bluuebunny/crossref_metadata_2025 huggingface dataset:
NNAL, a major metabolite of tobacco-specific carcinogen NNK, promotes lung cancer progression through deactivating LKB1 in an isomer-dependent manner
Authors: Bian Tengfei , Wang Yuzhi , Botello Jordy F. , Hu Qi , Jiang Yunhan , Zingone Adriana , Corral Pedro A. , Zahra Aly F. , Wu Yougen , Ryan Bríd M. , Jin Lingtao , Xing Chengguo
Published: June 2021

Smoking is associated with worse clinical outcomes for lung cancer patients. Cell-based studies suggest that NNK (a tobacco specific carcinogen) promotes lung cancer progression. Given its short half-life, the physiological relevance of these in vitro results remains elusive. NNAL, a major metabolite of NNK with a similar structure, a chiral center, and a longer half-life, has never been evaluated in cancer cells. In this study, we characterized the effect of NNAL and its enantiomers on cancer progression among a panel of NSCLC cell lines and explored the associated mechanisms. We found that (R)-NNAL promotes cell proliferation, enhances migration, and induces drug resistance while (S)-NNAL has much weaker effects. Mechanistically, (R)-NNAL phosphorylates and deactivates LKB1 via the β-AR signaling in the LKB1 wild type NSCLC cell lines, contributing to the enhanced proliferation, migration, and drug resistance. Of note, NNK exposure also increases the phosphorylation of LKB1 in A/J mice. More importantly, human lung cancer tissues appear to have elevated LKB1 phosphorylation. Our results reveal, for the first time, that NNAL may promote lung cancer progression through LKB1 deactivation in an isomer-dependent manner.
3D reconstruction identifies loci linked to variation in angle of individual sorghum leaves
Authors: Tross Michael C. , Gaillard Mathieu , Zweiner Mackenzie , Miao Chenyong , Grove Ryleigh J. , Li Bosheng , Benes Bedrich , Schnable James C.
Published: June 2021

Selection for yield at high planting density has reshaped the leaf canopy of maize, improving photosynthetic productivity in high density settings. Further optimization of canopy architecture may be possible. However, measuring leaf angles, the widely studied component trait of leaf canopy architecture, by hand is a labor and time intensive process. Here, we use multiple, calibrated, 2D images to reconstruct the 3D geometry of individual sorghum plants using a voxel carving based algorithm. Automatic skeletonization and segmentation of these 3D geometries enable quantification of the angle of each leaf for each plant. The resulting measurements are both heritable and correlated with manually collected leaf angles. This automated and scaleable reconstruction approach was employed to measure leaf-by-leaf angles for a population of 366 sorghum plants at multiple time points, resulting in 971 successful reconstructions and 3,376 leaf angle measurements from individual leaves. A genome wide association study conducted using aggregated leaf angle data identified a known large effect leaf angle gene, several previously identified leaf angle QTL from a sorghum NAM population, and novel signals. Genome wide association studies conducted separately for three individual sorghum leaves identified a number of the same signals, a previously unreported signal shared across multiple leaves, and signals near the sorghum orthologs of two maize genes known to influence leaf angle. Automated measurement of individual leaves and mapping variants associated with leaf angle reduce the barriers to engineering ideal canopy architectures in sorghum and other grain crops.
Deep Mutational Scanning of Dynamic Interaction Networks in the SARS-CoV-2 Spike Protein Complexes: Allosteric Hotspots Control Functional Mimicry and Resilience to Mutational Escape
Authors: Verkhivker Gennady M.
Published: June 2021

We develop a computational approach for deep mutational scanning of residue interaction networks in the SARS-CoV-2 spike protein complexes to characterize mechanisms of functional mimicry and resilience to mutational escape by miniprotein inhibitors. Using a dynamic mutational profiling and sensitivity analysis of protein stability, binding interactions and global network parameters describing allosteric signaling, we identify regulatory hotspots in the SARS-CoV-2 S complexes with the ACE2 host receptor and ultra-potent miniproteins. The results revealed that global circulating variants are associated with allosteric control points that are dynamically coupled to structural stability hotspots. In this mechanism, variant-induced perturbations of flexible allosteric sites can result in global network changes and elicit specific protein responses. The binding affinity fingerprints and allosteric signatures of the SARS-CoV-2 complexes with miniproteins are determined by a dynamic cross-talk between regulatory control points and conformationally adaptable allosteric hotspots that collectively control structure-functional mimicry, signal transmission and resilience to mutational escape.
Comprehensive Phenotyping of Cutaneous Afferents Reveals Rapid-Onset Alterations in Nociceptor Response Properties Following Spinal Cord Injury
Authors: Eller Olivia C. , Stair Rena N. , Neal Christopher , Rowe Peter S. N. , Nelson-Brantley Jennifer , Young Erin E. , Baumbauer Kyle M.
Published: June 2021

Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Here we demonstrate that thoracic spinal contusion injury results in the emergence of autotomy and spasticity, both indicators of spontaneous pain, in areas below the level of the injury within 24 hr of SCI. These behaviors were associated with hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration. Electrophysiological recordings using an ex vivo skin/nerve/DRG/spinal cord preparation demonstrated that SCI increased mechanical and thermal sensitivity, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low thermal thresholds, while AD was found more frequently in nociceptors with high thermal thresholds. These results demonstrate that SCI causes the rapid-onset of peripheral inflammation-like processes that sensitize nociceptors, which may contribute to the early emergence and persistence of chronic SCI pain.
GIP: An open-source computational pipeline for mapping genomic instability from protists to cancer cells
Authors: Späth Gerald F. , Bussotti Giovanni
Published: June 2021

Genome instability has been recognized as a key driver for microbial and cancer adaptation and thus plays a central role in many human pathologies. Even though genome instability encompasses different types of genomic alterations, most available genome analysis software are limited to just one kind mutation or analytical step. To overcome this limitation and better understand the role of genetic changes in enhancing pathogenicity we established GIP, a novel, powerful bioinformatic pipeline for comparative genome analysis. Here we show its application to whole genome sequencing datasets ofLeishmania,Plasmodium, Candida, and cancer. Applying GIP on available data sets validated our pipeline and demonstrated the power of our analysis tool to drive biological discovery. Applied toPlasmodium vivaxgenomes, our pipeline allowed us to uncover the convergent amplification of erythrocyte binding proteins and to identify a nullisomic strain. Re-analyzing genomes of drug adaptedCandida albicansstrains revealed correlated copy number variations of functionally related genes, strongly supporting a mechanism of epistatic adaptation through interacting gene-dosage changes. Our results illustrate how GIP can be used for the identification of aneuploidy, gene copy number variations, changes in nucleic acid sequences, and chromosomal rearrangements. Altogether, GIP can shed light on the genetic bases of cell adaptation and drive disease biomarker discovery.

One Sentence Summary

GIP - a novel pipeline for detecting, comparing and visualizing genome instability.
Atlantic salmon farms are a likely source of Tenacibaculum maritimum infection in migratory Fraser River sockeye salmon
Authors: Bateman Andrew W. , Teffer Amy K. , Bass Arthur , Ming Tobi , Hunt Brian P. V. , Krkošek Martin , Miller Kristina M.
Published: June 2021

Infectious disease from domestic hosts, held for agriculture, can impact wild species that migrate in close proximity, potentially reversing selective advantages afforded by migration. For sockeye salmon in British Columbia, Canada, juveniles migrate past numerous Atlantic salmon farms from which they may acquire a number of infectious agents. We analyse patterns of molecular detection in juvenile sockeye salmon for one bacterial pathogen, Tenacibaculum maritimum, known to cause disease in fish species around the globe and to cause mouthrot disease in farmed Atlantic salmon in BC. Our data show a clear peak in T. maritimum detections in the Discovery Islands region of BC, where sockeye migrate close to salmon farms. Using well established differential-equation models to describe sockeye migration and T. maritimum infection spread, we fit models to our detection data to assess support for multiple hypotheses describing farm- and background-origin infection. Despite a data-constrained inability to resolve certain epidemiological features of the system, such as the relative roles of post infection mortality and recovery, our models clearly support the role of Discovery-Islands salmon farms in producing the observed patterns. Our best models (with 99.8% empirical model support) describe relatively constant (background) infection pressure, except around Discovery-Islands salmon farms, where farm-origin infection pressure peaked at 12.7 (approximate 95% CI: 4.5 to 31) times background levels. Given the evidence for farm-origin transfer of T. maritimum to Fraser-River sockeye salmon, the severity of associated disease in related species, and the imperilled nature of Fraser River sockeye generally, our results suggest the need for a more precautionary approach to managing farm/wild interactions in sockeye salmon.
Structural Modeling of the TMPRSS Subfamily of Host Cell Proteases Reveals Potential Binding Sites
Authors: Escalante Diego E. , Wang Austin , Ferguson David M.
Published: June 2021

The transmembrane protease serine subfamily (TMPRSS) has at least eight members with known protein sequence: TMPRSS2, TMPRRS3, TMPRSS4, TMPRSS5, TMPRSS6, TMPRSS7, TMPRSS9, TMPRSS11, TMPRSS12 and TMPRSS13. A majority of these TMPRSS proteins have key roles in human hemostasis as well as promoting certain pathologies, including several types of cancer. In addition, TMPRSS proteins have been shown to facilitate the entrance of respiratory viruses into human cells, most notably TMPRSS2 and TMPRSS4 activate the spike protein of the SARS-CoV-2 virus. Despite the wide range of functions that these proteins have in the human body, none of them have been successfully crystallized. The lack of structural data has significantly hindered any efforts to identify potential drug candidates with high selectivity to these proteins. In this study, we present homology models for all members of the TMPRSS family including any known isoform (the homology model of TMPRSS2 is not included in this study as it has been previously published). The atomic coordinates for all homology models have been refined and equilibrated through molecular dynamic simulations. The structural data revealed potential binding sites for all TMPRSS as well as key amino acids that can be targeted for drug selectivity.
Extracellular RNA moves from the glomerulus to the renal tubule
Authors: Hunter Robert W , Kumar Sujai , Coward Richard JM , Buck Amy H , Dear James W
Published: June 2021

There is a wealth of indirect evidence that extracellular RNA (exRNA) signalling can regulate renal tubular epithelial cell function. However, the physiological importance of this signalling is uncertain. We sought to determine the extent of extracellular RNA transfer between cells in a healthy kidney. We tested the hypothesis that RNA travels from glomerular podocytes to renal tubular epithelial cells.

We developed a method to track exRNA in the kidney using SLAMseq (SH-linked alkylation for the metabolic sequencing of RNA in tissue). We crossed podocin-Cre mice with floxed-stop-UPRT mice to express recombinant uracil phosphoribosyl transferase (UPRT) in podocytes. Mice were injected with the modified nucleobase 4-thiouracil, which is incorporated into nascent RNA with high efficiency only in UPRT-expressing cells. We harvested glomeruli or tubular cells, extracted RNA and prepared libraries for SLAMseq, in which sites of mRNA labelling with 4-thiouracil are detected as T>C conversions in 3’UTRs.

In glomeruli, we detected labelling of known podocyte genes but not of genes known to be restricted to endothelial, renal tubular or white blood cells. Setting a false-discovery rate of 1%, the proportion of genes deemed to be labelled with high confidence was 7.1% (95% confidence interval 6.8 – 7.4%) in 4TU-treated podocyte-UPRT mice, 2.5% (2.3 – 2.7%) in Cre-negative controls and 1.0% (0.9 – 1.1%) in 4TU-naïve controls.

In tubular cells, we detected a small but statistically significant increase in RNA labelling in podocyte-UPRT mice compared to Cre-negative controls (p = 7.4 × 10−16 in a zero-inflated Poisson regression model). We conclude that RNA is transferred from podocytes to renal tubular epithelial cells in vivo under physiological conditions. Our model provides the opportunity to explore the consequences of this novel signalling pathway in health and kidney disease.
Fungi anaesthesia
Authors: Adamatzky Andrew , Gandia Antoni
Published: June 2021

Electrical activity of fungus Pleurotus ostreatus is characterised by slow (hours) irregular waves of baseline potential drift and fast (minutes) action potential likes spikes of the electrical potential. An exposure of the mycelium colonised substrate to a chloroform vapour lead to several fold decrease of the baseline potential waves and increase of their duration. The chloroform vapour also causes either complete cessation of spiking activity or substantial reduction of the spiking frequency. Removal of the chloroform vapour from the growth containers leads to a gradual restoration of the mycelium electrical activity.
SARS-CoV-2 Viral Replication in a High Throughput Human Primary Epithelial Airway Organ Model
Authors: Fisher Christine R. , Medie Felix Mba , Luu Rebeccah J. , Gaibler Robert , Miller Caitlin R. , Mulhern Thomas J. , Vijayakumar Vidhya , Marr Elizabeth , Alladina Jehan , Medoff Benjamin , Borenstein Jeffrey T. , Gard Ashley L.
Published: June 2021

COVID-19 emerged as a worldwide pandemic early in 2020, and at this writing has caused over 170 million cases and 3.7 million deaths worldwide, and almost 600,000 deaths in the United States. The rapid development of several safe and highly efficacious vaccines stands as one of the most extraordinary achievements in modern medicine, but the identification and administration of efficacious therapeutics to treat patients suffering from COVID-19 has been far less successful. A major factor limiting progress in the development of effective treatments has been a lack of suitable preclinical models for the disease, currently reliant upon various animal models and in vitro culture of immortalized cell lines. Here we report the first successful demonstration of SARS-CoV-2 infection and viral replication in a human primary cell-based organ-on-chip, leveraging a recently developed tissue culture platform known as PREDICT96. This successful demonstration of SARS-CoV-2 infection in human primary airway epithelial cells derived from a living donor represents a powerful new pathway for disease modeling and an avenue for screening therapeutic candidates in a high throughput platform.
Systematic dissection of a complex gut bacterial community
Authors: Cheng Alice G. , Aranda-Díaz Andrés , Jain Sunit , Yu Feiqiao , Iakiviak Mikhail , Meng Xiandong , Weakley Allison , Patil Advait , Shiver Anthony L. , Deutschbauer Adam , Neff Norma , Huang Kerwyn Casey , Fischbach Michael A.
Published: June 2021

Efforts to model the gut microbiome have yielded important insights into the mechanisms of interspecies interactions, the impact of priority effects on ecosystem dynamics, and the role of diet and nutrient availability in determining community composition. However, the model communities studied to date have been defined or complex but not both, limiting their utility. Here, we construct a defined community of 104 bacterial strains composed of the most common taxa from the human gut microbiota. By propagating this community in growth media missing one amino acid at a time, we show that branched-chain amino acids have an outsize impact on community structure and identify a pathway in Clostridium sporogenes for generating ATP from arginine. We constructed and propagated the complete set of single-strain dropout communities, revealing a sparse network of strain-strain interactions including a novel interaction between C. sporogenes and Lactococcus lactis driven by metabolism. This work forms a foundation for studying strain-strain and strain-nutrient interactions in highly complex defined communities, and it provides a starting point for interrogating the rules of synthetic ecology at the 100+ strain scale.
Sirtuin 5 levels are limiting in preserving cardiac function and suppressing fibrosis in response to pressure overload
Authors: Guo Angela H. , Baliira Rachael K. , Skinner Mary E. , Kumar Surinder , Andren Anthony , Zhang Li , Michan Shaday , Davis Norma J. , Maccani Merissa W. , Day Sharlene M. , Sinclair David A. , Lyssiotis Costas A. , Stein Adam B. , Lombard David B.
Published: June 2021

Heart failure (HF) is defined as an inability of the heart to pump blood adequately to meet the body’s metabolic demands. HF with reduced systolic function is characterized by cardiac hypertrophy, ventricular fibrosis and remodeling, and decreased cardiac contractility, leading to cardiac functional impairment and death. Transverse aortic constriction (TAC) is a well-established model for inducing hypertrophy and HF in rodents. Mice globally deficient in sirtuin 5 (SIRT5), a NAD+-dependent deacylase, are hypersensitive to cardiac stress and display increased mortality after TAC. Prior studies assessing SIRT5 functions in the heart have all employed loss-of-function approaches. In this study, we generated SIRT5 overexpressing (SIRT5OE) mice, and evaluated their response to chronic pressure overload induced by TAC. Compared to littermate controls, SIRT5OE mice were protected from left ventricular dilation and impaired ejection fraction, adverse functional consequences of TAC. Transcriptomic analyses revealed that SIRT5 suppresses key HF sequelae, including the metabolic switch from fatty acid oxidation to glycolysis, immune activation, and increased fibrotic signaling. We conclude that SIRT5 is a limiting factor in the preservation of cardiac function in response to experimental pressure overload.
Multiple RSV strains infecting HEp-2 and A549 cells reveal cell line-dependent differences in resistance to RSV infection
Authors: Rajan Anubama , Piedra Felipe-Andrés , Aideyan Letisha , McBride Trevor , Robertson Matthew , Johnson Hannah L. , Aloisio Gina Marie , Henke David , Coarfa Cristian , Stossi Fabio , Menon Vipin Kumar , Doddapaneni Harshavardhan , Muzny Donna Marie , Cregeen Sara Joan Javornik , Hoffman Kristi Louise , Petrosino Joseph , Gibbs Richard A , Avadhanula Vasanthi , Piedra Pedro A.
Published: June 2021

Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat RSV disease. A few transformed cell lines and two historic strains have been extensively used to study RSV. Here we report a thorough molecular and cell biological characterization of HEp-2 and A549 cells infected with four strains of RSV representing both major subgroups as well as historic and more contemporaneous genotypes -- [RSV/A/Tracy (GA1), RSV/A/Ontario (ON), RSV/B/18537 (GB1), RSV/B/Buenos Aires (BA)] -- via measurements of viral replication kinetics and viral gene expression, immunofluorescence-based imaging of gross cellular morphology and cell-associated RSV, and measurements of host response including transcriptional changes and levels of secreted cytokines and growth factors. Our findings strongly suggest 1) the existence of a conserved difference in gene expression between RSV subgroups A and B; 2) the A549 cell line is a more stringent and natural host of replicating RSV than the HEp-2 cell line; and 3) consistent with previous studies, determining the full effects of viral genetic variation in RSV pathogenesis requires model systems as tractable as transformed cell lines but better representative of the human host.

IMPORTANCE

Infection with respiratory syncytial virus (RSV) early in life is essentially guaranteed and can lead to severe disease. In vitro data from two historic RSV/A strains and two cell lines, HEp-2 and A549, constitute most of our knowledge; but RSV contains ample variation from two evolving subgroups (A and B) showing recent convergent evolution. Here we measure viral action and host response in HEp-2 and A549 cells infected with four RSV strains from both subgroups and representing both historic and more contemporaneous strains. We discover a subgroup-dependent difference in viral gene expression and find A549 cells are more potently antiviral and more sensitive, albeit subtly, to viral variation. Our findings reveal important differences between RSV subgroups and two widely used cell lines and provide baseline data for experiments with model systems better representative of natural RSV infection.
The microtubule plus-end tracking protein Bik1 is required for chromosome congression
Authors: Julner Alexander , Abbasi Marjan , Menéndez-Benito Victoria
Published: June 2021

During mitosis, sister chromatids congress on both sides of the spindle equator to facilitate the correct partitioning of the genomic material. Chromosome congression requires a finely tuned control of microtubule dynamics by the kinesin motor proteins. In Saccharomyces cerevisiae, the kinesin proteins Cin8, Kip1, and Kip3 have a pivotal role in chromosome congression. It has been hypothesized that additional proteins that modulate microtubule dynamics are also involved. Here, we show that the microtubule plus-end tracking protein Bik1 – the budding yeast ortholog of CLIP-170 – is essential for chromosome congression. We find that nuclear Bik1 localizes to the kinetochores in a cell-cycle-dependent manner. Disrupting the nuclear pool of Bik1 with a nuclear export signal (Bik1-NES) leads to a slower cell cycle progression characterized by a delayed metaphase-anaphase transition. Bik1-NES cells have mispositioned kinetochores along the spindle in metaphase. Furthermore, using proximity-dependent methods, we identify Cin8 as an interaction partner of Bik1. Deleting CIN8 reduces the amount of Bik1 at the spindle. In contrast, Cin8 retains its typical bilobed distribution in the Bik1-NES mutant and does not localize to the unclustered kinetochores. Thus, we propose that Bik1 functions with Cin8 to regulate kinetochore-microtubule dynamics for correct kinetochore positioning and chromosome congression.
The Association Between Poor Sleep and Accelerated Brain Ageing
Authors: Ramduny Jivesh , Bastiani Matteo , Huedepohl Robin , Sotiropoulos Stamatios N. , Chechlacz Magdalena
Published: June 2021

The ageing brain undergoes widespread gray (GM) and white matter (WM) degeneration. But numerous studies indicate large heterogeneity in the age-related brain changes, which can be attributed to modifiable lifestyle factors, including sleep. Inadequate sleep has been previously linked to GM atrophy and WM changes. However, the reported findings are highly inconsistent. By contrast to previous research independently characterizing patterns of either the GM or the WM changes, we used here linked independent component analysis (FLICA) to examine covariation in GM and WM in a group of older adults. Next, we employed a novel technique to estimate the brain age delta (i.e. difference between chronological and apparent brain age assessed using neuroimaging data) and study its associations with sleep quality and sleep fragmentation, hypothesizing that poor sleep accelerates brain ageing. FLICA revealed a number of multimodal (including both GM and WM) neuroimaging components, associated with age, but also with sleep quality and sleep fragmentation. Brain age delta estimates were highly sensitive in detecting the effects of sleep problems on the ageing brain. Specifically, we show significant associations between brain age delta and poor sleep quality, suggesting two years deviation above the chronological age. Our findings indicate that sleep problems in healthy older adults should be considered a risk factor for accelerated brain ageing.
A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters
Authors: Wuertz Kathryn McGuckin , Barkei Erica K. , Chen Wei-Hung , Martinez Elizabeth J. , Lakhal-Naouar Ines , Jagodzinski Linda L. , Paquin-Proulx Dominic , Gromowski Gregory D. , Swafford Isabella , Ganesh Akshaya , Dong Ming , Zeng Xiankun , Thomas Paul V. , Sankhala Rajeshwer S. , Hajduczki Agnes , Peterson Caroline E. , Kuklis Caitlin , Soman Sandrine , Wieczorek Lindsay , Zemil Michelle , Anderson Alexander , Darden Janice , Hernandez Heather , Grove Hannah , Dussupt Vincent , Hack Holly , de la Barrera Rafael , Zarling Stasya , Wood James F. , Froude Jeffrey W. , Gagne Matthew , Henry Amy R. , Mokhtari Elham Bayat , Mudvari Prakriti , Krebs Shelly J. , Pekosz Andrew S. , Currier Jeffrey R. , Kar Swagata , Porto Maciel , Winn Adrienne , Radzyminski Kamil , Lewis Mark G. , Vasan Sandhya , Suthar Mehul , Polonis Victoria R. , Matyas Gary R. , Boritz Eli A. , Douek Daniel C. , Seder Robert A. , Daye Sharon P. , Rao Mangala , Peel Sheila A. , Gordon Joyce M. , Bolton Diane L. , Michael Nelson L. , Modjarrad Kayvon
Published: June 2021

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.
ultraID: a compact and efficient enzyme for proximity-dependent biotinylation in living cells
Authors: Zhao Xiyan , Bitsch Sebastian , Kubitz Lea , Schmitt Kerstin , Deweid Lukas , Roehrig Amélie , Barazzone Elisa Cappio , Valerius Oliver , Kolmar Harald , Béthune Julien
Published: June 2021

Proximity-dependent biotinylation (PDB) combined with mass spectrometry analysis has established itself as a key technology to study protein-protein interactions in living cells. A widespread approach, BioID, uses an abortive variant of theE. coliBirA biotin protein ligase, a quite bulky enzyme with slow labeling kinetics. To improve PDB versatility and speed, various enzymes have been developed by different approaches. Here we present a novel small-size engineered enzyme: ultraID. We show its practical use to probe the interactome of Argonaute-2 after a 10 min labeling pulse and expression at physiological levels. Moreover, using ultraID, we provide a membrane-associated interactome of coatomer, the coat protein complex of COPI vesicles. To date, ultraID is the smallest and most efficient biotin ligase available for PDB and offers the possibility of investigating interactomes at a high temporal resolution.
Topological digestion drives time-varying rheology of entangled DNA fluids
Authors: Michieletto D. , Neill P. , Weir S. , Evans D. , Crist N. , Martinez V. A. , Robertson-Anderson R. M.
Published: June 2021

Understanding and controlling the rheology of polymeric complex fluids that are pushed out-of-equilibrium is a fundamental problem in both industry and biology. For example, to package, repair, and replicate DNA, cells use enzymes to constantly manipulate DNA topology, length, and structure. Inspired by this, here we engineer and study DNA-based complex fluids that undergo enzymatically-driven topological and architectural alterations via restriction endonuclease (RE) reactions. We show that these systems display time-dependent rheological properties that depend on the concentrations and properties of the comprising DNA and REs. Through time-resolved microrheology experiments and Brownian Dynamics simulations, we show that conversion of supercoiled to linear DNA topology leads to a monotonic increase in viscosity. On the other hand, the viscosity of entangled linear DNA undergoing fragmentation displays a universal decrease that we rationalize using living polymer theory. Finally, to showcase the tunability of these behaviours, we design a DNA fluid that exhibits a time-dependent increase, followed by a temporally-gated decrease, of its viscosity. Our results present a class of polymeric fluids that leverage naturally occurring enzymes to drive diverse time-varying rheology by performing architectural alterations to the constituents.
Prediction of biological age by morphological staging of sarcopenia inCaenorhabditis elegans
Authors: Dhondt Ineke , Verschuuren Clara , Zečić Aleksandra , Loier Tim , Braeckman Bart P. , De Vos Winnok H.
Published: June 2021

Sarcopenia encompasses a progressive decline in allover muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the strong commonalities with human muscle structure and the facile visualization possibilities,C. elegansrepresents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical assessment relies on visual scoring of muscle architecture, which is subjective and inaccurate. To resolve this, we have developed an automated image analysis pipeline for the detailed quantification and classification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter strains. We then extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed us to establish a general linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted RNAi-mediated knockdown of thedaf-2gene. We conclude that quantitative microscopy allows for staging sarcopenia inC. elegansand will be of use for systematic screening for pharmacological or genetic modulators that mitigate age-related muscle frailty and thus improve healthspan inC. elegans.
Study of naphthopyran derivatives: structure and photochromic properties in solution and in polymer film
Authors: Shi Linqi , Sun Zipei , Tian Jiajie , Huang Yaodong , Meng Jiben
Published: June 2021

Four naphthopyran derivatives, namely, 3,3-bis(naphthalen-1-yl)-3H-naphtho[2,1-b]pyran, C33H22O, NP1, 3,3-bis([1,1′-biphenyl]-4-yl)-3H-naphtho[2,1-b]pyran, C37H26O, NP2, 3,3-bis(4-phenoxyphenyl)-3H-naphtho[2,1-b]pyran, C37H26O2, NP3, and 3,3-bis(4-methoxy-2-methylphenyl)-3H-naphtho[2,1-b]pyran, C29H26O3, NP4, were synthesized and their photochromic properties investigated. NP1–NP4 exhibited good photochromism in different solutions and in poly(methyl methacrylate) (PMMA) film under UV light irradiation. Solvatochromism and the electronic and steric effects of the substituent group on photochromism were analyzed and decolouration curves were found to fit a monoexponential kinetic decay in most cases. Single-crystal X-ray analysis of NP1 and NP2 revealed the structure–property relationships. Good fatigue resistance of NP1, both in solution and in the PMMA film, endows it with potential value for applications.
On symmetry breaking of dual polyhedra of non-crystallographic group H
3
Authors: Myronova Mariia
Published: June 2021

The study of the polyhedra described in this paper is relevant to the icosahedral symmetry in the assembly of various spherical molecules, biomolecules and viruses. A symmetry-breaking mechanism is applied to the family of polytopes {\cal V}_{H_{3}}(\lambda) constructed for each type of dominant point λ. Here a polytope {\cal V}_{H_{3}}(\lambda) is considered as a dual of a {\cal D}_{H_{3}}(\lambda) polytope obtained from the action of the Coxeter group H
3 on a single point \lambda\in{\bb R}^{3}. The H
3 symmetry is reduced to the symmetry of its two-dimensional subgroups H
2, A
1 × A
1 and A
2 that are used to examine the geometric structure of {\cal V}_{H_{3}}(\lambda) polytopes. The latter is presented as a stack of parallel circular/polygonal orbits known as the `pancake' structure of a polytope. Inserting more orbits into an orbit decomposition results in the extension of the {\cal V}_{H_{3}}(\lambda) structure into various nanotubes. Moreover, since a {\cal V}_{H_{3}}(\lambda) polytope may contain the orbits obtained by the action of H
3 on the seed points (a, 0, 0), (0, b, 0) and (0, 0, c) within its structure, the stellations of flat-faced {\cal V}_{H_{3}}(\lambda) polytopes are constructed whenever the radii of such orbits are appropriately scaled. Finally, since the fullerene C20 has the dodecahedral structure of {\cal V}_{H_{3}}(a,0,0), the construction of the smallest fullerenes C24, C26, C28, C30 together with the nanotubes C20+6N
, C20+10N
is presented.
The “accountant” stereotype in the Florentine medieval popular culture: “galantuomini” or usurers?
Authors: Carungu Jonida , Molinari Matteo
Published: June 2021

Purpose

This paper explores the stereotype of the accountant in Florentine medieval popular culture based on literary works and from a historical perspective. It aims to highlight how stereotypes change with time and represent the cultural and historical evolution of a society. This research challenges Miley and Read (2012), who stated that the foundation of the stereotype was in Commedia dell'arte, an Italian form of improvisational theatre commenced in the 15th century.

Design/methodology/approach

The authors applied a qualitative research method to examine the accountant from a medieval popular culture perspective. The analysis consists of two phases: (1) categorisation of the accountant stereotype based on accounting history literature and (2) thematic analysis of The Divine Comedy (1307–1313) and The Decameron (1348–1351). The authors explored a synchronic perspective of historical investigation through a “cross-author” comparison, identifying Dante Alighieri as the first key author of medieval popular culture. During his imaginary journey through The Divine Comedy, Dante describes the social, political and economic context of the Florentine people of the 14th century. Then, with its various folkloristic elements, The Decameron of Giovanni Boccaccio becomes the “manifesto” of the popular culture in the Florentine medieval times.

Findings

This study shows the change of the accountant stereotype from the medieval age to the Renaissance. The Divine Comedy mainly connotes a negative accountant stereotype. The 14th century's Florentine gentlemen (“i galantuomini”) are apparently positive characters, with an ordered and clean aspect, but they are accused of being usurers. Dante Alighieri pictures the accountant as a “servant of capitalism”, “dishonest person, excessively fixated with money”, “villain and evil” and “excessively rational”. Giovanni Boccaccio mainly portrays a positive accountant stereotype. The accountant is increasingly more reliable, and this “commercial man” takes a more prestigious role in the society. In The Decameron, the accountant is depicted as a “hero”, “gentleman”, “family-oriented person with a high level of work commitment” and “colourful persona, warm, and emotional”. Overall, the authors provided new evidence on the existence of the accountant stereotype in the Florentine medieval popular.

Originality/value

This study engages with accounting history literature accountants' stereotypes in an unexplored context and time period, providing a base for comparative international research on accounting stereotypes and popular culture. Additionally, it addresses the need for further research on the accountant stereotype based on literary works and from a historical perspective. Therefore, this research also expands the New Accounting History (NAH) literature, focussing on the investigation of the accountant stereotype connotations in the 14th century.
Canola and olive oil gelled emulsions as pork fat replacers in beef burgers
Authors: Dias Maiara Fonseca , Guimarães Angélica Sousa , Benevenuto Júnior Augusto Aloísio , Silva Vanessa Riani Olmi , Fontes Paulo Rogério , Ramos Alcinéia de Lemos Souza , Ramos Eduardo Mendes
Published: June 2021

Purpose

To meet the consumer demand for a healthier diet, this study emphasizes the feasibility of using vegetable oil gelled emulsions in low-fat industrialized burgers with high contents of polyunsaturated fatty acids (PUFAS). Commercial canola and olive oils have been tested as a relatively inexpensive source of PUFAS.

Design/methodology/approach

Beef burgers were reformulated by replacing (0, 25, 50, 75 and 100%) pork back-fat with two carrageenan gelled emulsions of vegetable oils (canola and olive oil). The technological characteristics, sensorial properties and the fatty acid profile of reformulated burgers were evaluated.

Findings

Moisture content and cooking loss increased and fat and protein contents reduced with higher replacements. Oxidative stability was not affected and replacements of up to 75% did not affect the burger's acceptance. A total fat content reduction of 40% was achieved in burgers with 100% back-fat replacement, improving its nutrient value by increasing the ω−6/ω−3 ratio and decreasing the saturated fatty acids content (in 47%) and the atherogenic (from 0.61 to 0.22) and thrombogenic (from 1.29 to 0.65) indexes. Replacing up to 75% with canola oil gelled emulsion is a promising approach in the design of healthier industrial low-fat burgers.

Originality/value

Due to the association of some diseases with the consumption of products rich in saturated fat, the industry looks for alternatives not only to reduce the fat content but also to modify the fatty acid profile in meat products. This study further confirms the possibility of using carrageenan gelled fat replacer in industrialized burgers formulated with meat and other ingredients/additives commonly used to provide economic benefit. Also, confirms the feasibility to use commercial vegetable oils with relatively cheap cost than ω−3 rich oils as the oil phase in the gelled emulsion.
Can the media breed CEO overconfidence? A sociocognitive perspective in the Chinese context
Authors: Ji Yang , Zhou Erhua , Guo Wenbo
Published: June 2021

Purpose

Anchored in the role of a social arbiter, the purpose of this study is to examine whether and how media coverage has an impact on CEO overconfidence and further explore how media ownership and Confucianism affect the relationship in the Chinese context.

Design/methodology/approach

Using a sample of 1,492 Chinese listed companies from 2010 to 2015, the study adopts random effects models to empirically analyze the effect of media coverage on CEO overconfidence and the roles of media ownership and Confucianism.

Findings

The paper finds that media coverage is significantly and positively associated with CEO overconfidence, and the positive relationship between media coverage and CEO overconfidence becomes stronger for state-controlled media. What is more, the influence of media coverage on CEO overconfidence is attenuated for those firms located in stronger Confucianism atmosphere. A further analysis reveals that different tenors of media coverage yield asymmetric effects.

Originality/value

The paper provides a new and solid support for the argument that media praise stimulates CEO overconfidence and increases the knowledge about under what conditions CEO overconfidence varies, broadly speaking which fosters the development of upper echelons theory (UET). Meanwhile, the results extend the literature on media effect and information processing. The findings are also beneficial to improve corporate decisions and government regulation on Chinese media systems.
The efficiency of the Italian preventive agreement: a legal, economic and organizational perspective
Authors: Paletta Angelo , Alimehmeti Genc
Published: June 2021

Purpose

This paper aims to analyze the ex ante and ex post economic efficiency of the preventive agreement (concordato preventivo) or composition with creditors as defined by the Italian Bankruptcy Law. This study examines four possible outcomes of the procedure: homologation (confirmation); the degree of dissent/consent of creditors; the revocation, admissibility or inadmissibility; the declaration of the company bankruptcy in preventive agreement.

Design/methodology/approach

This paper uses data from 728 Italian companies which filed for preventive agreement in 2016. In reference to each of the four possible outcomes, this study applies nine logit regressions to analyze the effects of a series of efficiency variables ex ante (corporate-based drivers) and ex post (procedure-based drivers).

Findings

Results show the relevance of the debt structure, ownership structure and virtuous behavior, corporate governance and management systems, as well as effectivity of the court control on the preventive agreement outcome.

Originality/value

This paper draws on original data of bankruptcy in Italy and gives empirical evidence of the ex ante and ex post factors on the outcomes of the preventive agreement.
Artificial intelligence and human rights: a comprehensive study from Indian legal and policy perspective
Authors: Chatterjee Sheshadri , N.S. Sreenivasulu
Published: June 2021

Purpose

The purpose of this study is to investigate the impact of artificial intelligence (AI) on the human rights issue. This study has also examined issues with AI for business and its civil and criminal liability. This study has provided inputs to the policymakers and government authorities to overcome different challenges.

Design/methodology/approach

This study has analysed different international and Indian laws on human rights issues and the impacts of these laws to protect the human rights of the individual, which could be under threat due to the advancement of AI technology. This study has used descriptive doctrinal legal research methods to examine and understand the insights of existing laws and regulations in India to protect human rights and how these laws could be further developed to protect human rights under the Indian jurisprudence, which is under threat due to rapid advancement of AI-related technology.

Findings

The study provides a comprehensive insight on the influence of AI on human rights issues and the existing laws in India. The study also shows different policy initiatives by the Government of India to regulate AI.

Research limitations/implications

The study highlights some of the key policy recommendations helpful to regulate AI. Moreover, this study provides inputs to the regulatory authorities and legal fraternity to draft a much-needed comprehensive policy to regulate AI in the context of the protection of human rights of the citizens.

Originality/value

AI is constantly posing entangled challenges to human rights. There is no comprehensive study, which investigated the emergence of AI and its influence on human rights issues, especially from the Indian legal perspective. So there is a research gap. This study provides a unique insight of the emergence of AI applications and its influence on human rights issues and provides inputs to the policymaker to help them to draft an effective regulation on AI to protect the human rights of Indian citizens. Thus, this study is considered a unique study that adds value towards the overall literature.
Opportunities and risks of artificial intelligence in recruitment and selection
Authors: Ore Olajide , Sposato Martin
Published: June 2021

Purpose

The purpose of this study is to contribute to the knowledge on the opportunities and risks in the use of artificial intelligence (AI) in recruitment and selection by exploring the perspectives of recruitment professionals in a multicultural multinational organisation.

Design/methodology/approach

A qualitative approach was used in this exploratory study. Face-to-face, semi-structured in-depth interviews were conducted with ten professional recruiters who worked for a multinational corporation.

Findings

The findings revealed that AI facilitates the effective performance of routine tasks through automation. However, the adoption of AI technology in recruitment and selection is also fraught with risks that engender fear and distrust among recruiters. The effective adoption of AI can improve recruitment strategies. However, cynicism exists because of the fears of job losses to automation, even though the participants thought that their jobs would continue to exist because recruiters should always be humans.

Originality/value

This paper provides a unique exploration of the opportunities and risks in the adoption of AI for the recruitment and selection function in human resource management. The benefits are the delegation of routine tasks to AI and the confirmation of the crucial role of professional recruiters.
Research on innovative reinforcement of prestressed T-beam bridge
Authors: Zhang Kexin , Tianyu Qi , Dachao Li , Xingwei Xue , Wu Fayue , Liu Xinfeng
Published: June 2021

Purpose

In order to understand the status of the bridge reinforcement process, the construction process monitoring of the reinforced bridge is carried out. The T-beam bridge was tested using the truck loading test. The displacements and concrete strains of the bridge at mid-span were measured during the test.

Design/methodology/approach

This paper describes an innovative technique, external prestressing, used to strengthen a 36-year-old prestressed T-beam bridge. This paper introduces the construction process of the prestressed reinforcement method, and makes a theoretical analysis of the reinforced bridge through the establishment of the reinforcement model.

Findings

This study showed that the structural capacity and performance of the bridge were enhanced with externally prestressed steel strand strengthening.

Originality/value

The innovative reinforcement method of prestressed T-shaped bridge is put forward, which has guiding significance for similar bridge reinforcement and maintenance.