bluuebunny/crossref_metadata_2025 huggingface dataset:
Parkinsonian rest tremor can be distinguished from voluntary hand movements based on subthalamic and cortical activity using machine learning
Authors: Todorov Dmitrii , Schnitzler Alfons , Hirschmann Jan
Published: February 2023

Tremor is one of the cardinal symptoms of Parkinson’s disease. The neurophysiology of tremor is not completely understood, and so far it has not been possible to distinguish tremor from voluntary hand movements based on local brain signals.

Here, we re-analyzed magnetoencephalography and local field potential recordings from the subthalamic nucleus of six patients with Parkinson’s disease. Data were obtained after withdrawal from dopaminergic medication (Med Off) and after administration of levodopa (Med On). Using gradient-boosted tree learning, we classified epochs as tremor, self-paced fist-clenching, static forearm extension or tremor-free rest.

While decoding performance was low when using subthalamic activity as the only feature (balanced accuracy mean: 38%, std: 7%), we could distinguish the four different motor states when considering cortical and subthalamic features (balanced accuracy mean: 75%, std: 17%). Adding a single cortical area improved classification by 17% on average, as compared to classification based on subthalamic activity alone. In most patients, the most informative cortical areas were sensorimotor cortical regions. Decoding performance was similar in Med On and Med Off.

Our results demonstrate the advantage of monitoring cortical signals in addition to subthalamic activity for movement classification. By combining cortical recordings, subcortical recordings and machine learning, future adaptive systems might be able to detect tremor specifically and distinguish between several motor states.
A Novel Single Vector Intersectional AAV Strategy for Interrogating Cellular Diversity and Brain Function
Authors: Hughes Alex C. , Pollard Brittany G. , Xu Beisi , Gammons Jesse W. , Chapman Phillip , Bikoff Jay B. , Schwarz Lindsay A.
Published: February 2023

As the discovery of cellular diversity in the brain accelerates, so does the need for functional tools that target cells based on multiple features, such as gene expression and projection target. By selectively driving recombinase expression in a feature-specific manner, one can utilize intersectional strategies to conditionally promote payload expression only where multiple features overlap. We developed Conditional Viral Expression by Ribozyme Guided Degradation (ConVERGD), a single-construct intersectional targeting strategy that combines a self-cleaving ribozyme with traditional FLEx switches. ConVERGD offers benefits over existing platforms, such as expanded intersectionality, the ability to accommodate larger and more complex payloads, and a vector design that is easily modified to better facilitate rapid toolkit expansion. To demonstrate its utility for interrogating neural circuitry, we employed ConVERGD to target an unexplored subpopulation of norepinephrine (NE)-producing neurons within the rodent locus coeruleus (LC) identified via single-cell transcriptomic profiling to co-express the stress-related endogenous opioid gene prodynorphin (Pdyn). These studies showcase ConVERGD as a versatile tool for targeting diverse cell types and revealPdyn-expressing NE+LC neurons as a small neuronal subpopulation capable of driving anxiogenic behavioral responses in rodents.
Fast and artifact-free excitation multiplexing using synchronized image scanning
Authors: Bruggeman Ezra , Van den Eynde Robin , Amouroux Baptiste , Venneman Tom , Vanden Berghe Pieter , Müller Marcel , Vandenberg Wim , Dedecker Peter
Published: February 2023

We present the Resonator, a simple optical device that provides quasi-simultaneous fluorescence imaging with multiple excitation wavelengths. The device uses a resonant scanning mirror to periodically displace the sample image on a camera sensor at a rate that is much faster than the image acquisition rate. The excitation light is synchronized with the scanner motion to create two laterally shifted copies of the image, each containing the fluorescence excited by a single wavelength. The additional information is then encoded either into the point-spread function of the imaging or as multiple distinct images. Since this multiplexing is performed at very high rates, our design can eliminate or mitigate artifacts caused by temporal aliasing in conventional sequential imaging. We demonstrate the use of our system for the monitoring of fast light-induced dynamics in single quantum dots and for the imaging of Ca2+signalling in hippocampal neurons.
Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference
Authors: Cheemarla Nagarjuna R. , Mihaylova Valia T. , Watkins Timothy A. , Foxman Ellen F.
Published: February 2023

The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection using differentiated cultures of the human airway epithelium. Coexposure to IAV enhanced the tissue antiviral response during SARS-CoV-2 infection and suppressed SARS-CoV-2 replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the antiviral response and paradoxically restored SARS-CoV-2 replication. These results highlight the importance of diagnosing coinfections and compel further study of how coinfections impact the outcome of antiviral therapy.
Stimulus-induced theta band LFP oscillations format neuronal representations of social chemosignals in the mouse accessory olfactory bulb
Authors: Cohen Oksana , Kahan Anat , Steinberg Idan , Malinowski Sebastian , Rokni Dan , Spehr Marc , Ben-Shaul Yoram
Published: February 2023

Social communication is crucial for survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central VNS stage is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AOB-MCs). Recent studies provided important insights about the functional properties of AOB-MCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single unit activity in the AOB while presenting natural stimuli to adult male and female mice. Our recordings reveal prominent LFP theta band oscillatory episodes with a characteristic spatial pattern across the AOB. We find that the AOB network shows varying degrees of similarity to this pattern throughout an experiment, as a function of sensory stimulation. Analysis of LFP signal polarity and single unit activity indicate that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AOB-MCs and granule cells (GCs). Notably, spike times of many AOB-MCs are constrained to the negative LFP oscillation phase, in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.
Sharp wave ripple coupling in zebrafish hippocampus and basolateral amygdala
Authors: Blanco I. , Caccavano A. , Wu J. , Vicini S. , Glasgow E. , Conant K.
Published: February 2023

The mammalian hippocampus exhibits sharp wave events (1-30 Hz) with an often-present superimposed fast ripple oscillation (120-200 Hz) forming a sharp wave ripple (SWR) complex. During slow wave sleep or consummatory behaviors, SWRs result from the sequential spiking of hippocampal cell assemblies initially activated during imagined or learned experiences. SWRs occur in tandem with cortical/subcortical assemblies critical to the long-term storage of specific memory types. Leveraging juvenile zebrafish, we show that SWR events in their hippocampal homologue, the anterodorsolateral lobe (ADL), inex vivowhole-brains are locally generated and maintained. SWR events were also recorded in the basolateral amygdala (BLA). Concomitant single cell calcium imaging and local field potential (LFP) recordings showed that BLA SWs couple to ADL SWs. Calcium imaging recordings of whole-brains demonstrated that ADL and BLA SWRs are endogenously and spontaneously silenced by the activation of a more caudal population of putative cholinergic cells. Electrical stimulation of this caudal region silenced ADL SWs. Our results suggest that the SWR-generating circuit is evolutionarily conserved through shared acetylcholine modulating mechanisms. These findings further our understanding of neuronal population dynamics in the zebrafish brain and highlights their advantage for simultaneously recording SW/SWRs and single cell activity in diverse brain regions.
HiExM: high-throughput expansion microscopy enables scalable super-resolution imaging
Authors: Day John H. , Della Santina Catherine Marin , Maretich Pema , Auld Alexander L. , Schnieder Kirsten K. , Shin Tay , Boyden Edward S. , Boyer Laurie A.
Published: February 2023

Expansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate. Our method enables ∼4.2x expansion of cells within individual wells, across multiple wells, and between plates. We also demonstrate that HiExM can be combined with high-throughput confocal imaging platforms to greatly improve the ease and scalability of image acquisition. As an example, we analyzed the effects of doxorubicin, a known cardiotoxic agent, on human cardiomyocytes (CMs) as measured by Hoechst signal across the nucleus. We show a dose dependent effect on nuclear DNA that is not observed in unexpanded CMs, suggesting that HiExM improves the detection of cellular phenotypes in response to drug treatment. Our method broadens the application of ExM as a tool for scalable super-resolution imaging in biological research applications.

Significance Statement

Expansion microscopy (ExM) is an accessible and widely used technique for super-resolution imaging of fixed biological specimens. For many ExM users, slide-based sample preparation and manual imaging limit the number of experimental conditions and samples that can be processed in parallel. Here, we develop a simple and inexpensive device that enables ExM within the wells of a standard 96-well cell culture plate. We show that samples prepared with our workflow can be imaged with a high-throughput autonomous confocal microscope, allowing for scalable super-resolution image acquisition, greatly increasing data output. Our device retains the accessibility of ExM while extending its application to research questions that require the analysis of many conditions, treatments, and time points.
Temporal Dynamics of Genetically Heterogeneous Extended-Spectrum Cephalosporin ResistantEscherichia coliBloodstream Infections
Authors: Shropshire William C , Strope Benjamin , Anand Selvalakshmi Selvaraj , Bremer Jordan , McDaneld Patrick , Bhatti Micah M , Flores Anthony R , Kalia Awdhesh , Shelburne Samuel A
Published: February 2023

Extended-spectrum cephalosporin resistantEscherichia coli(ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ecinfections. To address the paucity of recent ESC-R-Ecmolecular epidemiology data in the United States, we used whole genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ecat a tertiary care cancer center in Houston, Texas collected from 2016-2020. During the study timeframe, there were 1154 indexE. colibloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ecdistinct from ESC-susceptibleE. coli(ESC-S-Ec), with cases peaking in the last six months of the calendar year. WGS of 297 ESC-R-Ecstrains revealed that while STc131 strains accounted for ∼45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ecclonal complexes.BlaCTX-Mvariants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification ofblaCTX-Mgenes was widely detected in ESC-R-Ecstrains, particularly in carbapenem non-susceptible, recurrent BSI strains.BlaCTX-M-55was significantly enriched within phylogroup A strains, and we identifiedblaCTX-M-55plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ecinfections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens.

IMPORTANCE

Given thatE. coliis the leading cause of worldwide ESC-REnterobacteralesinfections, we sought to assess the current molecular epidemiology of ESC-R-Ecusing a WGS analysis of many BSIs over a five-year period. We identified fluctuating temporal dynamics of ESC-R-Ecinfections, which has also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited, but genetically diverse group of ESC-R-Ecclonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R-Ecinfections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ecstrains. These data suggest that serious ESC-R-Ecinfections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.
Multiplicity ofAgrobacteriuminfection ofNicotiana benthamianafor transient DNA delivery
Authors: Carlson Erik D. , Rajniak Jakub , Sattely Elizabeth S.
Published: February 2023

Biological DNA transfer into plant cells mediated byAgrobacteriumrepresents one of the most powerful tools for the engineering and study of plant systems. Transient expression of transfer DNA (T-DNA) in particular enables rapid testing of gene products and has recently been harnessed for facile combinatorial expression of multiple genes. In analogous mammalian cell-based gene expression systems, a clear sense of the multiplicity of infection (MOI) allows users to predict and control viral transfection frequencies for applications requiring single vs. multiple transfection events per cell. Despite the value ofAgrobacterium-mediated transient transformation of plants, MOI has not been quantified. Establishing MOI forAgrobacteriumT-DNA delivery at the level of single plant cells would allow users to design genomic library delivery conditions (at most 1 event/cell), or maximize co-delivery of T-DNA loads from separateAgrobacterium(>1 event/cell). Here, we analyze the Poisson probability distribution of T-DNA transfer in leaf pavement cells to determine the MOI for the widely used model systemAgrobacteriumGV3101/Nicotiana benthamiana. These data delineate the relationship between an individualAgrobacteriumstrain infiltration OD600, plant cell perimeter and leaf age, as well as plant cell co-infection rates. Our analysis also establishes experimental regimes where the probability of near-simultaneous delivery of >20 unique T-DNAs to a given plant cell remains high throughout the leaf. We anticipate that these data will enable users to develop new approaches to in-leaf library development usingAgrobacteriumtransient expression and the reliable combinatorial assaying of multiple heterologous proteins in a single plant cell.
Junctophilin-2 Regulates Mitochondrial Metabolism
Authors: Prisco Sasha Z. , Hartweck Lynn M. , Kazmirczak Felipe , Mendelson Jenna B. , Deng Stephanie L. , Lahiri Satadru K. , Wehrens Xander H.T. , Prins Kurt W.
Published: February 2023

Right ventricular dysfunction (RVD) is a risk factor for mortality in multiple cardiovascular diseases, but approaches to combat RVD are lacking. Therapies used for left heart failure are largely ineffective in RVD, and thus the identification of molecules that augment RV function could improve outcomes in a wide-array of cardiac limitations. Junctophilin-2 (JPH2) is an essential protein that plays important roles in cardiomyocytes, including calcium handling/maintenance of t-tubule structure and gene transcription. Additionally, JPH2 may regulate mitochondrial function asJph2knockout mice exhibit cardiomyocyte mitochondrial swelling and cristae derangements. Moreover, JPH2 knockdown in embryonic stem cell-derived cardiomyocytes induces downregulation of the mitochondrial protein mitofusin-2 (MFN2), which disrupts mitochondrial cristae structure and transmembrane potential. Impaired mitochondrial metabolism drives RVD, and here we evaluated the mitochondrial role of JPH2. We showed JPH2 directly interacts with MFN2, ablation of JPH2 suppresses mitochondrial biogenesis, oxidative capacity, and impairs lipid handling in iPSC-CM. Gene therapy with AAV9-JPH2 corrects RV mitochondrial morphological defects, mitochondrial fatty acid metabolism enzyme regulation, and restores the RV lipidomic signature in the monocrotaline rat model of RVD. Finally, AAV-JPH2 improves RV function without altering PAH severity, showing JPH2 provides an inotropic effect to the dysfunction RV.
The clock-modulatory activity of Nobiletin suppresses adipogenesis via Wnt signaling
Authors: Xiong Xuekai , Kiperman Tali , Li Weini , Dhawan Sangeeta , Lee Jeongkyung , Yechoor Vijay , Ma Ke
Published: February 2023

The circadian clock machinery exerts transcriptional control to modulate adipogenesis and its disruption leads to the development of obesity. Here we report that Nobiletin, a clock amplitude-enhancing molecule, displays anti-adipogenic properties via activating a clock-controlled Wnt signaling pathway that suppresses adipocyte differentiation. Nobiletin augmented clock oscillation with period length shortening in the adipogenic mesenchymal precursor cells and preadipocytes, accompanied by an induction of Bmal1 and core clock components. Consistent with its circadian clock-modulatory activity, Nobiletin inhibited the lineage commitment and terminal differentiation of adipogenic progenitors. Mechanistically, we show that Nobiletin induced the re-activation of Wnt signaling during adipogenic differentiation via transcriptional up-regulation of key components of this pathway. Furthermore, Nobiletin administration in mice markedly reduced adipocyte hypertrophy, leading to a significant loss of fat mass and body weight reduction. Lastly, Nobiletin inhibited the maturation of primary preadipocytes and this effect was dependent on a functional clock regulation. Collectively, our findings uncover a novel activity of Nobiletin in suppressing adipocyte development, implicating its potential therapeutic application in countering obesity and its associated metabolic consequences.
Protein Crowding and Cholesterol Increase Cell Membrane Viscosity in a Temperature Dependent Manner
Authors: Fábián Balázs , Vattulainen Ilpo , Javanainen Matti
Published: February 2023

Shear viscosity of lipid membranes dictates how fast lipids, proteins, and other membrane constituents travel along the membrane and rotate around their principal axis, thus governing the rates of diffusion-limited reactions taking place at membranes. In this framework, the heterogeneity of biomembranes indicates that cells could regulate these ratesviavarying local viscosities. Unfortunately, experiments to probe membrane viscosity at various conditions are tedious and error prone. Molecular dynamics simulations provide a luring alternative, especially now that recent theoretical developments enable the elimination of finite-size effects in simulations. Here, we use different equilibrium methods to extract the shear viscosities of lipid membranes from both coarse-grained and all-atom molecular dynamics simulations. We systematically probe the variables relevant for cellular membranes, namely membrane protein crowding, cholesterol concentration, and the length and saturation level of the lipid acyl chains, as well as temperature. Our results highlight that in their physiologically relevant ranges, cholesterol concentration, protein concentration, and temperature have significantly larger effects on membrane viscosity than lipid acyl chain length and unsaturation level. Our work also provides the largest collection of membrane viscosity values from simulation to date, which can be used by the community to predict the diffusion coefficients or their trendsviathe Saffman–Delbrück description. Additionally, diffusion coefficients extracted from simulations exploiting periodic boundary conditions must be corrected for the finite-size effects prior to comparison with experiment, for which the present collection of viscosity values can readily be used. Finally, our thorough comparison to experiments suggests that there is some room for improvement in the description of bilayer dynamics provided by the present force fields.
MiR-4521 perturbs FOXM1-mediated DNA damage response in breast cancer
Authors: Kuthethur Raviprasad , Adiga Divya , Kandettu Amoolya , Jerome Maria Sona , Mallya Sandeep , Mumbrekar Kamalesh Dattaram , Kabekkodu Shama Prasada , Chakrabarty Sanjiban
Published: February 2023

Forkhead (FOX) transcription factors are involved in cell cycle control, cellular differentiation, maintenance of tissues, and aging. Mutation or aberrant expression of FOX proteins is associated with developmental disorders and cancers. FOXM1, an oncogenic transcription factor, is a promoter of cell proliferation and accelerated development of breast adenocarcinomas, squamous carcinoma of the head, neck, and cervix, and nasopharyngeal carcinoma. High FOXM1 expression is correlated with chemoresistance in patients treated with doxorubicin and Epirubicin by enhancing the DNA repair in breast cancer cells. Here, we showed that FOXM1 is a direct target of miR-4521 in breast cancer. Overexpression of miR-4521 significantly downregulated FOXM1 expression in breast cancer cells. FOXM1 regulates cell cycle progression and DNA damage response in breast cancer. We showed that miR-4521 expression leads to increased ROS levels and DNA damage in breast cancer cells. FOXM1 plays a critical role in ROS scavenging and promotes stemness which contributes to drug resistance in breast cancer. We observed that breast cancer cells stably expressing miR-4521 lead to cell cycle arrest, impaired FOXM1 mediated DNA damage response leading to increased cell death in breast cancer cells. Additionally, miR-4521-mediated FOXM1 downregulation perturbs cell proliferation, invasion, cell cycle progression, and epithelial-to-mesenchymal progression (EMT) in breast cancer. High FOXM1 expression has been associated with radio and chemoresistance contributing to poor patient survival in multiple cancers, including breast cancer. Our study showed that FOXM1 mediated DNA damage response could be targeted using miR-4521 mimics as a novel therapeutic for breast cancer.
CD38 promotes hematopoietic stem cell dormancy via c-Fos
Authors: Ibneeva Liliia , Singh Sumeet Pal , Sinha Anupam , Eski Sema Elif , Wehner Rebekka , Rupp Luise , Pérez-Valencia Juan Alberto , Gerbaulet Alexander , Reinhardt Susanne , Wobus Manja , von Bonin Malte , Sancho Jaime , Lund Frances , Dahl Andreas , Schmitz Marc , Bornhäuser Martin , Chavakis Triantafyllos , Wielockx Ben , Grinenko Tatyana
Published: February 2023

A subpopulation of deeply quiescent, so-called dormant hematopoietic stem cells (dHSCs) resides at the top of the hematopoietic hierarchy and serves as a reserve pool for HSCs possessing the greatest long-term blood repopulation capacity. The state of dormancy protects the HSC pool from exhaustion throughout life, however excessive dormancy may block an efficient response to hematological stresses. The mechanisms of HSC dormancy remain elusive, mainly due to the absence of surface markers that allow dHSC prompt isolation. Here, we identify CD38 as a novel surface marker for murine dHSCs that is broadly applicable. Moreover, we demonstrate that cyclic adenosine diphosphate ribose (cADPR), the product of CD38 cyclase activity, regulates the expression of the transcription factor c-Fos by increasing cytoplasmic Ca2+concentration. Strikingly, we uncover that c-Fos drives HSCs dormancy through the induction of the cell cycle inhibitor p57Kip2. Moreover, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells can promote human HSC quiescence. Together, CD38/cADPR/Ca2+/cFos/p57Kip2axis maintains HSC dormancy. Pharmacological manipulations of this pathway can provide new strategies to expand dHSCs for transplantation or to activate them during hematological stresses.
Catalytic antibodies in arrhythmogenic cardiomyopathy patients cleave desmoglein 2 and N-cadherin and impair cardiomyocyte cohesion
Authors: Yeruva Sunil , Stangner Konstanze , Jungwirth Anna , Hiermaier Matthias , Shoykhet Maria , Kugelmann Daniela , Hertl Michael , Egami Shohei , Ishii Norito , Koga Hiroshi , Hashimoto Takashi , Weis Michael , Beckmann Britt Maria , Biller Ruth , Schüttler Dominik , Kääb Stefan , Waschke Jens
Published: February 2023

Aims

Arrhythmogenic cardiomyopathy (AC) is a severe heart disease predisposing to ventricular arrhythmias and sudden cardiac death caused by mutations affecting intercalated disc (ICD) proteins and aggravated by physical exercise. Recently, autoantibodies targeting ICD proteins, including the desmosomal cadherin desmoglein 2 (DSG2), were reported in AC patients and were considered relevant for disease development and progression, particularly in patients without underlying pathogenic mutations. However, it is unclear at present whether these autoantibodies are pathogenic and by which mechanisms show specificity for DSG2 and thus can be used as a diagnostic tool.

Methods and Results

IgG fractions were purified from 15 AC patients and 4 healthy controls. Immunostainings dissociation assays, atomic force microscopy (AFM), western blot analysis and Triton-X-100 assays were performed utilizing human heart left ventricle tissue, HL-1 cells, and murine cardiac slices. Immunostainings revealed that autoantibodies against ICD proteins are prevalent in AC and most autoantibody fractions have catalytic properties and cleave the ICD adhesion molecules DSG2 and N-cadherin, thereby reducing cadherin interactions as revealed by AFM. Furthermore, most of the AC-IgG fractions causing loss of cardiomyocyte cohesion activated p38MAPK, which is known to contribute to a loss of desmosomal adhesion in different cell types, including cardiomyocytes. In addition, p38MAPK inhibition rescued the loss of cardiomyocyte cohesion induced by AC-IgGs.

Conclusion

Our study demonstrates that catalytic autoantibodies play a pathogenic role by cleaving ICD cadherins and thereby reducing cardiomyocyte cohesion by a mechanism involving p38MAPK activation. Finally, we conclude that DSG2 cleavage by autoantibodies could be used as a diagnostic tool for AC.
Structural and biophysical characterization of the Borna disease virus 1 phosphoprotein
Authors: Whitehead Jack D. , Grimes Jonathan M. , Keown Jeremy R.
Published: February 2023

Bornaviruses are RNA viruses with a mammalian, reptilian, and avian host range. The viruses infect neuronal cells and in rare cases cause a lethal encephalitis. The family Bornaviridae are part of the Mononegavirales order of viruses, which contain a nonsegmented viral genome. Mononegavirales encode a viral phosphoprotein (P) that binds both the viral polymerase (L) and the viral nucleoprotein (N). The P protein acts as a molecular chaperone and is required for the formation of a functional replication/transcription complex. In this study, the structure of the oligomerization domain of the phosphoprotein determined by X-ray crystallography is reported. The structural results are complemented with biophysical characterization using circular dichroism, differential scanning calorimetry and small-angle X-ray scattering. The data reveal the phosphoprotein to assemble into a stable tetramer, with the regions outside the oligomerization domain remaining highly flexible. A helix-breaking motif is observed between the α-helices at the midpoint of the oligomerization domain that appears to be conserved across the Bornaviridae. These data provide information on an important component of the bornavirus replication complex.
Evaluation of efficiency and ranking of Indian hotels and restaurants: a bootstrap DEA approach
Authors: Mahajan Varun , Mogha Sandeep Kumar , Pannala R.K.Pavan Kumar
Published: February 2023

Purpose

The main purpose of this paper is to determine the bias-corrected efficiencies and rankings of the selected hotels and restaurants (H&Rs) in India.

Design/methodology/approach

The data for the Indian H&R sector are collected from the Prowess database. The bootstrap data envelopment analysis (DEA) based on a constant return to scale (CRS), variable return to scale-input oriented (VRS-IP) and variable return to scale-output oriented (VRS-OP) are applied on H&Rs to obtain the bias-corrected efficiencies.

Findings

It is found that relative efficiencies using basic DEA methods of all the 45 H&Rs of India are overestimated. These efficiencies are corrected using bias correction through bootstrap DEA methods. The bounds for the efficiencies of each H&R are computed using all the adopted methods. All H&Rs are ranked using bias-corrected efficiencies, and the linear trend between ranks suggests that the H&Rs are ranked almost similarly by all the adopted methods.

Practical implications

To improve efficiency, Indian H&R companies must rethink their personnel needs by enhancing their workforce management capabilities. The government needs to extend more support to this sector by introducing a liberal legislation framework and supporting infrastructure policies.

Originality/value

There is a paucity of studies on H&Rs in India. The current study focused on measuring bias-corrected efficiencies of the selected H&Rs of India. This study is one of the few initiatives to explore bias-corrected efficiencies extensively using the bootstrap DEA method.
Does the transcultural problem really matter? An integrated approach to analyze barriers to eHealth SMEs’ development
Authors: Zhao Guoqing , Suklan Jana , Liu Shaofeng , Lopez Carmen , Hunter Lise
Published: February 2023

Purpose

In a competitive environment, eHealth small and medium-sized enterprises’ (SMEs’) barriers to survival differ from those of large enterprises. Empirical research on barriers to eHealth SMEs in less prosperous areas has been largely neglected. This study fills this gap by employing an integrated approach to analyze barriers to the development of eHealth SMEs. The purpose of this paper is to address this issue.

Design/methodology/approach

The authors collected data through semi-structured interviews and conducted thematic analysis to identify 16 barriers, which were used as inputs into total interpretive structural modeling (TISM) to build interrelationships among them and identify key barriers. Cross-impact matrix multiplication applied to classification (MICMAC) was then applied validate the TISM model and classify the 16 barriers into four categories.

Findings

This study makes significant contributions to theory by identifying new barriers and their interrelationships, distinguishing key barriers and classifying the barriers into four categories. The authors identify that transcultural problems are the key barrier and deserve particular attention. eHealth SMEs originating from regions with cultural value orientations, such as hierarchy and embeddedness, that differ from the UK’s affective autonomy orientation should strengthen their transcultural awareness when seeking to expand into UK markets.

Originality/value

By employing an integrated approach to analyze barriers that impede the development of eHealth SMEs in a less prosperous area of the UK, this study raises entrepreneurs’ awareness of running businesses in places with different cultural value orientations.
Wimp out or take off? Temporal dynamics in new venture effort after exposure to entrepreneurial obstacles
Authors: Li Ci-Rong , Yang Yanyu , Liu Jing , Lee Allan
Published: February 2023

Purpose

The present research integrates conservation of resources theory (COR) and adaptation theory to investigate the dynamics of entrepreneurs' reactions to obstacles. Furthermore, this research explores whether entrepreneurs' effort allocations following an obstacle influence how entrepreneurs appraise subsequent loss-related events. Finally, this research seeks to understand why some entrepreneurs handle obstacles better than others by considering the role of optimism.

Design/methodology/approach

This research utilized a longitudinal survey with 130 nascent entrepreneurs across 4 time periods. This research used a multivariate latent change analysis model to examine the temporal dynamics of new venture effort after exposure to obstacles.

Findings

The results indicated that entrepreneurial obstacles at time t were associated with decreased effort in new ventures at time t+1. Furthermore, new venture effort at time t was associated with decreased effort in new ventures at time t+1. The results also demonstrated that the allocation of greater effort may lead to a decrease in subsequent obstacle appraisals, a relationship that also varies as a function of nascent entrepreneurs' optimism.

Originality/value

This research extends the understanding of the dynamic pattern of reactions following exposure to entrepreneurial obstacles. The findings suggest that, rather than being straightforward, reactions are likely to ebb and flow over time.
The incentive effect of government subsidies on the digital transformation of manufacturing enterprises
Authors: Zhao Xueqi , Zhao Longwen , Sun Xiaozhe , Xing Yibing
Published: February 2023

Purpose

China's digital economy is flourishing and playing a pivotal role in the national economy. Government subsidies, as an important tool for the national treasury, are a “reassurance” for the digital transformation of manufacturing enterprises. The purpose of this paper is to investigate the relations between the digital transformation of manufacturing enterprises and government subsidies to provide inspiration for promoting the digitization and upgrading of China's manufacturing industry and facilitate enterprises' innovative development.

Design/methodology/approach

Based on the panel data of 2,928 manufacturing listed companies in China from 2016 to 2020, this paper empirically tests the effect of subsidies on the digital transformation of manufacturing enterprises using fixed-effect econometric regression.

Findings

The results illustrate that subsidies effectively incentivize digital transformation in manufacturing enterprises, and verify different situations through heterogeneity. Further analysis of the moderating effect shows that the innovation level and servitization level of manufacturing enterprises positively moderated the relationship between government subsidies and the enterprise's digital transformation.

Originality/value

Based on Chinese manufacturing enterprise samples, this paper empirically tests the incentive effect of government subsidies on the digital transformation of manufacturing enterprises, therefore clarifying the main regulatory effects. This paper could provide enlightenment for manufacturing enterprises to make good use of government subsidies to improve their digital ability, thereby enhancing competitiveness in the digital economy era.
Consecutive surgeries with complications: the impact of scheduling decisions
Authors: Diamant Adam , Shevchenko Anton , Johnston David , Quereshy Fayez
Published: February 2023

Purpose

The authors determine how the scheduling and sequencing of surgeries by surgeons impacts the rate of post-surgical complications and patient length-of-stay in the hospital.

Design/methodology/approach

Leveraging a dataset of 29,169 surgeries performed by 111 surgeons from a large hospital network in Ontario, Canada, the authors perform a matched case-control regression analysis. The empirical findings are contextualized by interviews with surgeons from the authors’ dataset.

Findings

Surgical complications and longer hospital stays are more likely to occur in technically complex surgeries that follow a similarly complex surgery. The increased complication risk and length-of-hospital-stay is not mitigated by scheduling greater slack time between surgeries nor is it isolated to a few problematic surgery types, surgeons, surgical team configurations or temporal factors such as the timing of surgery within an operating day.

Research limitations/implications

There are four major limitations: (1) the inability to access data that reveals the cognition behind the behavior of the task performer and then directly links this behavior to quality outcomes; (2) the authors’ definition of task complexity may be too simplistic; (3) the authors’ analysis is predicated on the fact that surgeons in the study are independent contractors with hospital privileges and are responsible for scheduling the patients they operate on rather than outsourcing this responsibility to a scheduler (i.e. either a software system or an administrative professional); (4) although the empirical strategy attempts to control for confounding factors and selection bias in the estimate of the treatment effects, the authors cannot rule out that an unobserved confounder may be driving the results.

Practical implications

The study demonstrates that the scheduling and sequencing of patients can affect service quality outcomes (i.e. post-surgical complications) and investigates the effect that two operational levers have on performance. In particular, the authors find that introducing additional slack time between surgeries does not reduce the odds of back-to-back complications. This result runs counter to the traditional operations management perspective, which suggests scheduling more slack time between tasks may prevent or mitigate issues as they arise. However, the authors do find evidence suggesting that the risk of back-to-back complications may be reduced when surgical pairings are less complex and when the method involved in performing consecutive surgeries varies. Thus, interspersing procedures of different complexity levels may help to prevent poor quality outcomes.

Originality/value

The authors empirically connect choices made in scheduling work that varies in task complexity and to patient-centric health outcomes. The results have implications for achieving high-quality outcomes in settings where professionals deliver a variety of technically complex services.
Dynamic coal blending under sustainability concerns: a case study from the Indian steel industry
Authors: Ahmad Md Tanweer , Firouz Mohammad , Srivastava Nishit Kumar
Published: February 2023

Purpose

Increasing scarcity of natural resources and the adverse effects of unsustainable practices call for more and more efficient management strategies in the energy industry. The quality of the coke plays a significant role in the quality and durability of the output steel which is produced using the energy from the coal. This paper aims to investigate the dynamic coal blending problem under overall cost and coke quality constraints in the steel industry within a periodic cycle of operations.

Design/methodology/approach

Considering the variability of the natural properties over a periodic cycle, this study proposes a multi-period mixed-integer non-linear programming formulation to optimize the total blending costs while taking various coke quality constraints into account. Besides, this study applies factorial design to investigate about the significant effect of coal proportions as well as improvement into the overall cost of blending.

Findings

In this case study, utilizing real data from a coal blending facility in India, through a factorial design, the authors obtain optimal desirable levels of coal proportions and their criticality levels towards the total cost of blending (TCB) or objective function. This analysis reflects the role of the coke quality constraints in the objective function value while characterizing the price of sustainability for the case study among other critical insights.

Originality/value

Objective function (or TCB) includes basic coal cost, movement cost and environmental costs during the coal and coke processing at a coke-oven and blast furnace of steel industry. The price of sustainability provides managerial insights on that sacrifices the industry has to make in order to become more “sustainable”.
Foreign divestment, economic growth and development in South Africa: an empirical analysis
Authors: Matekenya Weliswa , Moyo Clement
Published: February 2023

Purpose

The purpose of this study is to investigate the effect of foreign direct divestments (FDD) on economic growth and development in South Africa for the period 1991–2019.

Design/methodology/approach

The non-linear autoregressive distributed lag technique is used for the empirical analysis. Two regression models are specified, one for economic growth and the other for development which is proxied by poverty.

Findings

The empirical results suggest that foreign divestments are detrimental to both economic growth and development. Furthermore, the results suggest that the negative effects of foreign divestments outweigh the positive effects of FDI inflows.

Practical implications

South African policymakers should thus use policies that promote the retention of FDI inflows together with those that attract inflows. Furthermore, policies that promote economic freedom such as transparency and reduction in the time frame for granting government permits for business operations are also of paramount importance.

Originality/value

Most of the available literature on FDD focuses on the firm perspective. Available studies on the effect of FDD on economic growth do not investigate the effect of divestment on economic development. Economic growth is a necessary but not a sufficient condition for the achievement of socioeconomic development.
Blockchain technology for sustainable development: a systematic literature review
Authors: Joshi Parikshit , Tewari Vijaishri , Kumar Shailendra , Singh Anshu
Published: February 2023

Purpose

Blockchain technology (BCT) is one of the latest disruptive innovations, brought along with-it immense scope of diverse applications contributing towards sustainable development (SD). The consistent increase in the publications reveal that the application of BCT for SD has become popular among researchers and practitioners in past few years, in turn, urged for a systematic literature review (SLR) to get an insight into the research journey travelled so far and setting directions for future research in this area. Therefore, this study aims to identify, map and synthesize the available literature on application of BCT for SD.

Design/methodology/approach

The automatic and manual search resulted into 1,277 studies from Scopus and Web of Science database. Further applying inclusion and exclusion criterion resulted in bringing out total of 157 studies, which were termed as primary studies. Based on the results of descriptive analysis, conducted through Bibliometric and VOSviewer software, the characteristics of BCT and its key capabilities, contributing towards shaping the recent SD literature, were critically examined. Identified research themes for clustering primary studies were aligned with United Nations Sustainability Development Goals (UNSDG). A mind-map was also prepared on the basis of thematic classification of primary studies.

Findings

The research themes “business practice and economic sustainability”, “agriculture and food security” and “business practice and environment sustainability” were found to be the focal points of scholarly attention. Synthesis and analysis of primary studies resulted into classification of research gaps under four categories – theoretical foundation, methodological limitation, research themes and technology implementation challenges. The study was concluded by sensitizing and sanitizing the concrete research questions for future research.

Research limitations/implications

The research findings shall be a roadmap for research scholars, academicians and practitioners to comprehend the present state of knowledge in the domain of “BCT application for SD” and decide upon adopting the future course of action to attain the UNSDGs by the year 2030.

Originality/value

To the best of the authors’ knowledge, the current study is the first attempt in its own sense to analyse and synthesize the available literature on “attaining SD through BCT” using SLR approach.
Idiosyncrasies, isomorphic pressures and decoupling in technology platform business
Authors: Iman Nofie
Published: February 2023

Purpose

This study aims to explore the ways and contexts in which fintech firms are being developed, operated in the market and responds to competitive pressures and technological changes through isomorphism and decoupling mechanism.

Design/methodology/approach

How can new technology platform business successfully distinguish themselves from competitors while also ensuring that they are seen as legitimate and appropriate? This paper draws on a case study of fintech start-ups in Indonesia.

Findings

This study shows that managing market pressures for distinctiveness (customer-appealing) versus business pressures for profits (investor returns) drives firms’ quest for optimal distinctiveness. It is evident that fintech firms increase their control by consolidating themselves through their industrial association and by forming a close relationship with regulators. However, to escape the iron cage of the field, they increasingly control the coupling of profitability and compliance.

Originality/value

Through a qualitative-inductive approach, this study provides insights into technological development of platform business in the context of financial services and responsive movement towards cashless society.