bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 antigen testing as a case study
Authors: Hart William S , Park Hyeongki , Jeong Yong Dam , Kim Kwang Su , Yoshimura Raiki , Thompson Robin N , Iwami Shingo
Published: March 2023

In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multi-scale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multi-scale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.
Heart failure, female sex and atrial fibrillation are the main drivers of human atrial cardiomyopathy: results from the CATCH ME consortium
Authors: Winters J. , Isaacs A. , Zeemering S. , Kawczynski M. , Maesen B. , Maessen J. , Bidar E. , Boukens B. , Hermans B. , van Hunnik A , Casadei B. , Fabritz L. , Chua W. , Sommerfeld L.C. , Guasch E. , Mont L. , Batlle M. , Hatem S. , Kirchhof P. , Wakili R. , Sinner M.F. , Kääb S. , Stoll M. , Goette A. , Verheule S. , Schotten U.
Published: March 2023

Background

Atrial cardiomyopathy (AtCM) is emerging as an independent prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are histological hallmarks of atCM. However, the contribution of various etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been robustly quantified. We aimed to evaluate the association between histological features of atCM and the clinical phenotype.

Methods

We examined left (LA, n=95) and right (RA, n=76) atrial appendages sampled from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed using the JavaCyte algorithm, following staining with agglutinin (WGA), CD31 and vimentin. The contributions of AF, heart failure (HF), sex and age to histological characteristics were determined in a multivariate model. K-means clustering of 6 histological features was performed to identify different types of atCM.

Results

In both LA and RA, persistent AF was associated with increased endomysial fibrosis (LA:+1.07±0.41µm,p=0.01; RA:+0.89±0.43µm,p=0.032), whereas total extracellular matrix (ECM) content was unchanged in AF. Men had larger cardiomyocytes (LA:+1.87±0.72μm,p=0.012), while women had a higher degree of endomysial fibrosis (LA:+0.99±0.51µm,p=0.048). Heart failure patients showed more endomysial fibrosis (LA:+1.79±0.41µm,p<0.001) and ECM content (LA:+2.93±1.15%, p=0.014), and a higher capillary density (LA:+0.14±0.06,p=0.032) and size (LA:+0.48±0.23µm,p=0.041; RA:+0.31±0.16µm,p=0.047). Clustering of samples based on structural features identified 2 distinct atCM phenotypes; one characterized by enhanced endomysial fibrosis (LA:+3.35µm,p<0.001; RA:+1.88μm,p<0.001), ECM content (LA:+5.68%,p<0.001; RA:+7.78%,p<0.001), and a higher fibroblast density (LA:+4.79%,p<0,001) and one characterized by cardiomyocyte hypertrophy (LA:+1.20µm,p=0.009; RA:+2.95µm, p<0.001). Patients with fibrotic atCM were more often female (LA:OR=1.31,p=0.003; RA:OR=1.55,p=0.003), had more often persistent AF (LA:OR=1.23,p=0.031) or heart failure (LA:OR=1.62,p<0.001) whereas hypertrophic features were more common in men (LA:OR=1.31,p=0.031; RA:OR= 1.55,p=0.003).

Conclusions

AtCM phenotypes vary with patient characteristics. Fibrotic atCM is associated with female sex, persistent AF and heart failure, while hypertrophic features are more common in men.
Long-term Exposure to Ambient PM2.5and Hospitalizations for Myocardial Infarction among U.S. Residents: A Difference-in-Differences Analysis
Authors: Wang Yichen , Qiu Xinye , Wei Yaguang , Schwartz Joel D.
Published: March 2023

Background

Air pollution has been recognized as an untraditional risk factor for myocardial infarction (MI). However, the MI risk attributable to long-term exposure to fine particulate matter (PM2.5) is unclear, especially in younger populations, and few studies represented the general population.

Methods

We applied the difference-in-differences approach to estimate the relationship between annual PM2.5exposure and hospitalizations for MI among U.S. residents and further identified potential susceptible subpopulations. All hospital admissions for MI in ten U.S. states over the period 2002-2016 were obtained from the Healthcare Cost and Utilization Project State Inpatient Database.

Results

In total, 1,914,684 MI hospital admissions from 8,106 ZIP codes in ten states from 2002 to 2016 were included in this study. We observed a 1.35% (95% CI: 1.11-1.59%) increase in MI hospitalization rate for 1 μg/m3increase in annual PM2.5exposure. The estimate was robust to adjustment for surface pressure, relative humidity and co-pollutants. In the population with exposure at or below 12 μg/m3, there was a larger increment of 2.17% (95% CI: 1.79-2.56%) in hospitalization rate associated with 1 μg/m3increase in PM2.5. Young people (0-34 years) and elderly people (≥75 years) were the two most susceptible age groups. Residents living in more densely populated or poorer areas and individuals with comorbidities were observed to be at a greater risk.

Conclusions

This study indicates long-term residential exposure to PM2.5could lead to increased risk of MI among U.S. general population. The association persists below current standards.

Clinical Perspective

What is new?

Long-term exposure to PM2.5increased the risk of myocardial infarction in the general U.S. population.

Young individuals aged 0-34 years had the highest relative risk from long-term exposure to PM2.5, and elderly people aged ≥75 years were the second most susceptible to the effects.

Individuals with iron deficiency anemia, psychosis, and renal failure were more susceptible to the long-term effects of PM2.5on MI.

What are the clinical implications?

Long-term PM2.5exposure is one of the important modifiable environmental risk factors for myocardial infarction, therefore, air pollution control and behavioral interventions should be taken to prevent the occurrence of myocardial infarction.
Solid Tumor Treatment via Augmentation of Bioactive C6 Ceramide Levels with Thermally Ablative Focused Ultrasound
Authors: Thim E. Andrew , Fox Todd , Deering Tye , Vass Luke R. , Sheybani Natasha D. , Kester Mark , Price Richard J.
Published: March 2023

Sparse scan partial thermal ablation (TA) with focused ultrasound (FUS) may be deployed to treat solid tumors and increase delivery of systemically administered therapeutics. Further, C6-ceramide-loaded nanoliposomes (CNLs), which rely upon the enhanced permeation and retention (EPR) effect for delivery, have shown promise for treating solid tumors and are being tested in clinical trials. Here, our objective was to determine whether CNLs synergize with TA in the control of 4T1 breast tumors. CNL-monotherapy of 4T1 tumors yielded significant intratumoral bioactive C6 accumulation by the EPR effect, but tumor growth was not controlled. TA increased bioactive C6 accumulation by ∼12.5-fold over the EPR effect. In addition, TA+CNL caused shifts in long-chain to very-long-chain ceramide ratios (i.e., C16/24 and C18/C24) that could potentially contribute to tumor control. Nonetheless, these changes in intratumoral ceramide levels were still insufficient to confer tumor growth control beyond that achieved when combining with TA with control “ghost” nanoliposomes (GNL). While this lack of synergy could be due to increased “pro-tumor” sphingosine-1-phosphate (S1P) levels, this is unlikely because S1P levels exhibited only a moderate and statistically insignificant increase with TA+CNL. In vitro studies showed that 4T1 cells are highly resistant to C6, offering the most likely explanation for the inability of TA to synergize with CNL. Thus, while our results show that sparse scan TA is a powerful approach for markedly enhancing CNL delivery and generating “anti-tumor” shifts in long-chain to very-long-chain ceramide ratios, resistance of the tumor to C6 can still be a rate-limiting factor for some solid tumor types.
Presynaptic and Postsynaptic Determinants of the Functional Connectivity Between the Claustrum and Anterior Cingulate Cortex
Authors: de la Torre-Martínez Roberto , Chia Zach , Tokarska Anna , Frost-Nylén Johanna , Augustine George J , Silberberg Gilad
Published: March 2023

The claustrum (CLA) is a brain nucleus located between the insula and lateral striatum, implicated in a wide range of behaviors. Underpinning the different behavioral phenotypes is the connectivity between the claustrum and various cortical regions, including the anterior cingulate cortex (ACC). CLA projection neurons are glutamatergic neurons, however, the impact of CLA on its cortical targets has been shown in some studies to be inhibitory. Such inhibition is likely to arise from claustral activation of cortical interneurons, however, the intricate synaptic connectivity between different CLA and cortical cell types is not known. Here, we combinein vivoandex vivoelectrophysiology and optogenetics to reveal the functional organization of the CLA-ACC pathway according to the identity of its pre- and postsynaptic populations. Optogenetic stimulation of CLA neurons in awake mice resulted in multiphasic excitatory and inhibitory responses in ACC cells, which depended on the layer, cell type, and stimulated CLA population. Usingex vivopaired recordings in ACC, monosynaptic responses were recorded in pyramidal cells and different types of interneurons following photostimulation of CLA-ACC synaptic terminals. CLA axons formed monosynaptic connections in all ACC cortical layers, but the probability and strength of synaptic responses depended on the type of CLA projection, target layer in ACC, and the type of postsynaptic neuron. This intricate organization of the CLA-ACC pathway may explain the complex impact of CLA on ACC and other cortical regions, thus resolving some of the discrepancies in the field and shedding light on the functional role CLA plays in cortical function.
Ex vivoprimary liver sections recapitulate disease phenotype and therapeutic rescue for liver monogenic diseases
Authors: Perocheau Dany , Gurung Sonam , Touramanidou Loukia , Duff Claire , Sharma Garima , Sebire Neil , Finn Patrick F. , Cavedon Alex , Siddiqui Summar , Rice Lisa , Martini Paolo G.V. , Frassetto Andrea , Baruteau Julien
Published: March 2023

In academic research and the pharmaceutical industry,in vitrosingle cell line cultures andin vivoanimal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have limitations, with incomplete reproduction of pathophysiological characteristics and absence of 3-dimensional architecture with cell lines or the use of live animals brings ethical considerations, limiting the experimental scale and design. The use of precision-cut tissue slices can bridge the gap between these mainstream models as this technique combines the advantages of studying all cell sub-types whilst preserving the tissue-matrix architecture, thereby closely mimicking a mini-organ. Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers. We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.
Visualization of translation reorganization upon persistent collision stress in mammalian cells
Authors: Fedry Juliette , Silva Joana , Vanevic Mihajlo , Fronik Stanley , Mechulam Yves , Schmitt Emmanuelle , Georges Amédée des , Faller William , Förster Friedrich
Published: March 2023

Aberrantly slow mRNA translation leads to ribosome stalling and subsequent collision with the trailing neighbor. Ribosome collisions have recently been shown to act as stress sensors in the cell, with the ability to trigger stress responses balancing survival and apoptotic cell-fate decisions depending on the stress level. However, we lack a molecular understanding of the reorganization of translation processes over time in mammalian cells exposed to an unresolved collision stress. Here we visualize the effect of a persistent collision stress on translation usingin situcryo electron tomography. We observe that low dose anisomycin collision stress leads to the stabilization of Z-site bound tRNA on elongating 80S ribosomes, as well as to the accumulation of an off-pathway 80S complex possibly resulting from collision splitting events. We visualize collided disomesin situ, occurring on compressed polysomes and revealing a stabilized geometry involving the Z-tRNA and L1 stalk on the stalled ribosome, and eEF2 bound to its collided rotated-2 neighbor. In addition, non-functional post-splitting 60S complexes accumulate in the stressed cells, indicating a limiting Ribosome associated Quality Control clearing rate. Finally, we observe the apparition of tRNA-bound aberrant 40S complexes shifting with the stress timepoint, suggesting a succession of different initiation inhibition mechanisms over time. Altogether, our work visualizes the changes of translation complexes under persistent collision stress in mammalian cells, indicating how perturbations in initiation, elongation and quality control processes contribute to an overall reduced protein synthesis.

Usingin situcryo electron tomography we visualized the reorganization of mammalian translation processes during a persistent collision stress.
Chiropterans are a hotspot for horizontal transfer of DNA transposons in Mammalia
Authors: Paulat Nicole S , Storer Jessica M , Moreno-Santillán Diana D , Osmanski Austin B , Sullivan Kevin AM , Grimshaw Jenna R , Korstian Jennifer , Halsey Michaela , Garcia Carlos J , Crookshanks Claudia , Roberts Jaquelyn , Smit Arian FA , Hubley Robert , Rosen Jeb , Teeling Emma C , Vernes Sonja C , Myers Eugene , Pippel Martin , Brown Thomas , Hiller Michael ,   Zoonomia Consortium, Rojas Danny , Dávalos Liliana M , Lindblad-Toh Kerstin , Karlsson Elinor K , Ray David A
Published: March 2023

Horizontal transfer of transposable elements is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of transposable elements at what appears to be a high rate compared to other mammals. We investigated the occurrence of horizontally transferred DNA transposons involving bats. We found over 200 putative horizontally transferred elements within bats; sixteen transposons were shared across distantly related mammalian clades and two other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats.
Surfactant protein A promotes atherosclerosis through mediating macrophage foam cell formation
Authors: King Skylar D. , Cai Dunpeng , Fraunfelder Mikayla M. , Chen Shi-You
Published: March 2023

BACKGROUND

Atherosclerosis is a progressive inflammatory disease where macrophage foam cells play a central role in the pathogenesis. Surfactant protein A (SPA) is a lipid-associating protein involved with regulating macrophage function in various inflammatory diseases. However, the role of SPA in atherosclerosis and macrophage foam cell formation has not been investigated.

METHODS

Primary resident peritoneal macrophages were extracted from wildtype (WT) and SPA deficient (SPA-/-) mice to determine the functional effects of SPA in macrophage foam cell formation. SPA expression was assessed in healthy vessels and atherosclerotic aortic tissue from the human coronary artery and WT or apolipoprotein e-deficient (ApoE-/-) mice brachiocephalic arteries fed high fat diets (HFD) for 4 weeks. Hypercholesteremic WT and SPA-/-mice fed a HFD for 6 weeks were investigated for atherosclerotic lesionsin vivo.

RESULTS

In vitroexperiments revealed that global SPA deficiency reduced intracellular cholesterol accumulation and macrophage foam cell formation. Mechanistically, SPA-/-dramatically decreased CD36 cellular and mRNA expression. SPA expression was increased in atherosclerotic lesions in humans and ApoE-/-mice.In vivoSPA deficiency attenuated atherosclerosis and reduced the number of lesion-associated macrophage foam cells.

CONCLUSIONS

Our results elucidate that SPA is a novel factor for atherosclerosis development. SPA enhances macrophage foam cell formation and atherosclerosis through increasing scavenger receptor cluster of differentiation antigen 36 (CD36) expression.
Meningeal origins and dynamics of perivascular fibroblast development on the mouse cerebral vasculature
Authors: Jones Hannah E. , Coelho-Santos Vanessa , Bonney Stephanie K. , Abrams Kelsey A. , Shih Andy Y. , Siegenthaler Julie A.
Published: March 2023

Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs drive fibrosis following injury but their homeostatic functions are not well detailed. In mice, PVFs were previously shown to be absent from most brain regions at birth and are only detected postnatally within the cerebral cortex. However, the origin, timing, and cellular mechanisms of PVF development are not known. We usedCol1a1-GFPandCol1a2-CreERTtransgenic mice to track PVF developmental timing and progression in postnatal mice. Using a combination of lineage tracing andin vivoimaging we show that brain PVFs originate from the meninges and are first seen on parenchymal cerebrovasculature at postnatal day (P)5. After P5, PVF coverage of the cerebrovasculature rapidly expands via mechanisms of local cell proliferation and migration from the meninges, reaching adult levels at P14. Finally, we show that PVFs and perivascular macrophages (PVMs) develop concurrently along postnatal cerebral blood vessels, where the location and depth of PVMs and PVFs highly correlate. These findings provide the first complete timeline for PVF development in the brain, enabling future work into how PVF development is coordinated with cell types and structures in and around the perivascular spaces to support normal CNS vascular function.

Brain perivascular fibroblasts migrate from their origin in the meninges and proliferate locally to fully cover penetrating vessels during postnatal mouse development.
Coordination of Alternative Splicing and Alternative Polyadenylation revealed by Targeted Long-Read Sequencing
Authors: Zhang Zhiping , Bae Bongmin , Cuddleston Winston H. , Miura Pedro
Published: March 2023

Nervous system development is associated with extensive regulation of alternative splicing (AS) and alternative polyadenylation (APA). AS and APA have been extensively studied in isolation, but little is known about how these processes are coordinated. Here, the coordination of cassette exon (CE) splicing and APA inDrosophilawas investigated using a targeted long-read sequencing approach we call Pull-a-Long-Seq (PL-Seq). This cost-effective method uses cDNA pulldown and Nanopore sequencing combined with an analysis pipeline to resolve the connectivity of alternative exons to alternative 3’ ends. Using PL-Seq, we identified genes that exhibit significant differences in CE splicing depending on connectivity to short versus long 3’UTRs. Genomic long 3’UTR deletion was found to alter upstream CE splicing in short 3’UTR isoforms and ELAV loss differentially affected CE splicing depending on connectivity to alternative 3’UTRs. This work highlights the importance of considering connectivity to alternative 3’UTRs when monitoring AS events.
Inoviridaeprophage and bacterial host dynamics during diversification, succession and Atlantic invasion of Pacific-nativeVibrio parahaemolyticus
Authors: Foxall Randi L. , Means Jillian , Marcinkiewicz Ashley L. , Schillaci Christopher , DeRosia-Banick Kristin , Xu Feng , Hall Jeffrey A. , Jones Stephen H. , Cooper Vaughn S. , Whistler Cheryl A.
Published: March 2023

The epidemiology ofVibrio parahaemolyticus,the leading cause of seafood-borne bacterial gastroenteritis of humans world-wide, dramatically changed in the United States following the establishment of a Pacific native lineage called sequence type (ST) 36 in the Atlantic. In this study we used phylogeography based on traceback to environmental source locations and comparative genomics to identify features that promoted evolution, dispersal, and competitive dominance of ST36. The major genomic differentiation and competitive success of ST36 was associated with a striking succession of filamentous prophage in the familyInoviridae(inoviruses), including loss of an inovirus prophage that had been maintained for decades in the endemic north Pacific population. Subsequently, at least five distinct progenitors arising from this diversification translocated from the Pacific into the Atlantic and established four geographically defined clonal subpopulations with remarkably low migration or mixing. Founders of two prevailing Atlantic subpopulations each acquired new stable and diagnostic inoviruses while other subpopulations that apparently declined did not. Broader surveys indicate inoviruses are common and active among the global population ofV. parahaemolyticusand though inovirus replacements, such as in ST36, appear to be infrequent, they are notable in pathogenic lineages that dispersed.

Importance

An understanding of the processes that contribute to emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis ofVibrio parahaemolyticushosts combined with analysis of theirInoviridaephage resolved ambiguities of diversification dynamics which preceded successful Atlantic invasion by the epidemiologically predominant ST36 lineage. It has been established experimentally that filamentous phage can limit host recombination, but here we show that phage loss is linked to rapid bacterial host diversification during epidemic spread in natural ecosystems alluding to a potential role for ubiquitous inoviruses in the adaptability of pathogens. This work paves the way for functional analyses to define the contribution of inoviruses in the evolutionary dynamics of environmentally transmitted pathogens.
Kinetochore dynein is sufficient to biorient chromosomes and remodel the outer kinetochore
Authors: Prevo Bram , Cheerambathur Dhanya K. , Earnshaw William C. , Desai Arshad
Published: March 2023

Multiple microtubule-directed activities concentrate on chromosomes during mitosis to ensure their accurate distribution to daughter cells. These activities include couplers and dynamics regulators localized at the kinetochore, the specialized microtubule interface built on centromeric chromatin, as well as motor proteins recruited to kinetochores and to mitotic chromatin. Here, we describe anin vivoreconstruction approach in which the effect of removing the major microtubule-directed activities on mitotic chromosomes is compared to the selective presence of individual activities. This approach revealed that the kinetochore dynein module, comprised of the minus end-directed motor cytoplasmic dynein and its kinetochore-specific adapters, is sufficient to biorient chromosomes and to remodel outer kinetochore composition following microtubule attachment; by contrast, the kinetochore dynein module is unable to support chromosome congression. The chromosome-autonomous action of kinetochore dynein, in the absence of the other major microtubule-directed factors on chromosomes, rotates and orients a substantial proportion of chromosomes such that their sister chromatids attach to opposite spindle poles. In tight coupling with orientation, the kinetochore dynein module drives removal of outermost kinetochore components, including the dynein motor itself and spindle checkpoint activators. The removal is independent of the other major microtubule-directed activities and kinetochore-localized protein phosphatase 1, suggesting that it is intrinsic to the kinetochore dynein module. These observations indicate that the kinetochore dynein module has the ability coordinate chromosome biorientation with attachment state-sensitive remodeling of the outer kinetochore that facilitates cell cycle progression.
Proximity mapping of desmosomes reveals a striking shift in their molecular neighbourhood associated with maturation
Authors: Fülle Judith B. , de Almeida Rogerio Alves , Lawless Craig , Yanes Bian , Lane E. Birgitte , Garrod David R. , Ballestrem Christoph
Published: March 2023

Desmosomes are multiprotein adhesion complexes that link intermediate filaments to the plasma membrane, ensuring the mechanical integrity of cells across tissues, but how they participate in the wider signalling network to exert their full function is unclear. To investigate this we carried out multiplexed protein proximity mapping using biotinylation (BioID). The combined interactomes of the essential desmosomal proteins desmocollin 2a, plakoglobin and plakophilin 2a (Pkp2a) in Madin-Darby canine kidney epithelial cells were mapped and their differences and commonalities characterised as desmosome matured from Ca2+-dependence to the mature, Ca2+-independent, hyperadhesive state, which predominates in tissues. Results suggest that individual desmosomal proteins have distinct roles in connecting to cellular signalling pathways and that these roles alter substantially when cells change their adhesion state. The data provide further support for a dualistic concept of desmosomes in which the properties of Pkp2a differ from those of the other, more stable proteins. This body of data provides an invaluable resource for analysis of desmosome function.
Synthetic cell-cycle regulation identifies Mif2CENP-Cas a CDK phospho-target at the kinetochore
Authors: Klemm Cinzia , Ólafsson Guðjón , Thorpe Peter H.
Published: March 2023

Protein phosphorylation regulates multiple cellular processes including cell-cycle progression, which is driven by highly conserved cyclin-dependent kinases (CDKs). CDKs are controlled by the oscillating levels of activating cyclins and the activity peaks during mitosis to promote chromosome segregation. However, with some exceptions, we do not understand how the multitude of CDK-phosphorylated residues within the proteome drive cell-cycle progression nor which CDK phosphorylation events are necessary. To identify yeast proteins whose phospho-regulation is most critical for cell-cycle progression, we created a synthetic CDK complex and systematically recruited this to proteins involved in chromosome segregation using the Synthetic Physical Interactions (SPI) method. We found that targeted recruitment of synthetic CDK to the centromeric protein Mif2CENP-Cleads to enrichment of Mif2CENP-Cat centromeres and arrested cells in late mitosis. We then identified putative CDK consensus sites on Mif2CENP-Cwhich aid Mif2CENP-Clocalisation at centromeres and showed that CDK- dependent Mif2CENP-Cphosphorylation is important for its stable kinetochore localisation.

To identify cellular sites of functional cell cycle phospho-regulation we generated a synthetic cyclin-dependent kinase which can be recruited to any given GFP-tagged protein. Using this system with a set of proteins involved in chromosome segregation, we identified Mif2CENP-Cas a kinetochore target of CDK and show that CDK stabilises Mif2’s kinetochore localisation.
Enantiopure (S)-butan-2-yl N-(4-x-phenyl)thiocarbamates, x = NO2, OCH3, F, and Cl
Authors: Kaminsky Werner , Kaganyuk Max
Published: March 2023

The structures of (S)-butan-2-yl N-(4-nitrophenyl)thiocarbamate, C11H14N2O3S, (I), (S)-butan-2-yl N-(4-methoxyphenyl)thiocarbamate, C12H17NO2S, (II), (S)-butan-2-yl N-(4-fluorophenyl)thiocarbamate, C11H14FNOS, (III), and (S)-butan-2-yl N-(4-chlorophenyl)thiocarbamate, C11H14ClNOS, (IV), all at 100 K, have monoclinic (P21) symmetry with two independent molecules in the asymmetric unit. The Flack absolute structure parameters in all cases confirm the absence of inversion symmetry. The structures display N—H...S hydrogen bonds, resulting in R
2
2(8) hydrogen-bonded ring synthons connecting the two independent molecules. Despite the ring synthon, the packing follows two distinct patterns, with (I) and (IV) `pancaking' along the b-axis direction, while the other two `sandwich' in layers perpendicular to the b axis. Crystal morphologies were determined theoretically via the BFDH (Bravais, Friedel, Donnay–Harker) model and agree qualitatively with the experimentally indexed results. One of the butyl substituent of (II) exhibits structural disorder.
Conformational transition of the Ixodes ricinus salivary serpin Iripin-4
Authors: Kascakova Barbora , Kotal Jan , Havlickova Petra , Vopatkova Vera , Prudnikova Tatyana , Grinkevich Pavel , Kuty Michal , Chmelar Jindrich , Kuta Smatanova Ivana
Published: March 2023

Iripin-4, one of the many salivary serpins from Ixodes ricinus ticks with an as-yet unexplained function, crystallized in two different structural conformations, namely the native partially relaxed state and the cleaved serpin. The native structure was solved at a resolution of 2.3 Å and the structure of the cleaved conformation was solved at 2.0 Å resolution. Furthermore, structural changes were observed when the reactive-centre loop transitioned from the native conformation to the cleaved conformation. In addition to this finding, it was confirmed that Glu341 represents a primary substrate-recognition site for the inhibitory mechanism. The presence of glutamate instead of the typical arginine in the P1 recognition site of all structurally characterized I. ricinus serpins (PDB entries 7b2t, 7pmu and 7ahp), except for the tyrosine in the P1 site of Iripin-2 (formerly IRS-2; PDB entry 3nda), would explain the absence of inhibition of the tested proteases that cleave their substrate after arginine. Further research on Iripin-4 should focus on functional analysis of this interesting serpin.
Qualitative assessment of resilience in construction projects
Authors: Hilu Khalid A. , Hiyassat Mohammed A.
Published: March 2023

Purpose

Due to the recent increase in unexpected events that negatively affect projects, the concept of resilience has grasped the attention of researchers, as risk management alone fails to address unpredicted events. This study aims to identify resilience dimensions and their designated factors and then construct a comprehensive definition for resilience in construction projects.

Design/methodology/approach

This paper adopted a qualitative research design through content analysis of semi-structured interviews with project engineers on behalf of their construction project; 26 interviews were analyzed via ATLAS.ti.

Findings

The results demonstrate that resilience in construction projects consists of four main dimensions: preparation, absorption, recovery and adaptation; each dimension comprises separate factors. The evidence from this study demonstrates that the resilience of the organization, project team and project manager supports the construction project when facing unpredicted or abnormal conditions.

Practical implications

The results of this paper will help construction project managers to enhance the resilience of their projects by providing different resilience factors.

Originality/value

The resilience concept in projects is novel and has limited knowledge available, especially in construction projects therefore, it requires additional comprehensive discussion and validation. The findings of this paper will serve as a cornerstone for the development of the resilience field and enrich the indigent literature on resilience in the construction industry.
Leveraging socio-technical processes to support researchers
Authors: Smith II Plato L.
Published: March 2023

Purpose

The purpose of this project was to develop research support services that address local and external research data management (RDM) support drivers within the existing organizational culture at the University of Florida. The goal was to prompt organization change to support a campus-wide electronic lab notebook.

Design/methodology/approach

This project used a mixed-methods research approach to cultivate an organizational change program that support technological infrastructure to benefit researchers. The mixed-methods research involved participation action research integrated with a stakeholder approach.

Findings

The development of the grant proposal which was unfunded led to development of continued project goals. This project confirmed the development for support for an institution-wide electronic research notebook (ERN) solution requires adherence to the summary of five key actions for developing RDM services. Failure to complete all of the key actions engenders fragmentation culture.

Research limitations/implications

This project includes implications for institutions to develop grant proposals with integrated budgets for research support services of funded projects; and to use the summary of key actions for developing RDM services articulated by Jones et al. (2013) in “How to Develop RDM Services – a guide for HEIs.” Both are need to support findable, accessible, interoperable and reusable data for researchers.

Practical implications

This project has practical implications for higher education institutions interested in leveraging socio-technical processes to advance the role of libraries as collaborator, partner and stakeholder in developing institution-wide adoption, support and training for ERN as a research support service to RDM.

Social implications

This paper contributes to the body of developing literature on ERN as support services to RDM lead by academic research libraries.

Originality/value

This project contributed to the change in organization culture resulting in the successful collaboration between the Research Office and College of Medicine to support an institution-wide ERN technological infrastructure for one year as a pilot at a large academic research institution in the southeast USA.
The effect of co-patenting as a form of knowledge meta-integration on technological differentiation at Siemens
Authors: Ervits Irina
Published: March 2023

Purpose

The paper proposes an answer to one of the most important questions in corporate innovation management: what mechanisms of technological diversification exist within multinational companies? It is ascertained that research and development (R&D) intra-firm co-invention or co-patenting is one of those mechanisms. Co-invention implies knowledge-sharing, which should lead to unique combinations of knowledge and expertise and hence technological diversification of patent applications.

Design/methodology/approach

This paper offers a novel conceptual framework exploring the relationship between patents’ technological diversification and a detailed classification of different forms of international co-invention. Based on the case of Siemens’ Patent Cooperation Treaty (PCT) applications, the revealed technological advantage (RTA) index is utilized to measure the extent of the technological diversification of patent output.

Findings

The results show that patent applications generated by subsidiaries in advanced economies in cooperation with other subsidiaries feature unique technological areas that deviate from the company's overall technological specializations. These results provide a strong argument in favor of inter-subsidiary or horizontal co-patenting as a mechanism of new knowledge creation.

Research limitations/implications

On the conceptual level, the results accentuate inter-subsidiary patenting being an important mechanism of knowledge meta-integration boosting technological diversification. The obvious limitation of this paper lies in exploring a single company case, which restricts the generalizability of our findings. Due to the dynamic nature of technological change, the author’s dataset also suffers from a lack of temporal external validity. Future research can expand the scope in both regards in applying our co-invention mode typology.

Practical implications

Based on the results, to diversify knowledge portfolio, companies should strengthen the co-patenting effort and reinforce horizontal (inter-subsidiary) R&D collaborations.

Originality/value

To the author’s knowledge, this is the first time when such a nuanced typology of co-invention modes is being utilized to understand the effect of different co-invention categories on knowledge diversification.
Adoption of service robots: exploring the emerging trends through the lens of bibliometric analysis
Authors: Madhan Kumar , Shagirbasha Shameem , Kumar Mishra Tanmaya , Iqbal Juman
Published: March 2023

Purpose

The aim of this study is to examine the existing literature on service robots in order to identify prominent themes, assess the present state of service robotics research and highlight the contributions of seminal publications in the business, management and hospitality domain.

Design/methodology/approach

This study analysed 332 Scopus papers from 1985 to 2022 using bibliometric techniques like citation and co-citation analysis.

Findings

The study findings highlighted that there has been a consistent rise in publications related to service robots. The paper identifies three significant themes in the service robot literature: adoption of service robots in the context of customer service, anthropomorphism and integration of artificial intelligence in robotic service. Furthermore, this study highlights prominent authors, journals, institutions and countries associated with research on service robots and discusses the future research opportunities in this domain.

Originality/value

This study contributes to the service robots’ literature in the hospitality context by compilation of various reference materials using a comprehensive bibliometric analysis. Previous studies do not point out crucial themes in this area, nor do they provide an overview of prominent journals, institutions, authors and trends in this field. Therefore, this study attempts to fill the lacunae.
Quiet quitting: relationship with other concepts and implications for tourism and hospitality
Authors: Hamouche Salima , Koritos Christos , Papastathopoulos Avraam
Published: March 2023

Purpose

While quiet quitting is not an entirely new phenomenon, no published research has examined its relationship to existing concepts from a human resource management and organizational behavior perspective. Therefore, this study is a critical reflection that aims to demonstrate the relationship of quiet quitting with concepts researchers in tourism and hospitality have extensively used to study related phenomena.

Design/methodology/approach

Gray literature was mobilized to capture the momentum of this new phenomenon, whereas scholarly research was reviewed to identify existing concepts associated with quiet quitting and suggest directions for theory-building and empirical research.

Findings

In its contemporary form, quiet quitting mostly resonates with younger employees, due to the drastic changes in workplaces following the COVID-19 pandemic. While quiet quitting closely resembles collective industrial action such as “work to rule” and “acting one’s wage,” it also has a psychological dimension, and can be understood through concepts such as work withdrawal, employee cynicism, and silence. Multiple theories and concepts are proposed to facilitate the conceptualization and operationalization of quiet quitting (e.g. organizational citizenship behavior, social exchange, psychological contract, organizational justice, conflict theory, equity theory, two-factor theory, job demands-resources and conservation of resources theories).

Practical implications

This research provides practical suggestions to managers in tourism and hospitality to prevent the occurrence of quiet quitting in the first place, as well as effectively handling it once it occurs.

Originality/value

Studies addressing quiet quitting are rare. This paper attempts to synthesize diverse concepts and theories associated with quiet quitting to understand its meaning, potential causes and to suggest avenues for future research.
Quantile connectedness among real estate investment trusts during COVID-19: evidence from the extreme tails of distributions
Authors: Tong Hongxia , Khaskheli Asadullah , Masood Amna
Published: March 2023

Purpose

Given the evolving market integration, this study aims to explore the connectedness of 12 real estate investment trusts (REITs) during the COVID-19 period.

Design/methodology/approach

The connectedness of 12 REITs was examined by considering three sample periods: full period, COVID peak period and COVID recovery period by using the quantile vector autoregressive (VAR) approach.

Findings

The findings ascertain that REIT markets are sensitive to COVID, revealing significant connectedness during each sample period. The USA and The Netherlands are the major shock transmitters; thus, these countries are relatively better options for the predictive behavior of the rest of the REIT markets. In contrast, Hong Kong and Japan are the least favorable REIT markets with higher shock-receiving potential.

Research limitations/implications

The study recommends implications for real estate industry agents and investors to evaluate and anticipate the direction of return connectedness at each phase of the pandemic, such that they can incorporate those global REITs less vulnerable to unplanned crises. Apart from these implications, the study is limited to the global REIT markets and only focused on the period of COVID-19, excluding the concept of other financial and health crises.

Originality/value

This study uses a novel approach of the quantile-based VAR to determine the connectedness among REITs. Furthermore, the present work is a pioneer study because it is targeting different time periods of the pandemic. Additionally, the outcomes of the study are valuable for investors, policymakers and portfolio managers to formulate future development strategies and consolidate REITs during the period of crisis.
The common agricultural policy subsidies and the technical efficiency of Hungarian wine farms
Authors: Fertő Imre , Bojnec Štefan
Published: March 2023

Purpose

The literature argues on ambiguous impacts of different types of the common agricultural policy (CAP) subsidies on farm technical efficiency (TE). The purpose of this paper is to estimate and analyse the TE and the impact of the CAP subsidies on the TE of wine farms in Hungary using the farm accountancy data network data set in the period 2013–2019.

Design/methodology/approach

The authors use stochastic frontiers analysis (SFA) models to estimate the TE scores for the Hungarian wine farms with four wine farm-level inputs in terms of agricultural land, labour, capital and intermediate consumption. The TE scores are explained by the CAP subsidies and economic wine farm size. The different SFA models were applied with robustness tests to investigate the drivers of the TE values of wineries.

Findings

Like for Hungarian farms in general, the distribution of the wine farm structure is a dual with a greater number of smaller wine farms and a smaller number of bigger wine farms. The agricultural land, capital and intermediate consumption are significantly positively associated with the wine farm TE. With higher capital intensity wine farm TE increase. The results imply that the CAP subsidies decrease the TE of the Hungarian wine farms, whereas economic farm size increase.

Originality/value

To the best of the authors’ knowledge, this is one of the first specific efficiency studies on the wine sector in the Central and Eastern European region and the first one for Hungary to evaluate the TE at wine farm level and to assess the impact of CAP subsidies and economic farm size on wine farm (in)efficiency to apply production technologies and use farm resources. This study is among the first that applied the fixed-effects stochastic frontier model at the wine farm level to measure the drivers of the TE scores.
IKEA vs Trophy effect – an experimental comparison
Authors: Bühren Christoph , Pleßner Marco
Published: March 2023

Purpose

What if companies try to combine the IKEA and Trophy winner effects? The purpose of this study is to understand the similarities and differences between both effects. This is not only theoretically but also practically important for the way that companies interact with their customers.

Design/methodology/approach

Successful work – invested either to create or to obtain a product – increases the customers’ valuation of the product. This phenomenon known as the IKEA or Trophy winner effect. This study directly compares both effects using experiments with two different products (paper planes and 3D puzzles). Moreover, this study tests whether they reinforce each other.

Findings

The Trophy winner effect looms larger than the IKEA effect for inexpensive items. For slightly more expensive products, this study finds a Trophy loser effect. Positive emotions of trophy winners drive the results for inexpensive products, whereas negative emotions of trophy losers drive the results for slightly more expensive products.

Research limitations/implications

The relevance of the IKEA and Trophy effects is influenced by the type of product. Customers’ labor invested in the product itself is of greater importance the more expensive the product is. As soon as customers interpret the interaction with other customers as competition, the effect on valuation can be substantial even for inexpensive products. Future studies could try to replicate our results with different product categories.

Originality/value

Although the IKEA and Trophy effects are no new phenomena in consumer psychology and behavioral economics, they have not been compared to each other or combined yet. The results are useful for researchers and practitioners alike. They yield implications for product customization and customer empowerment.