuning properties of L4 V1 neurons were evaluated using Cre-dependent expression of GCaMP6s followed by 2-photon calcium imaging. RGCs providing input to these neurons (via LGN) were labeled and characterized using Cre-dependent trans-synaptic retrograde labeling with G-deleted rabies virus. We find significant differences in the tuning of Nr5a1-Cre versus Scnn1a-Tg3-Cre neurons for direction, orientation, spatial frequency, temporal frequency, and speed. Strikingly, a subset of the RGCs had tuning properties that matched the direction and orientation tuning properties of the L4 V1 neurons to which they provided input. Altogether, these results suggest that direction and orientation tuning of V1 neurons may be at least partly inherited from parallel pathways originating in the retina.
Connecting self-report and instrumental behavior during incubation of food craving in humans
Authors: Ruiz Nicholas A , Eckardt Devlin , Briand Lisa A , Wimmer Mathieu , Murty Vishnu P
Published: September 2023

Incubation of craving is a phenomenon describing the intensification of craving for a reward over extended periods of abstinence from reinforcement. Animal models employ instrumental markers of craving to reward cues to examine incubation, while homologous human paradigms often rely on subjective self-reports. Here, we characterize a novel human paradigm that showed strong positive relationships between self-reports and instrumental markers of craving. Further, both measures expressed non-linear relationships with time since last consumption, which parallels homologous animal paradigms of incubation of craving.
Structural basis for peroxidase encapsulation in a protein nanocompartment
Authors: Jones Jesse A. , Andreas Michael P. , Giessen Tobias W.
Published: September 2023

Encapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogenKlebsiella pneumoniae. By combining cryo-electron microscopy with TP mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications.
Where the present gets remembered: Sensory regions communicate with the brain over the longest timescales
Authors: Cooper Greg , Blackburne George , Dekker Tessa , Das Ravi K , Skipper Jeremy I
Published: September 2023

In natural contexts, the brain simultaneously processes sensory information over diverse timescales. Here we reveal how this is reflected in the organisation of asynchronous connectivity in the brain. In 86 individuals watching feature-length movies during functional neuroimaging, we calculated the delay at peak connectivity between brain regions. We found the longest delays in received whole-brain functional connectivity within ‘sensory’ regions (:S 18 seconds). Two complementary dimensionality reduction approaches were used to probe the spatial organisation of connection delays and weights. First, clustering of received delays separated sensory, and transmodal/associative outputting regions, suggesting that putatively localised functions are associated with asynchronous local-to-whole-brain connectivity patterns. Next, we organised delayed connectivity maps by likeness, unveiling five orthogonal gradients of variation, each demonstrating associations between early-sensory and transmodal/associative regions. Together, these findings challenge contemporary conceptualisations of the brain’s temporal hierarchy by emphasising the role of sensory regions as sites of integration across timescales.
WEE1 kinase inhibition triggers severe chromosome pulverization in aneuploid cells
Authors: Haykal Maria M. , Rodrigues-Ferreira Sylvie , Nahmias Clara
Published: September 2023

Aneuploidy, a hallmark of cancer, is a prominent feature associated with poor prognosis in breast cancer. Here, we screened a panel of cell cycle kinase inhibitors to identify novel targets for highly aneuploid breast cancers. We show that increasing aneuploidy in breast cancer cells sensitizes to the inhibition of WEE1 kinase. Upon exposure to WEE1 inhibitor, aneuploid cells exhibit aberrant mitosis characterized by the detachment of centromere proteins from centromeric DNA and pulverization of chromosomes. The occurrence of such phenotype is driven by excessive levels of replication stress and DNA damage during S-phase, that in turn trigger major defects in the subsequent mitosis. We show that DNA2 helicase/nuclease, that regulates replication of centromeric DNA, is the key player responsible for severe chromosome pulverization in mitosis. The heightened vulnerability of aneuploid cells to WEE1 inhibition, coupled with underlying molecular mechanisms, provides a rationale for clinical exploration of WEE1-targeted therapies against aneuploid breast cancers.

Impact Statement

Increased vulnerability of aneuploid cells to WEE1 inhibition is orchestrated by the DNA2 nuclease/helicase. These findings open new therapeutic strategies in the context of personalized medicine in breast cancer.
Targeted memory reactivation during slow-wave sleep vs. sleep stage N2: no significant differences in a vocabulary task
Authors: Wick Anna , Rasch Björn
Published: September 2023

Sleep supports memory consolidation, and slow-wave sleep (SWS) in particular is assumed to benefit the consolidation of verbal learning material. Re-exposure to previously learned words during SWS with a technique known as targeted memory reactivation (TMR) consistently benefits memory. However, TMR has also been successfully applied during sleep stage N2, though a direct comparison between words selectively reactivated during SWS versus N2 is still missing. Here, we directly compared the effects of N2 TMR and SWS TMR on memory performance in a vocabulary learning task in a within-subject design. Thirty-four healthy young participants (21 in the main sample and 13 in an additional sample) learned 120 Dutch–German word pairs before sleep. Participants in the main sample slept for ∼8 h during the night, while participants in the additional sample slept ∼3 h. We reactivated the Dutch words selectively during N2 and SWS in one single night. Forty words were not cued. Participants in the main sample recalled the German translations of the Dutch words after sleep in the morning, while those in the additional sample did so at 2:00 a.m. As expected, we observed no differences in recall performance between words reactivated during N2 and SWS. However, we failed to find an overall memory benefit of reactivated over nonreactivated words. Detailed time–frequency analyses showed that words played during N2 elicited stronger characteristic oscillatory responses in several frequency bands, including spindle and theta frequencies, compared with SWS. These oscillatory responses did not vary with the memory strengths of individual words. Our results question the robustness and replicability of the TMR benefit on memory using our Dutch vocabulary learning task. We discuss potential boundary conditions for vocabulary reactivation paradigms and, most importantly, see the need for further replication studies, ideally including multiple laboratories and larger sample sizes.
The influence of encoding strategy on associative memory consolidation across wake and sleep
Authors: Denis Dan , Bottary Ryan , Cunningham Tony J. , Tcheukado Mario-Cyriac , Payne Jessica D.
Published: September 2023

Sleep benefits memory consolidation. However, factors present at initial encoding may moderate this effect. Here, we examined the role that encoding strategy plays in subsequent memory consolidation during sleep. Eighty-nine participants encoded pairs of words using two different strategies. Each participant encoded half of the word pairs using an integrative visualization technique, where the two items were imagined in an integrated scene. The other half were encoded nonintegratively, with each word pair item visualized separately. Memory was tested before and after a period of nocturnal sleep (N= 47) or daytime wake (N= 42) via cued recall tests. Immediate memory performance was significantly better for word pairs encoded using the integrative strategy compared with the nonintegrative strategy (P< 0.001). When looking at the change in recall across the delay, there was significantly less forgetting of integrated word pairs across a night of sleep compared with a day spent awake (P< 0.001), with no significant difference in the nonintegrated pairs (P= 0.19). This finding was driven by more forgetting of integrated compared with not-integrated pairs across the wake delay (P< 0.001), whereas forgetting was equivalent across the sleep delay (P= 0.26). Together, these results show that the strategy engaged in during encoding impacts both the immediate retention of memories and their subsequent consolidation across sleep and wake intervals.
Mediating effect of ESG performance on executive incentive compensation-financial performance relationship: evidence from MENA banking sector
Authors: Ben Ali Abdelhakim , Chouaibi Jamel
Published: September 2023

Purpose

This study aims to investigate whether integrating environmental, social and governance (ESG) practices mediates the relationship between executive incentive compensation and the financial performance of Islamic and conventional banks in the Middle East and North Africa (MENA) region.

Design/methodology/approach

This study used multiple regression models to analyze the effectiveness of ESG practices as a mediating variable in explaining the relationship between executive incentive compensation and banks’ financial performance between 2015 and 2021. The sample consisted of 57 Islamic and conventional banks operating in the MENA region, and the data were collected from the Thomson Reuters database (Data Stream).

Findings

This research paper showed the positive and significant mediating effect of the ESG practice on Banks’ financial performance. Thus, banks’ financial and stock market profitability is influenced by ESG information disclosure. This finding shows that taking ESG into account improves the relationship between executive incentive compensation and banks’ financial performance.

Practical implications

The results may interest academic researchers, regulators and policymakers and would support stakeholders and decision-makers who wish to discover how executive incentive compensation affects financial performance in banks.

Originality/value

This study contributes to previous literature by studying the mediating effect of ESG practices on the relationship between executive incentive compensation and banks’ financial performance. Indeed, the originality of this research paper is justified by the scarcity of studies and, to the best of the authors’ knowledge, constitutes one of the first attempts to examine this relationship via a mediating variable, i.e. ESG.
Culture and technology in digital transformations: how large companies could renew and change into ecosystem businesses
Authors: Steiber Annika , Alvarez Don
Published: September 2023

Purpose

The purpose and theoretical contributions of this paper are to improve current knowledge on culture's role in firms' digital transformation, as well as to identify and add a cultural “digital maturity” lens to well-known, already actionable frameworks for the digital transformation of firms.

Design/methodology/approach

To increase current knowledge on culture's role in firms' digital transformation, as well as to identify and add a cultural “digital maturity” lens to well-known and actionable frameworks for the digital transformation of firms, a multi-step approach was chosen, including both literature reviews as well as a qualitative study of one company case.

Findings

Early generations of digital transformation frameworks, mainly from the field of information systems (IS), did not take into consideration firms' culture. More recent research in the fields of management and organization, however, emphasizes the role of culture and key cultural attributes favorable for a digital transformation. By integrating key findings on digital transformation from these research fields, a multi-disciplinary framework could be presented, allowing any organization to plan, organize and monitor a digital transformation from three essential lenses: technical (processes and actions for transforming), social (transformation of norms and behavior) and macro (transformation of the perception of the outside world).

Research limitations/implications

Only one case study was included in this study. The developed multi-disciplinary framework needs to be tested in more cases.

Practical implications

Practitioners can use the new integrated framework above for evaluating the conditions for, and the progression of a digital transformation, by using the developed framework and by applying the three lenses.

Social implications

Originality/value

The paper contributes a new multi-disciplinary integrated framework for the digital transformation of enterprises and a further understanding of the impact of culture in the transformation of the firm.
A comprehensive review of environmental, sustainability and climate change curriculum in Taiwan’s higher education institutions
Authors: Liu John Chung-En , Kan Ting-Yu
Published: September 2023

Purpose

This study aims to evaluate the current situation of education for sustainable development, climate change education and environmental education in a nationwide context. Methodologically, this study calls for more research to go beyond case studies and take a similar approach to examine university curricula and facilitate cross-country comparisons.

Design/methodology/approach

This paper examines the status of climate and sustainability curricula in Taiwan’s higher education system. Using the course catalog for the 2020–2021 academic year, the authors constructed a unique data set that includes 1,827 courses at 29 major universities in Taiwan. In each institution, the authors search for course titles that include “climate,” “sustainable/sustainability” and “environment/environmental” as keywords and code the courses according to their disciplines.

Findings

The finding highlights the variations across institutional types and subject matters. Public universities have an average of 4.94 related courses per 1,000 students, whereas private universities have only 3.13. In general, the relevant courses are more concentrated in the STEM and bioscience fields. The curricula, however, are seriously constrained by the disciplinary structure and foster few transdisciplinary perspectives.

Originality/value

The authors seek to go beyond case studies and offer one of the most comprehensive curricula samples at the national level. Taiwan adds an important data point, as the current literature focuses heavily on the USA and Europe.
B2B supply chain risk measurement systems: a SCOR perspective
Authors: Guillot Romane , Dubey Rameshwar , Kumari Sushma
Published: September 2023

Purpose

Globalisation, trade barriers, unprecedented health crises and geo-political crises have forced organisations to revisit their performance measurement systems (PMS) to better prepare their supply chain against the risk and improve performance in times of crisis. This study aims to review the supply chain operation reference (SCOR)-based PMS and propose a dynamic SCOR-based PMS for supply chain risk management (SCRM).

Design/methodology/approach

Due to the need for multi-stakeholder perspectives on SCOR-based PMS for the SCRM, the authors aimed to develop a theory rather than to elaborate upon or test the theory. Hence, the authors adopted an inductive theory-building approach to build research propositions. The authors also gathered 12 semi-structured interviews with knowledgeable managers from B2B international companies.

Findings

The findings of the study highlight the challenges faced by the organisations during the implementation of the SCOR-based performance indicators and the positive impacts they have on decision-making and on the continuous improvement strategy of organisations to tackle supply chain risks and improve performance. The findings suggest that the effects of these indicators are more felt during risk management and risk monitoring stages.

Research limitations/implications

Like any other study, this study has some rules, and, thus, the authors caution the readers that they must interpret the findings of the research considering these limitations. The study is based on semi-structured qualitative interviews. The interviews were conducted with 12 knowledgeable managers from France; thus, the insights drawn from the study cannot be generalised to other settings. Furthermore, the samples represent something other than small and medium enterprises. In the future, the samples from small and medium firms can offer a nuanced understanding of the performance indicators for SCRM.

Originality/value

To the best of the authors’ knowledge, this is one of the few studies which has attempted to revisit the SCOR-based PMS in the B2B supply chain for risk management. The study’s findings help expand the SCOR-based PMS literature and offer numerous insights to the management and consultants facing challenges in SCOR implementation.
CSR employer branding, organisational identification, person–organisation fit and employee retention: a dual mediation model
Authors: Bharadwaj Shubhangi
Published: September 2023

Purpose

Corporate social responsibility (CSR) is gaining recognition and value among researchers, academicians and business professionals. Drawing on theories of social identity and person–organisation fit, the present research propounds a model that investigates the role of CSR branding in influencing employee retention.

Design/methodology/approach

The paper is based on primary survey data from 348 employees working in organisations in the Indian industrial hubs. The study uses the regression and PROCESS macro model to analyse relationship among study variables.

Findings

The study indicated how CSR initiatives could help organisations handle the threat of high turnover storm all over the world, thereby retaining the employees with a high set of skills. Moreover, the paper connotes that employee retention is influenced directly by CSR branding as well as indirectly under the presence of organisational identification and person–organisation fit (mediators).

Practical implications

Results suggest the role of a positive identity and a mutual fit as significant predictors of employee retention. The implications for future research on CSR, employees' stay intentions, employees' identification and value congruence are further discussed in light of the findings.

Originality/value

The novelty of this research insists on shedding light on the indirect mechanisms linking CSR to employee retention that has been overlooked so far, particularly in the Indian setting; studies on an integrated model of organisational identification and person–organisation fit are limited.
Leadership, trustworthiness and employee engagement: an insight during the COVID-19
Authors: Iddagoda Anuradha , Dissanayake Hiranya , Bagienska Anna
Published: September 2023

Purpose

The purpose of this study is to explore the associations between leadership, trustworthiness, and employee engagement during COVID-19.

Design/methodology/approach

In this cross-sectional, quantitative study, surveys of Sri Lankan male and female managers were conducted via standardized questionnaires. The sample size was 297 respondents. The Smart-PLS version 3.36 structural equation model analyzed the data set.

Findings

Both leadership and employee engagement and trustworthiness and employee engagement were found to have a statistically significant relationship. It has been found that leadership indirectly contributes to a higher degree of employee engagement through increased trustworthiness. According to the findings, employee engagement rises when they have the trustworthiness of the leadership in the virtual environment.

Research limitations/implications

According to the findings of this study, organizations need to introduce rules to improve leadership manager roles in a virtual environment, which can improve trustworthiness and employee engagement. It also suggests that organizations should build trustworthiness between employees and leadership through a positive culture in a virtual environment that can improve employee engagement and organizational performance.

Originality/value

Research on leadership and trustworthiness improves employee engagement in a virtual environment is the contribution of this study.
Motivating public health emergency preparedness cooperative behaviors: based on the expectancy disconfirmation model
Authors: Hong Yuxiang , Zhao Jiaqing , Zhang Yue , Su Qiang
Published: September 2023

Purpose

In this study, the expectancy disconfirmation model (EDM) was applied to explain the formation of public health emergency preparedness cooperative behavior (EPCB) as well as considering the roles of official media exposure and positive emotions.

Design/methodology/approach

The analysis was based on a sample of 374 respondents collected during the coronavirus (COVID-19) pandemic. A t-test was used to examine the differences in variables by sex, age and educational background. Hypothesis testing was conducted using structural equation modeling. Amos 24.0 and R 4.0.3 were used to analyze the data.

Findings

The results indicated that (1) official media exposure has a positive impact on expectations for and perceived performance of public services, as well as positive emotions; (2) the EDM can be used to explain public satisfaction with government public health services; and (3) public satisfaction and positive emotions have positive effects on EPCB; (4) EDM and positive emotions mediate the relationship between official media exposure and EPCB.

Originality/value

This study provides practical implications for increasing the EPCB from the perspective of risk communication.
Assessment and risk mitigation on halal meat supply chain using fuzzy best-worst method (BWM) and risk mitigation number (RMN)
Authors: Masudin Ilyas , Zuliana Putri Elma , Utama Dana Marsetiya , Restuputri Dian Palupi
Published: September 2023

Purpose

The purpose of this study is to identify the risks that exist in halal meat supply chain activities and to carry out a risk assessment using the fuzzy best-worst method (FBWM) along with mitigating risks using the risk mitigation number (RMN).

Design/methodology/approach

The method used is to collect several literature reviews related to the halal meat supply chain, which has information relevant to the risks of the meat industry in Indonesia. Then, a focus group discussion was held with several experts who play a role in the meat industry in Indonesia, and 33 identified risks were identified in halal meat supply chain activities. The proposed methodology uses FBWM and RMN in conducting risk assessment and mitigation in the meat industry in Indonesia.

Findings

The analysis reveals that priority risk is obtained by using the global weight value on the FBWM, and then risk mitigation is carried out with RMN. Priority mitigation strategies can mitigate some of the risks to the meat industry in Indonesia. The proposed mitigation strategy is designed to be more effective and efficient in preventing risks that can interfere with product halalness in halal meat supply chain activities in the Indonesian meat industry.

Research limitations/implications

The implications of this study highlight the need for collaboration among stakeholders, improved risk assessment methodologies and the expansion of research into other halal supply chains. By addressing these implications, the halal industry can enhance its integrity, consumer confidence and overall contribution to the global market.

Originality/value

This research provides an integrated approach to identifying, analyzing, assessing and mitigating risks to the meat industry in Indonesia.