bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryo-FIB workflow for imaging brain tissue viain situcryo-electron microscopy
Authors: Ning Jiying , Glausier Jill R. , Hsieh Chyongere , Schmelzer Thomas , Buck Silas A. , Franks Jonathan , Hampton Cheri M. , Lewis David A. , Marko Michael , Freyberg Zachary
Published: February 2023

Cryo-electron microscopy (cryo-EM) enables the study of protein complexes, cytoskeletal elements, and organelles in three dimensions without the use of chemical fixation. Most cryo-EM studies focus on vitreously frozen individual cells separated from their native tissue contexts. This reliance on imaging of single cells is primarily due to technical challenges associated with preparing fresh tissue sections at a thinness sufficient for visualization via cryo-EM. Highly heterogenous and specialized tissues, such as brain, are especially affected by this limitation as the cellular, subcellular, and synaptic milieus can significantly vary across neuroanatomical locations. To address this limitation, we established new instrumentation and a workflow that consists of: 1) high-pressure freezing of fresh brain tissue; 2) tissue trimming followed by cryo-focused ion beam milling via the H-bar approach to generate ultrathin lamellae; and 3) cryo-EM imaging. Here, we apply this workflow to visualize the fine ultrastructural details of organelles, as well as cytoskeletal and synaptic elements that comprise the cortical neuropil within fresh, unfixed mouse brain tissue. Moreover, we present initial studies that apply principles of the above workflow to the analysis of postmortem human brain tissue. Overall, our work integrates the strengths of cryo-electron microscopy and tissue-based approaches to produce a generalizable workflow capable of visualizing subcellular structures within complex tissue environments.
Conformational switching and flexibility in cobalamin-dependent methionine synthase studied by small-angle X-ray scattering and cryo-electron microscopy
Authors: Watkins Maxwell B. , Wang Haoyue , Burnim Audrey , Ando Nozomi
Published: February 2023

Cobalamin-dependent methionine synthase (MetH) catalyzes the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate (CH3-H4folate) using the unique chemistry of its cofactor. In doing so, MetH links the cycling ofS-adenosylmethionine with the folate cycle in one-carbon metabolism. Extensive biochemical and structural studies onEscherichia coliMetH have shown that this flexible, multi-domain enzyme adopts two major conformations to prevent a futile cycle of methionine production and consumption. However, as MetH is highly dynamic as well as both a photosensitive and oxygen-sensitive metalloenzyme, it poses special challenges for structural studies, and existing structures have necessarily come from a “divide and conquer” approach. In this study, we investigateE. coliMetH and a thermophilic homolog fromThermus filiformisusing small-angle X-ray scattering (SAXS), single-particle cryo-electron microscopy (cryo-EM), and extensive analysis of the AlphaFold2 database to present the first structural description of MetH in its entirety. Using SAXS, we describe a common resting-state conformation shared by both active and inactive oxidation states of MetH and the roles of CH3-H4folate and flavodoxin in initiating turnover and reactivation. By combining SAXS with a 3.6-Å cryo-EM structure of theT. filiformisMetH, we show that the resting-state conformation consists of a stable arrangement of the catalytic domains that is linked to a highly mobile reactivation domain. Finally, by combining AlphaFold2-guided sequence analysis and our experimental findings, we propose a general model for functional switching in MetH.
TRAF4 is crucial for the propagation of ST2+ memory Th2 cells in IL-33-mediated type 2 airway inflammation
Authors: Xiao Jianxin , Chen Xing , Liu Weiwei , Qian Wen , Bulek Katarzyna , Hong Lingzi , Miller-Little William , Li Xiaoxia , Liu Caini
Published: February 2023

Tumor necrosis factor receptor (TNF)-associated factor 4 (TRAF4) is an important regulator of type 2 responses in the airway; however, the underlying cellular and molecular mechanisms remain elusive. Herein, we generated T cell-specific TRAF4-deficient (CD4cre-Traf4fl/fl) mice and investigated the role of TRAF4 in interleukin (IL)-33 receptor (ST2, suppression of tumorigenicity 2)-expressing memory Th2 cells (ST2+ mTh2) in IL-33-mediated type 2 airway inflammation. We found that in vitro polarized TRAF4-deficient (CD4cre- Traf4fl/fl) ST2+ mTh2 cells exhibited decreased IL-33-induced proliferation as compared with TRAF4-sufficient (Traf4fl/fl) cells. Moreover, CD4cre-Traf4fl/fl mice showed less ST2+ mTh2 cell proliferation and eosinophilic infiltration in the lungs than Traf4fl/fl mice in the preclinical models of IL-33-mediated type 2 airway inflammation. Mechanistically, we discovered that TRAF4 was required for the activation of AKT/mTOR and ERK1/2 signaling pathways as well as the expression of transcription factor Myc and nutrient transporters (Slc2a1, Slc7a1, and Slc7a5), signature genes involved in T cell growth and proliferation, in ST2+ mTh2 cells stimulated by IL-33. Taken together, the current study reveals a previously unappreciated role of TRAF4 in ST2+ mTh2 cells in IL-33-mediated type 2 pulmonary inflammation, opening up avenues for the development of new therapeutic strategies.
Life history and cancer in birds: clutch size predicts cancer
Authors: Kapsetaki Stefania E. , Compton Zachary , Dolan Jordyn , Harris Valerie K. , Rupp Shawn M. , Duke Elizabeth G. , Harrison Tara M. , Aksoy Selin , Giraudeau Mathieu , Vincze Orsolya , McGraw Kevin J. , Aktipis Athena , Tollis Marc , Boddy Amy M. , Maley Carlo C.
Published: February 2023

Cancer is a disease that affects nearly all multicellular life, including birds. However, little is known about what factors explain the variance in cancer prevalence among species. Litter size is positively correlated with cancer prevalence in managed species of mammals, and larger body size, but not incubation or nestling period, is linked to tumor prevalence in wild birds. Also, birds that produce more elaborate sexual traits are expected to have fewer resources for cancer defenses and thus higher cancer prevalence. In this study, we examined whether cancer prevalence is associated with a wide variety of life history traits (clutch size, incubation length, body mass, lifespan, and the extent of sexual dimorphism) across 108 species of managed birds in 25 different zoological facilities, sanctuaries, and veterinary clinics. We found that clutch size was positively correlated with cancer and neoplasia (both benign and malignant) prevalence, even after controlling for body mass. Cancer prevalence was not associated with incubation length, body mass, lifespan, or sexual dimorphism. The positive correlations of clutch size with cancer prevalence and neoplasia prevalence suggest that there may be life-history trade-offs between reproductive investment and somatic maintenance (in the form of cancer prevention mechanisms) in managed birds.
Insecticidal Efficacy of Selected Botanicals on three species of Adult Mosquitoes in Osogbo, Osun State, Nigeria
Authors: Ademodi P.K. , Busari L.O. , Iwalewa Z.O. , Fasasi K.A
Published: February 2023

The present study investigated the insecticidal potency of phytochemicals from three indigenous botanicals namelyMoringa oleifera(Drumstick tree),Vernonia amygdalina(Bitter leaf) andOcimum gratissimum(Scent leaf) against adult mosquitoes of theAnophelesspecies,Aedesspecies andCulexspecies cum their larval habitats.

Collection of the mosquito larval was made after scouting and identifying their breeding sites using scoops, plastic containers, sieves etc. Larva collection was done in the wet season (April to October) while the collected larva were conveyed to the laboratory and reared until they emerged into adults. A bioassay comprising twenty five adult mosquitoes from each of the three adult mosquito species were exposed to the botanicals at three different concentrations (5g/10ml, 10g/10ml and 15g/10ml) to assess their insecticidal potency which was measured through their knockdown rate (kdr) and mortality rate. The kdr were recorded at intervals for an hour while the mortality rates were recorded after 24hours of exposure.

A total of 400 mosquito larva were collected and five larval habitat encountered. The three botanicals showed insecticidal potency against the adult mosquito species. However,O. gratissimumhad the highest potency at 15g/10ml againstAnopheles(46%) andCulex(34%) species respectively (p □ 0.05).Aedes sppwas resistant to the botanicals which may be due to a resistance barrier mechanism inAedes sppthat the botanicals lack the ability to break.

The botanicals could be adopted in the control of adult mosquitoes as they are biodegradable, eco-friendly and economical in contrast to synthetic insecticides with a view to consolidating global efforts on mosquito-borne diseases control and elimination with little or no human or environmental hazard.
Somatotopic organization among parallel sensory pathways that promote a grooming sequence inDrosophila
Authors: Eichler Katharina , Hampel Stefanie , Alejandro-García Adrián , Calle-Schuler Steven A. , Santana-Cruz Alexis , Kmecova Lucia , Blagburn Jonathan M. , Hoopfer Eric D. , Seeds Andrew M.
Published: February 2023

Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered thatDrosophilaperform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on theDrosophilahead that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.
Spatial omics imaging of fresh-frozen tissue and routine FFPE histopathology on a single cancer needle core biopsy: freezing device and multimodal workflow
Authors: Rittel Miriam F. , Schmidt Stefan , Weis Cleo-Aron , Birgin Emrullah , van Marwick Björn , Rädle Matthias , Diehl Steffen J. , Rahbari Nuh , Marx Alexander , Hopf Carsten
Published: February 2023

Complex molecular alterations underlying cancer pathophysiology are intensely studied with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and immuno-histochemistry (IHC) of few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI are emerging diagnostic technologies for identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable and precise methods for preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology on the same biopsy core. As proof-of-concept, we analyzed surgical human liver cancer specimen by IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis on the same biopsy core. This workflow allowed spatial comparison between different spectral profiles and alterations in tissue histology, as well as direct comparison to histological diagnosis without the need of an extra biopsy.

SIMPLE SUMMARY

Routine clinical approaches for cancer diagnosis demand fast, cost-efficient, and reliable methods, and their implementation within clinical settings. Currently, histopathology is the golden standard for tissue-based clinical diagnosis. Recently, spatially resolved molecular profiling techniques like mass spectrometry imaging (MSI) or infrared spectroscopy imaging (IRI) have increasingly contributed to clinical research, e.g., by differentiation of cancer subtypes using molecular fingerprints. However, adoption of the corresponding workflows in clinical routine remains challenging, especially for fresh-frozen tissue specimen. Here, we present a novel device based on 3D-printing technology, which facilitates sample preparation of needle biopsies for correlated clinical tissue analysis. It enables combination of MSI and IRI on fresh-frozen clinical samples with histopathological examination of the same needle core after formalin-fixation and paraffin-embedding (FFPE). This device and workflow can pave the way for a more profound understanding of biomolecular processes in cancer and, thus, aid more accurate diagnosis.

Abstract Figure
IN SITU IMAGING OF RETINAL CALCIUM DYNAMICS IN AWAKE ANIMALS
Authors: Wang Yixiang , Su Ashley , Jin Jialin , Barson Daniel , Crair Michael
Published: February 2023

Mammalian vision starts in the retina. The study of retinal circuitsin vivois essential for comprehending retinal neural dynamics under physiological conditions. While several transpupillary retina imaging techniques have been utilized in anesthetized animals, thein situimaging of retinal activity in awake animals has been more difficult to accomplish. These limits have frustrated crucial scientific inquiries, such as how visual processing in the retina is modulated by behavior. In this study, we present novel experimental approaches that stabilize the eye to accessin situretinal dynamics with optical techniques in awake mice. Our findings demonstrate that this method can be utilized to: 1) image neural activity in distinct cell types across multiple ages, 2) record meso-scale (e.g. spontaneous retinal waves) or cellular retinal dynamics, 3) study retina functional connectivityin vivo, and 4) pharmacologically manipulate retinal activity. We applied these novel approaches to demonstrate that retinal activity is strongly modulated by movement through H1R-dependent histaminergic transmission in vivo, even at the amacrine cell level. These methods are suitable to simultaneously record retinal and brain activity dynamics or to investigate retinal responses to patterned visual stimuli, making accessible fundamental questions about visual processing that have previously been very challenging to achieve.
Integrative analysis ofin vitrostrategies to induce human vascularized cerebral organoids using single-cell RNA sequencing data
Authors: Sato Yuya , Asahi Toru , Kataoka Kosuke
Published: February 2023

Cerebral organoids are three-dimensionalin vitrocultured brains that mimic the function and structure of the human brain. One of the major challenges for cerebral organoids is the lack of functional vasculature. Without perfusable vessels, oxygen and nutrient supplies may be insufficient for long-term culture, hindering the investigation of the neurovascular interactions. Recently, several strategies for the vascularization of human cerebral organoids have been reported. However, the generalizable trends and variability among different strategies are unclear due to the lack of a comprehensive characterization and comparison of these vascularization strategies. In this study, we aimed to explore the effect of different vascularization strategies on the nervous system and vasculature in human cerebral organoids. We integrated single-cell RNA sequencing data of multiple vascularized and vascular organoids and fetal brains from publicly available datasets and assessed the protocol-dependent and culture-day-dependent effects on the cell composition and transcriptomic profiles in neuronal and vascular cells. We revealed the similarities and uniqueness of multiple vascularization strategies and demonstrated the transcriptomic effects of vascular induction on neuronal and mesodermal-like cell populations. Moreover, our data suggested that the interaction between neurons and mesodermal-like cell populations is important for the cerebrovascular-specific profile of endothelial-like cells. This study highlights the current challenges to vascularization strategies in human cerebral organoids and offers a benchmark for the future fabrication of vascularized organoids.
Genomic, genetic and phylogenetic evidence for a new falcon species using chromosome-level genome assembly of the gyrfalcon and population genomics
Authors: Al-Ajli Farooq Omar , Formenti Giulio , Fedrigo Olivier , Tracey Alan , Sims Ying , Howe Kerstin , Al-Karkhi Ikdam M. , Althani Asmaa Ali , Jarvis Erich D. , Rahman Sadequr , Ayub Qasim
Published: February 2023

The taxonomic classification of a falcon population found in the Altai region in Asia has been heavily debated for two centuries and previous studies have been inconclusive, hindering a more informed conservation approach. Here, we generated a chromosome-level gyrfalcon reference genome using the Vertebrate Genomes Project (VGP) assembly pipeline. Using whole genome sequences of 44 falcons from different species and populations, including “Altai” falcons, we analyzed their population structure, admixture patterns and demographic history. We find that the Altai falcons are genomically mosaic of saker and gyrfalcon ancestries, and carry distinct W- and mitochondrial-haplotypes that cluster with the lanner falcon. The Altai haplotype diverged 422,000 years ago from the ancestor of sakers and gyrfalcons, both of which, in turn, split 109,000 years ago. The Altai W chromosome includes coding variants that may influence important structural, behavioral and reproductive traits. These findings support the designation of Altai falcons as a distinct falcon species (Falco altaicus).
Temporal modification of H3K9/14ac and H3K4me3 histone marks mediates mechano-responsive gene expression during the accommodation process in poplar
Authors: Ghosh Ritesh , Roué Juliette , Franchel Jérôme , Paul Amit , Leblanc-Fournier Nathalie
Published: February 2023

Plants can attenuate their molecular response to repetitive mechanical stimulation as a function of their mechanical history. For instance, a single bending of stem is sufficient to attenuate the gene expression in poplar plants to the subsequent mechanical stimulation, and the state of desensitization can last for several days. The role of histone modifications in memory gene expression and modulating plant response to abiotic or biotic signals is well known. However, such information is still lacking to explain the attenuated expression pattern of mechano-responsive genes in plants under repetitive stimulation. Using poplar as a model plant in this study, we first measured the global level of H3K9/14ac and H3K4me3 marks in the bent stem. The result shows that a single mild bending of the stem for 6 seconds is sufficient to alter the global level of the H3K9/14ac mark in poplar, highlighting the fact that plants are extremely sensitive to mechanical signals. Next, we analyzed the temporal dynamics of these two active histone marks at attenuated (PtaZFP2, PtaXET6, andPtaACA13) and non-attenuated (PtaHRD) mechano-responsive loci during the desensitization and resensitization phases. Enrichment of H3K9/14ac and H3K4me3 in the regulatory region of attenuated genes correlates well with their transient expression pattern after the first bending. Moreover, the levels of H3K4me3 correlate well with their expression pattern after the second bending at desensitization (3 days after the first bending) as well as resensitization (5 days after the first bending) phases. On the other hand, H3K9/14ac status correlates only with their attenuated expression pattern at the desensitization phase. The expression efficiency of the attenuated genes was restored after the second bending in the histone deacetylase inhibitor-treated plants. While both histone modifications contribute to the expression of attenuated genes, mechanostimulated expression of the non-attenuatedPtaHRDgene seems to be H3K4me3 dependent.
Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease
Authors: Hurley Miriam E. , White Ed , Sheard Thomas M.D. , Steele Derek , Jayasinghe Izzy
Published: February 2023

Rapid release of calcium from internal stores via ryanodine receptors (RyRs) is one of the fastest types of cytoplasmic second messenger signalling in excitable cells. In the heart, rapid summation of the elementary events of calcium release, calcium sparks, determine the contraction of the myocardium. Recent advances in super-resolution microscopy methods have revealed complex clustering patterns of RyRs at single-channel resolution. Here, we have experimentally correlated sub-sarcolemmal spontaneous calcium sparks in rat right ventricular myocytes with the underlying nanoscale sub-sarcolemmal RyR patterns resolved with super-resolution DNA-PAINT microscopy. Local functional groupings and clustering patterns of RyR were sampled by the location and the two-dimensional area of each calcium spark to reveal a steep dependence of the integral of a calcium spark on the sum of the local RyRs. Visualisation of recurring spark sites showed evidence of repeated and triggered saltatory activation of multiple local RyR clusters. In similar myocytes taken from rats with induced right ventricular failure, RyR clusters themselves showed a dissipated morphology and fragmented (smaller) clusters. The failing myocytes featured greater heterogeneity in both the spark properties and the relationship between the integral of the calcium spark and the local ensemble of RyRs. Whilst fragmented (smaller) RyR clusters were rarely observed to directly underlying the larger sparks or the recurring spark sites, local interrogation of the channel-to-channel distances confirmed a clear link between the positions of each calcium spark and the tight non-random clustering of the local RyRs in both healthy and failing ventricles.
Specific guidelines for time and space of multisensory plasticity in the superior colliculus
Authors: Wang Linghong , Han Yaxin , Sun Zhe , Ouyang Biao , Dong Chao
Published: February 2023

The potential to combine facts from exceptional senses, and thereby facilitate detecting and localizing events, commonly develops regularly in cat superior colliculus (SC) neurons. Multisensory integration in SC neurons depends on the spatial and temporal relationships of cross-modal cues. Here, we reveal that the parallel process of short-term plasticity during adulthood that would adapt multisensory integration to reliable changes in environmental conditions. The short-term experience altered the temporal preferences of SC neurons, this short-term plasticity was limited to changes in cross-modal timing (a factor commonly induced by events at different distances from the receiver. Nonetheless the plasticity was no evident in response to changes in cross-modal spatial configuration.
CVD-associated SNPs with regulatory potential drive pathologic non-coding RNA expression
Authors: Zhu Chaonan , Baumgarten Nina , Wu Meiqian , Wang Yue , Das Arka Provo , Kaur Jaskiran , Ardakani Fatemeh Behjati , Duong Thanh Thuy , Pham Minh Duc , Duda Maria , Dimmeler Stefanie , Yuan Ting , Schulz Marcel H. , Krishnan Jaya
Published: February 2023

Background

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding.

Methods

The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed.

Results

By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs.

Conclusions

IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.
Generation of Bessel beam lattices by a single metasurface for neuronal activity recording in zebrafish larva
Authors: Archetti Anna , Bruzzone Matteo , Tagliabue Giulia , dal Maschio Marco
Published: February 2023

Bessel Beams (BBs) and BB lattices are structured-light excitation profiles frequently applied in material processing, nonlinear spectroscopy and in many fluorescence microscopy methods such as Light Sheet Microscopy (LSM). In LSM, BBs and BB-lattices offer wider excitation profiles, higher acquisition rate, enhanced resolution, and improved signal-to-noise ratio, while reducing the overall phototoxicity. However, this performance improvement typically comes at the cost of layout complexity and spatial constraints, originating from the optical arrangement required for obtaining BB features and for multiplexing the BB in a lattice of beamlets. Here, we introduce a novel method for encoding in a single flat element all the optical operations required to generate a BB lattice, including those of the excitation objective. We assessed the effective capabilities of this approach, using Meta-Surface (MS) technology to fabricate the corresponding flat optical element and to characterize its optical figures. Finally, we demonstrated its actual application in LSM, recording neuronal activity at cellular resolution in the zebrafish larval brain using fluorescence based neuronal activity reporters. In perspective, this approach, applied here for LSM, prompts a step forward in the BB versatility and in the BB application scenarios.
Twainspotting: Identity Revealed During a Simple, but Extended Conversation with a Humpback Whale
Authors: Crutchfield James P. , Jurgens Alexandra M.
Published: February 2023

Extended acoustic interactions with a humpback whale (Megaptera novaeangliae) were captured via human-initiated playbacks of the purported humpback “throp” social call and hydrophone recordings of the animal’s vocalized responses during August 2021 in Frederick Sound, Southeast Alaska. Multivariate statistical analyses performed after the event, that adapted the Wasserstein metric to spectrograms, strongly imply that the played back call was from the same animal, which had been recorded the previous day and initially selected for its clarity. This suggests these interactive playback studies may have formed a probe of time-delayed self-recognition. Fluke photographs taken that previous day and during the interactions revealed that the animal had been identified 38 years earlier, now known as the female humpback named Twain 14 years ago.

This exciting and to our knowledge unique series of interactive vocalization events, while hopeful, poses more questions than answers. Most basically, did the half-hour long series of acoustic exchanges constitute an interspecies conversation? We argue that analysis tools available to infer the implied causality of interaction—statistical dependency, multivariate information theory, and machine learning—leave the question open. That said, and perhaps more importantly, the extended interaction broaches questions whose answers bear directly on future interspecies communication and, more generally, the human appreciation of nonhuman intelligence. The reported human-humpback interactions will facilitate exploring these issues at new depths.
The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc
Authors: Dudek Michal , Morris Honor , Rogers Natalie , Pathiranage Dharshika RJ , Chan Danny , Kadler Karl E , Hoyland Judith , Meng Qing-Jun
Published: February 2023

The circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks which control ∼6% of the transcriptome in a rhythmic manner, including key genes involved in extracellular matrix (ECM) homeostasis. However, it remains largely unknown to what extent the local IVD molecular clock is required to drive rhythmic gene transcription and IVD physiology. In this work, we identified profound age-related changes of ECM microarchitecture and an endochondral ossification-like phenotype in the annulus fibrosus (AF) region of the IVD in theCol2a1-Bmal1knockout mice. Circadian time series RNA-Seq of the whole IVD inBmal1knockout revealed loss of circadian patterns in gene expression, with an unexpected emergence of 12-hour ultradian rhythms, including FOXO transcription factors. Further RNA sequencing of the AF tissue identified region-specific changes in gene expression, evidencing a loss of AF phenotype markers and a dysregulation of ECM and FOXO pathways inBmal1knockout mice. Consistent with an up-regulation of FOXO1 mRNA and protein levels inBmal1knockout IVDs, inhibition of FOXO1 in AF cells suppressed their osteogenic differentiation. Collectively, these data highlight the importance of the local molecular clock mechanism in the maintenance of the cell fate and ECM homeostasis of the IVD. Further studies may identify potential new molecular targets for alleviating IVD degeneration.
When does intellectual capital enhance innovation capability? A three-way interaction test
Authors: Karadag Hande , Sahin Faruk , Bulut Cagri
Published: February 2023

Purpose

In the current study based on the resource-based view (RBV), a three-way interaction model tests the relationships among human and social capital resources, innovation orientation (IO) and innovation capability in the context of new ventures.

Design/methodology/approach

Hierarchical linear regression modeling presents the linear relations at two decision layers of start-ups, their founders and managers. Data is collected and analyzed from 233 new ventures in Turkey.

Findings

Findings of the two and three-way interaction analyses indicate a positive relationship between human capital and innovation capability when social capital and IO are high; however, the relation turns off when low.

Research limitations/implications

The study extends the previous works on the proposed link between intellectual capital (IC) resources and innovation, by confirming the moderating role of social capital and IO on the positive association between human capital resources and innovation capability.

Practical implications

The results show that for start-up companies, the co-existence of strong social capital and the strategic orientation towards innovation is required for the effective utilization of human capital for generating innovation capability within the organization. Thus, this study highlights the importance of networks, alliances and social relationships, together with the unification of strategic thinking, organizational learning and a culture of innovation for attaining innovation goals, which are crucial for the survival and success of these units.

Originality/value

This study presents the first model in the literature which examines the moderating effects of IO and social capital on the human capital-innovation capability relationship.
Collaborative learning in online breakout rooms: the effects of learner attributes on purposeful interpersonal interaction and perceived learning
Authors: Wilkins Stephen , Butt Muhammad Mohsin , Hazzam Joe , Marder Ben
Published: February 2023

Purpose

Breakout rooms are commonly used by lecturers as a means to achieve collaborative learning in online lessons. Although breakout rooms can be effective at encouraging student engagement, interaction and learning, many students dislike being forced to interact with peers, and for some students, it can lead to feelings of anxiety and stress. Successful collaborative learning depends upon having the “right” individuals working together, so the purpose of this research is to identify specific learner attributes that are associated with purposeful interpersonal interaction in breakout rooms.

Design/methodology/approach

An online survey was used to obtain data from 664 higher education students in the USA, which were analyzed using partial least squares structural equation modeling (PLS-SEM).

Findings

Students' technology readiness, social identification and intercultural communication competence are each significantly related to the achievement of purposeful interpersonal interaction, which is strongly related to students' perceived learning.

Practical implications

The findings of this research emphasize the importance of lecturers considering learner attributes when forming breakout room groups.

Originality/value

The breakout room represents a unique and specific context for collaborative learning, where there may be minimal lecturer supervision and where students may choose to disengage by turning off their cameras and microphones or simply listen without participating (known as lurking). The existing literature has given little attention to how lecturers allocate students to online breakout rooms.
The effect of integrated reporting trends on shareholders' fund: does financial leverage matter?
Authors: Haladu Alhassan , Bin-Nashwan Saeed Awadh
Published: February 2023

Purpose

In many societies, environmental problems have had some negative impacts on both social and economic features with issues like capital structure seriously affected. In this write-up, an attempt has been made to pinpoint the influence of the combined effects of integrated reporting and financial leverage on the value of a firm. In most emerging markets, investment is heavily dependent on foreign capital inflow which is mainly in the form of financial leverage. It is, therefore, necessary to know how this shapes the net worth of firms in which they are invested. Shareholders' fund is a major factor in determining the level of investment and economic stability of a nation and consequently improvements in sustainable development. Hence, the moderating role of financial leverage in the integrated reporting-shareholders’ funds relationship aims to warrant this research.

Design/methodology/approach

All listed firms on the Nigerian Stock Exchange (NSE) as of 31st December 2021 were affected by this research. Filtering resulted in the use of 77 companies as a sample for the study covering a period of 12 years (2010–2021) with a total of 788 observations. Analyses of data were done through line graphs to show the trend and flow of disclosures between 2010 and 2021. Furthermore, linear regression was also applied to help determine the multiple effects of financial leverage and integrated reporting on shareholders' funds.

Findings

The outcomes showed that economic disclosure was 100% throughout the period of observation as opposed to environmental and social disclosures which, fluctuate throughout the period with an average of slightly over 55%. It was also discovered that a low but significant financial leverage moderated the interaction of integrated reporting on shareholders' funds.

Practical implications

Stakeholders and policymakers should, therefore, put in place rules, regulations, standards, structures and administrative networks to enable firms to comply with local rules, guidelines and upgraded standards of international worth on sustainability issues.

Originality/value

This research explores the problem of the effects of integrated reporting on investment capital as it affects developing economies. Results from this study could go a long way in narrowing the lack of interest in sustainability issues by prospective investors coupled with the low level of environmental and social reporting by firms in African economies that are mostly underdeveloped.
Helping the police with their inquiries: improving investigator resilience and capacity in England and Wales
Authors: James Adrian , Rogers Colin , Turner James , Silverstone Daniel
Published: February 2023

Purpose

In 2016, the oversight body for policing in England and Wales reported a national shortage of 5,000 qualified detectives and other investigators. Commissioned by the National Police Chiefs Council, this research critically assessed initiatives taken by the Police Service of England and Wales since that time to remedy that shortfall. The purpose of this study is to answer the question, “To what extent can fast-track investigator recruitment and training schemes enhance the PSEW’s investigative capacity and capability?”

Design/methodology/approach

Between 2019 and 2020, the authors examined four cases in England and Wales. Three were novel fast-track programmes for new joiners. The fourth was an investigator resilience programme. This study was qualitative and interpretive in nature. The authors carried out systematic reviews of the literature on investigative policy and detective work. The authors reviewed internal evaluations completed by Forces A, B and C. The authors interviewed respondents (n = 82) and supplemented the interview data with survey data (n = 45; N = 127); the authors analysed the data thematically and reviewed the findings in the context of systems theory and social identity theory.

Findings

The major themes identified by the analysis presented in this study were marketing and recruitment, attrition and progression, acceptance of the trainees, training and trainees’ welfare and well-being. The programmes were not as successful as they might have been because of systems failures. Principally, ineffective coordination of the programmes with other elements of the forces on which their success also relied (such as training, human resources and detective, departments). A critical limiting factor was the lack of experienced, skilled detectives able to train, support and mentor the trainees.

Practical implications

This paper provides empirical evidence of the efficacy of a whole systems approach to organisational change. This study evidences the crisis in police investigative practice that limits the service that the police can provide to victims and communities and ultimately threatens police legitimacy. This study provides insights from police practitioners into detective work in the modern era and highlights areas where improvement is necessary. The research on which this study is based was commissioned by the National Police Chiefs Council. Thus, there is institutional buy in to its findings.

Originality/value

With its roots firmly in empiricism, this paper presents the first scholarly evaluation of the police's attempts to make up a massive shortfall in investigators. To the best of the authors’ knowledge, this paper presents the first attempt to explain the challenges the police faced in this context, thematically. This study’s focus on systems and on human behaviour is intended to inform a wide audience beyond British policing.
How economic globalization affects the ecological footprint in India? A novel dynamic ARDL simulations
Authors: Villanthenkodath Muhammed Ashiq , Pal Shreya
Published: February 2023

Purpose

This study scrutinizes the impact of economic globalization on ecological footprint while endogenizing economic growth and energy consumption during 1990–2018 in India.

Design/methodology/approach

For time series analysis, the standard unit root test has been employed to unveil the integration order. Then, the cointegration was confirmed using autoregressive distributed lag (ARDL) analysis. Further, the study executed the dynamic ARDL simulation model to estimate long-run and short-run results along with simulation and robotic prediction.

Findings

The cointegration analysis confirms the existence of a long-run association among variables. Further, economic globalization reduces the ecological footprint in the long-run. Similarly, energy consumption decreases the ecological footprint. In contrast, economic growth spurs the ecological footprint in India.

Originality/value

The present study makes valuable and original contributions to the literature by applying a multivariate ecological footprint function, assessing the impact of economic globalization on ecological footprint while considering economic growth and energy consumption in India.
Intentions to adopt the blockchain: investigation of the retail supply chain
Authors: Mukherjee Subhodeep , Baral Manish Mohan , Lavanya B. Latha , Nagariya Ramji , Singh Patel Bharat , Chittipaka Venkataiah
Published: February 2023

Purpose

Blockchain can track the material from the manufacturer to the end customers. Therefore, it can ensure the product's authenticity, transparency and trust in the retail supply chain (SC). There is a need to trace and track the retail products before it reaches the customers to check the quality of the products so that expired products can be recycled and reused, which in turn will help gain customers' trust. This research aims to investigate retail employees' behavioural intention to adopt blockchain in the retail SC.

Design/methodology/approach

To examine the behavioural intention of employees in the retail SC, the research uses three theories – the technology acceptance model; the unified theory of acceptance and use of technology; and the theory of planned behaviour. The technology acceptance model measures the employee's acceptance of blockchain in the retail SC. The unified theory of acceptance is used in this research to measure how blockchain adoption will improve the performance of the employees. The theory of planned behaviour is used in this research to measure whether the employees intend to adopt blockchain. A survey was carried out in the retail stores of India. Exploratory factor analysis and structural equation modelling were used for data analysis.

Findings

This study found that the employees of the retail stores have a positive intention and attitude to adopt blockchain technology. Further, it was found that perceived behavioural control and effort expectancy was not promoting blockchain adoption in the retail sector.

Practical implications

This study will help the retail stores' employees understand the blockchain in their operations and will motivate the top management of the retail companies to adopt this technology. The study is limited to the retail SC in India only.

Originality/value

This study uses three theories technology acceptance model; the unified theory of acceptance and use of technology; and the theory of planned behaviour, which were not used in earlier studies of blockchain adoption in the retail SC.
Money pills: corporate political activity effect on mergers and acquisitions
Authors: Beal Partyka Raul , Lana Jeferson , Marcon Rosilene
Published: February 2023

Purpose

This study aims to contribute to the corporate political activities (CPAs) field by suggesting the effect of campaign contributions on the time that firms wait for regulators’ decisions.

Design/methodology/approach

This paper analyzes 358 mergers and acquisitions (M&A) from 2008 to 2017 in Brazil through ordinary least squares regression with robustness control and causal operationalization in a small vote margins treatment.

Findings

Campaign contributions speed up the M&A regulator’s decisions. Campaign contributions amounts proved to be effective in decreasing the waiting time for judgments of M&A deals. Besides, National Development Bank disbursements to companies in M&A deals, served as a moderator to help reduce the waiting time.

Research limitations/implications

The main implication of this paper to the antecedents of CPA research is the estimation of time as an output of the political efforts of firms. Previous research focuses on what firms could get. Here, the authors focus on when. As a limitation, this study analyzes CPA through campaign contributions, as the only reliable source of CPA publicly available. Firms use multiple mechanisms of CPA. It would be expected for new papers to test different CPA mechanisms, such as political connections and lobbying.

Practical implications

This study provides evidence of the use of CPA as a relevant mechanism for firms to avoid institutional risks by getting regulators’ decisions faster. This evidence is useful for firms to grant their competitive advantage in a highly volatile environment, such as an emerging market.

Social implications

What happens in the nonmarket environment interferes within markets. Businesses seek to finance political projects with which they are more aligned, and governments provide capital to businesses in exchange for political support. Whether to expand successfully may also depend on early entrants, who will have acquired enough leadership to dominate the market.

Originality/value

While most of the research on nonmarket strategy focuses on what firms can get as an output for CPA efforts, this study provides here evidence on when firms can get it. As one can cite, in business, time is money.
Decoding underperformance of entrepreneurship at the bottom of the pyramid: a literature review of the field
Authors: Chang Amber Y. , Xu Yalan
Published: February 2023

Purpose

Driving economic development at the bottom of the pyramid (BOP) is an enduring global challenge. While the market-based approach places hope on entrepreneurship as a major impetus to drive the underdeveloped economy, the performance of entrepreneurial businesses and their impact on poverty reduction are sometimes below expectations. This paper seeks to examine the factors that may be hindering entrepreneurship within the BOP context. This paper presents preliminary answers and provides research suggestions related to this question.

Design/methodology/approach

In order to identify the reasons behind the underperformance of entrepreneurship at the BOP, a comprehensive literature review was conducted to see what is already known about this puzzle.

Findings

By reviewing extant literature, four clusters of factors were found to shape entrepreneurial activities at BOP: (1) Individual-level factors may be restraining entrepreneurial activities within BOP context, (2) gender inequality at BOP is hindering female entrepreneurship, (3) insufficient institutional support is holding back entrepreneurial activities in BOP and (4) business development initiatives are making multi-faceted impacts on entrepreneurial activities in BOP.

Originality/value

This paper contributes to theory in that it is the first comprehensive review of literature on constraints of entrepreneurship in the context of BOP. In investigating influential factors of entrepreneurial success in the BOP context, the authors recognize four major influential forces that are shaping entrepreneurial processes at the bottom of the pyramid and further propose three directions of future research that are worthy for further exploration.