bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive map of human glucokinase variant activity
Authors: Gersing Sarah , Cagiada Matteo , Gebbia Marinella , Gjesing Anette P. , Coté Atina G. , Seesankar Gireesh , Li Roujia , Tabet Daniel , Stein Amelie , Gloyn Anna L. , Hansen Torben , Roth Frederick P. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus
Published: May 2022

Glucokinase (GCK) regulates insulin secretion to maintain appropriate blood glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic hypoglycemia (HH) or hyperglycemia associated with GCK-maturity-onset diabetes of the young (GCK-MODY), collectively affecting up to 10 million people worldwide. Patients with GCK-MODY are frequently misdiagnosed and treated unnecessarily. Genetic testing can prevent this but is hampered by the challenge of interpreting novel missense variants. Here we exploited a multiplexed yeast complementation assay to measure both hyper- and hypoactive GCK variation, capturing 97% of all possible missense and nonsense variants. Activity scores correlated with in vitro catalytic efficiency, fasting glucose levels in carriers of GCK variants and with evolutionary conservation. Hypoactive variants were concentrated at buried positions, near the active site, and at a region of known importance for GCK conformational dynamics. Some hyperactive variants shifted the conformational equilibrium towards the active state through a relative destabilization of the inactive conformation. Our comprehensive assessment of GCK variant activity promises to facilitate variant interpretation and diagnosis, expand our mechanistic understanding of hyperactive variants, and inform development of therapeutics targeting GCK.
Impact of Salmonella genome rearrangement on gene expression
Authors: Waters Emma V. , Tucker Liam A. , Ahmed Jana K. , Wain John , Langridge Gemma C.
Published: May 2022

In addition to nucleotide variation, many bacteria also undergo changes at a much larger scale via rearrangement of their genome structure around long repeat sequences. These rearrangements result in genome fragments shifting position and/or orientation in the genome without necessarily affecting the underlying nucleotide sequence. To date, scalable techniques have not been applied to genome structure (GS) identification, so it remains unclear how extensive this variation is and the extent of its impact upon gene expression. However, the emergence of multiplexed, long-read sequencing overcomes the scale problem, as reads of several thousand bases are routinely produced that can span long repeat sequences to identify the flanking chromosomal DNA, allowing GS identification. Genome rearrangements were generated in Salmonella enterica serovar Typhi through long-term culture at ambient temperature. Colonies with rearrangements were identified via long-range PCR and subjected to long-read nanopore sequencing to confirm genome variation. Four rearrangements were investigated for differential gene expression using transcriptomics. All isolates with changes in genome arrangement relative to the parent strain were accompanied by changes in gene expression. Rearrangements with similar fragment movements demonstrated similar changes in gene expression. The most extreme rearrangement caused a large imbalance between the origin and terminus of replication and was associated with differential gene expression as a factor of distance moved towards or away from the origin of replication. Genome structure variation may provide a mechanism through which bacteria can quickly adapt to new environments and warrants routine assessment alongside traditional nucleotide level measures of variation.
Best practice recommendations for sample preservation in metabarcoding studies: a case study on diatom environmental samples
Authors: Ana Baricevic , Cécile Chardon , Maria Kahlert , Maaria Karjalainen Satu , Daniela Maric Pfannkuchen , Martin Pfannkuchen , Frédéric Rimet , Mirta Smodlaka Tankovic , Rosa Trobajo , Valentin Vasselon , Jonas Zimmermann , Agnès Bouchez
Published: May 2022

The development of DNA metabarcoding and High-Throughput Sequencing for diatoms is nowadays offering an interesting approach to assess their communities in freshwater and marine ecosystems. In the context of the implementation of these genomic methods to environmental monitoring, protocol constraints are moving from scientific to operational applications, requiring operational guidelines and standards. In particular, the first steps of the diatom metabarcoding process, which consist of sampling and storage, have been addressed in various ways in scientific and pilot studies.

The objective of this study was to compare three currently applied preservation protocols through different storage durations (ranging from one day to one year) for phytobenthos and phytoplankton samples intended for diatom DNA metabarcoding analysis. The experimental design included four freshwater and two marine samples from sites of diverse ecological characteristics. The impact of the preservation and storage was assessed through diatom metabarcoding endpoints: DNA quality and quantity, diversity and richness, community composition and ecological index values (for freshwater samples). The yield and quality of extracted DNA only decreased for freshwater phytobenthos samples preserved with ethanol. Diatom diversity was not affected and their taxonomic composition predominantly reflects the site origin. Only rare taxa (below 100 reads) differed among methods and durations. Thus, importance of preservation method choice is important for low-density species (rare, invasive, threatened or toxic species). However, for biomonitoring purposes, freshwater ecological index values were not affected whatever the preservation method and duration considered (including ethanol preservation), reflecting the site ecological status.

This study proved that diatom metabarcoding is robust enough to replace or complement the current approach based on morphotaxonomy, paving the way to new possibilities for biomonitoring. Thus, accompanied by operational standards, the method will be ready to be confidently deployed and prescribed in future regulatory monitoring.
A systematic approach to study protein-substrate specificity enables the identification of Ssh1 substrate range
Authors: Cohen Nir , Aviram Naama , Schuldiner Maya
Published: May 2022

Many cellular functions are carried out by protein pairs, or families, providing robustness alongside functional diversity. For such processes, it remains a challenge to map the degree of specificity versus promiscuity. Protein-protein interactions (PPIs) can be used to inform on these matters as they highlight cellular locals, regulation and, in cases where proteins affect other proteins – substrate range. However, methods to study transient PPIs systematically are underutilized. In this study we create a novel approach to study stable as well as transient PPIs in yeast. Our approach, Cel-lctiv (CELlular biotin-Ligation forCapturingTransientInteractionsinVivo), uses high- throughput pairwise proximity biotin ligation for uncovering PPIs systematically andin vivo. As a proof of concept we study the homologous translocation pores Sec61 and Ssh1. We show how Cel-lctiv can uncover the unique substrate range for each translocon allowing us to pinpoint a specificity determinator driving interaction preference. More generally this demonstrates how CEl-lctiv can provide direct information on substrate specificity even for highly homologous proteins.
Plasticity facilitates rapid evolution
Authors: Burtsev Mikhail , Anokhin Konstantin , Bateson Patrick
Published: May 2022

Developmental plasticity enables organisms to cope with new environmental challenges. If deploying such plasticity is costly in terms of time or energy, the same adaptive behavior could subsequently evolve through piecemeal genomic reorganisation that replaces the requirement to acquire that adaptation by individual plasticity. Here we report a new dimension to the way in which plasticity can drive evolutionary change leading to ever greater complexity in biological organization. Our model deploys the concept of partially overlapping functional systems. We found that plasticity accelerated dramatically the evolutionary accumulation of adaptive systems in model organisms with relatively low rates of mutation. The effect of plasticity on the evolutionary growth of complexity was even greater when the number of elements needed to construct a functional system was increased. These results suggest that as the difficulty of challenges from the environment become greater, so plasticity exerts an ever more powerful role in meeting those challenges and in opening up new avenues for the subsequent evolution of complex adaptations.
The H2A.Z.1/PWWP2A/NuRD-associated protein HMG20A controls early head and heart developmental transcription programs
Authors: Herchenröther Andreas , Gossen Stefanie , Friedrich Tobias , Reim Alexander , Daus Nadine , Diegmüller Felix , Leers Jörg , Sani Hakimeh Moghaddas , Gerstner Sarah , Schwarz Leah , Stellmacher Inga , Szymkowiak Laura Victoria , Nist Andrea , Stiewe Thorsten , Borggrefe Tilman , Mann Matthias , Mackay Joel P. , Bartkuhn Marek , Borchers Annette , Lan Jie , Hake Sandra B.
Published: May 2022

Abstract/Summary

Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes including NuRD, and show that it localizes to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects inXenopus laevis.Our data indicate that craniofacial malformations are caused by defects in neural crest cell (NCC) migration and cartilage formation. These developmental defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CMs). Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial- mesenchymal transition (EMT) and cardiac differentiation, thereby providing insights into the regulatory circuits controlled by HMG20A. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of the intricate developmental transcription programs that guide NCC and cardiomyocyte differentiation.
Adsorption of Pulmonary and Exogeneous Surfactants on SARS-CoV-2 Spike Protein
Authors: Santo Kolattukudy P. , Neimark Alexander V.
Published: May 2022

COVID-19 is transmitted by inhaling SARS-CoV-2 virions, which are enveloped by a lipid bilayer decorated by a “crown” of Spike protein protrusions. In the respiratory tract, virions interact with surfactant films composed of phospholipids and cholesterol that coat lung airways. Here, we explore by using coarse-grained molecular dynamics simulations the physico-chemical mechanisms of surfactant adsorption on Spike proteins. With examples of zwitterionic dipalmitoyl phosphatidyl choline, cholesterol, and anionic sodium dodecyl sulphate, we show that surfactants form micellar aggregates that selectively adhere to the specific regions of S1 domain of the Spike protein that are responsible for binding with ACE2 receptors and virus transmission into the cells. We find high cholesterol adsorption and preferential affinity of anionic surfactants to Arginine and Lysine residues within S1 receptor binding motif. These findings have important implications for informing the search for extraneous therapeutic surfactants for curing and preventing COVID-19 by SARS-CoV-2 and its variants.
Mapping the T cell repertoire to a complex gut bacterial community
Authors: Nagashima Kazuki , Zhao Aishan , Atabakhsh Katayoon , Weakley Allison , Jain Sunit , Meng Xiandong , Cheng Alice G. , Wang Min , Higginbottom Steven , Dimas Alex , Murugkar Pallavi , Fischbach Michael A.
Published: May 2022

Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response1–5. However, the specificity of microbiome-induced T cells has not been explored at the strain level across the gut community. Here, we colonize germ-free mice with a complex defined community (97 or 112 bacterial strains) and profile T cell responses to each strain individually. Unexpectedly, the pattern of T cell responses suggests that many T cells in the gut repertoire recognize multiple bacterial strains from the community. We constructed T cell hybridomas from 92 T cell receptor (TCR) clonotypes; by screening every strain in the community against each hybridoma, we find that nearly all of the bacteria-specific TCRs exhibit a one-to-many TCR-to-strain relationship, including 13 abundant TCR clonotypes that are polyspecific for 18 Firmicutes in the community. By screening three pooled bacterial genomic libraries against 13 pooled hybridomas, we discover that they share a single target: a conserved substrate-binding protein (SBP) from an ABC transport system. Treg and Th17 cells specific for an epitope from this protein are abundant in community-colonized and specific-pathogen-free mice. Our work reveals that T cell recognition of Firmicutes is focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.
Task prioritization modulates low frequency EEG dynamics reflecting proactive cognitive control
Authors: Liegel Nathalie , Schneider Daniel , Wascher Edmund , Arnau Stefan
Published: May 2022

Most neuroscientific studies investigating mental effort apply unspecific effort allocation paradigms. In contrast, the present EEG study targets specific effort allocation during task prioritization.

Twenty-eight participants performed a cued number classification task during the retention interval of a working memory task including retrospective cues. One of two possible number classifications was done per trial. Each trial started with a cue indicating which of the two tasks would be more important in the upcoming trial. Subjects were told to engage in both tasks, but to concentrate on the important one. Feedback given at the end of each trial was calculated based on task performance, with scores obtained from the relevant task being tripled.

Participants performed significantly better in either task when it was important compared to when not.Task prioritization modulates theta, alpha and beta oscillations, predominantly during task preparation. Multivariate pattern analysis revealed that the exact type of the two possible number classifications was decodable, however, decoding accuracy did not depend on task importance. Hemispheric alpha power asymmetries indicating attentional orienting between working memory representations also did not depend on task importance. The findings suggest that task prioritization primarily affects proactive cognitive control on a superordinate level.
Heading direction tracks internally directed selective attention in visual working memory
Authors: Thom Jude L. , Nobre Anna C. , van Ede Freek , Draschkow Dejan
Published: May 2022

We shift our gaze even when we orient attention internally to visual representations in working memory. Here, we show the bodily orienting response associated with internal selective attention is widespread as it also includes the head. In three virtual reality (VR) experiments, participants remembered two visual items. After a working memory delay, a central colour cue indicated which item needed to be reproduced from memory. After the cue, head movements became biased in the direction of the memorised location of the cued memory item – despite there being no items to orient towards in the external environment. The heading-direction bias had a distinct temporal profile from the gaze bias. Our findings reveal that directing attention within the spatial layout of visual working memory bears a strong relation to the overt head orienting response we engage when directing attention to sensory information in the external environment. The heading-direction bias further demonstrates common neural circuitry is engaged during external and internal orienting of attention.
Elemental content of a host-parasite relationship in the threespine stickleback
Authors: Braat Megan , Grunberg Rita L. , Bolnick Daniel I.
Published: May 2022

Parasite infections are ubiquitous and their effects on hosts may play a role in ecosystem processes. Ecological stoichiometry provides a framework to study linkages between consumers and ecosystem process, but the stoichiometric traits of host-parasite associations are rarely quantified. Specifically, whether parasites’ elemental ratios closely resemble those of their host or if infection is related to host stoichiometry remains less known. To answer such questions, we measured the elemental content (%C, %N, and %P) and ratios (C:N, C:P, and N:P) of parasitized and unparasitized Gasterosteus aculeatus (three-spined stickleback) and their cestode parasite, Schistocephalus solidus. Host and parasite elemental content were distinct from each other, and parasites were generally higher in %C and lower in %N and %P. Parasite infections were related to some elemental ratios, specifically C:N, with more intense parasite infections corresponding to hosts with lower C:N ratio. Parasite stoichiometry was independent of their host and there was no relationship between host and parasite stoichiometry. Instead, parasite body mass and parasite density were important drivers of parasite stoichiometry where larger parasites had lower %C, %N, and %P,. Overall, these potential effects of parasite infections on host stoichiometry along with parasites’ distinct elemental compositions suggest parasites may further contribute to how hosts store and cycle nutrients.
A potent and selective inhibitor for the modulation of MAGL activity in the neurovasculature
Authors: Kemble Alicia , Hornsperger Benoit , Ruf Iris , Richter Hans , Benz Jörg , Kuhn Bernd , Heer Dominik , Wittwer Matthias , Engelhardt Britta , Grether Uwe , Collin Ludovic
Published: May 2022

Chronic inflammation and blood–brain barrier dysfunction are key pathological hallmarks of neurological disorders such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Major drivers of these pathologies include pro-inflammatory stimuli such as prostaglandins, which are produced in the central nervous system by the oxidation of arachidonic acid in a reaction catalyzed by the cyclooxygenases COX1 and COX2. Monoacylglycerol lipase hydrolyzes the endocannabinoid signaling lipid 2-arachidonyl glycerol, enhancing local pools of arachidonic acid in the brain and leading to cyclooxygenase-mediated prostaglandin production and neuroinflammation. Monoacylglycerol lipase inhibitors were recently shown to act as effective anti-inflammatory modulators, increasing 2-arachidonyl glycerol levels while reducing levels of arachidonic acid and prostaglandins, including PGE2 and PGD2. In this study, we characterized a novel, highly selective, potent and reversible monoacylglycerol lipase inhibitor (MAGLi 432) in a mouse model of lipopolysaccharide-induced blood–brain barrier permeability and in both human and mouse cells of the neurovascular unit: brain microvascular endothelial cells, pericytes and astrocytes. We confirmed the expression of monoacylglycerol lipase in specific neurovascular unit cells in vitro, with pericytes showing the highest expression level and activity. However, MAGLi 432 did not ameliorate lipopolysaccharide-induced blood–brain barrier permeability in vivo or reduce the production of pro-inflammatory cytokines in the brain. Our data confirm monoacylglycerol lipase expression in mouse and human cells of the neurovascular unit and provide the basis for further cell-specific analysis of MAGLi 432 in the context of blood–brain barrier dysfunction caused by inflammatory insults.
The effect of dietary chitin on Atlantic salmon (Salmo salar) chitinase activity, gene expression, and microbial composition
Authors: Holen Matilde Mengkrog , Sandve Simen Rød , Harvey Thomas Nelson , Jin Yang , Angell Inga Leena , Rudi Knut , Kent Matthew Peter
Published: May 2022

Background

Chitin is a common component in the natural diet of many fish, and a range of chitinases with the potential to down chitin have been identified. Yet whether chitin is metabolized in fish is still unclear. Here we used a combination of chitinase activity assay, transcriptomics, and 16S rRNA bacterial analysis to assess the effect of chitin supplementation on Atlantic salmon gene expression and microbial community.

Results

Atlantic salmon express multiple genes associated with chitin metabolism, and we show that the expression and activity of Atlantic salmon chitinases are not affected by the addition of dietary chitin. We do, however, demonstrate an association between gut microbial composition, chitinase activity in the gut, and host chitinase expression.

Conclusion

The findings presented here support the idea that chitin metabolism genes are linked to the maintenance of a chitin-based barrier in the teleost gut. These results contribute to a greater understanding of chitin metabolism in fish.
Early patterning followed by tissue growth establishes proximo-distal identity in Drosophila Malpighian tubules
Authors: Beaven Robin , Denholm Barry
Published: May 2022

Specification and elaboration of proximo-distal (P-D) axes for structures or tissues within a body occurs secondarily from that of the main axes of the body. Our understanding of the mechanism(s) that pattern P-D axes is limited to a few examples such as vertebrate and invertebrate limbs. Drosophila Malpighian/renal tubules (MipTs) are simple epithelial tubules, with a defined P-D axis. How this axis is patterned is not known, and provides an ideal context to understand patterning mechanisms of a secondary axis. Furthermore, epithelial tubules are widespread, and their patterning is not well understood. Here, we describe the mechanism that establishes distal tubule and show this is a radically different mechanism to that patterning the proximal MpT. The distal domain is patterned in two steps: distal identity is specified in a small group of cells at the earliest stage of MpT development through Wingless/Wnt signalling. Subsequently, this population is expanded by proliferation to generate the distal MpT domain. This mechanism enables distal identity to be established in the tubule in a domain of cells much wider than the effective range of Wingless.

Summary statement

How does proximo-distal patterning occur in the epithelial Malpighian/renal tubules? Cells are patterned early by a mechanism involving Wingless/Wnt, and expand by cell proliferation to generate a distal domain.
Developmental Morphogens Direct Human Induced Pluripotent Stem Cells Towards an Annulus Fibrosus-Like Cell Phenotype
Authors: Peredo Ana P. , Tsinman Tonia K. , Bonnevie Edward D. , Jiang Xi , Smith Harvey E. , Gullbrand Sarah E. , Dyment Nathaniel A. , Mauck Robert L.
Published: May 2022

Therapeutic interventions for intervertebral disc herniation remain scarce due to the inability of endogenous annulus fibrosus (AF) cells to respond to injury and drive tissue regeneration. Unlike other orthopaedic tissues, such as cartilage, delivery of exogenous cells to the site of annular injury remains underdeveloped, largely due to a lack of an ideal cell source and the invasive nature of cell isolation. Human induced pluripotent stem cells (iPSCs) can be differentiated to specific cell fates using biochemical factors and are, therefore, an invaluable tool for cell therapy approaches. While differentiation protocols have been developed for cartilage and fibrous connective tissues (e.g., tendon), the signals that regulate the induction and differentiation of human iPSCs towards the annulus fibrosus fate remain unknown. Here, we screened a number of candidate factors (and their combinations) and assessed the transcriptomic signatures of key signaling factors involved in embryonic AF development and differentiated function. The transcriptional signatures of treated cells were compared to those of mature human AF cells, and conditions that promoted expression of annulus fibrosus extracellular matrix genes and key transcription factors involved in embryonic AF development were identified. These findings represent an initial approach to guide human induced pluripotent stem cells towards an annulus fibrosus-like fate for cellular delivery strategies.
Mechanism of the cadherin-catenin F-actin catch bond interaction
Authors: Wang Amy , Dunn Alexander R. , Weis William I.
Published: May 2022

Mechanotransduction at cell-cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At cell-cell junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense and transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, is weak in solution but is strengthened by applied force due to force-dependent transitions between weak and strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that the catch bond property principally resides in the αE-catenin actin-binding domain (ABD). Consistent with our previously proposed model, deletion of the first helix of the five-helix ABD bundle enables stable interactions with F-actin under minimal load that are well-described by a single-state slip bond, even when αE-catenin is complexed with β-catenin and E-cadherin. Our data argue for a conserved catch bond mechanism for adhesion proteins with structurally similar ABDs. We also demonstrate that a stably bound ABD strengthens load-dependent binding interactions between a neighboring complex and F-actin, but the presence of the other αE-catenin domains weakens this effect. These results provide mechanistic insight to the cooperative binding of the cadherin-catenin complex to F-actin, which regulate dynamic cytoskeletal linkages in epithelial tissues.
Expansion of information in scientific research papers
Authors: Abdullaeva Malika , Bromfield John J. , Sheldon I. Martin
Published: May 2022

Presenting information in papers allows readers to see the evidence for the research claims. The amount of information presented to readers is increasing in high impact factor scientific journals. The aim of the present study was to determine whether there was a similar expansion in the amount of information presented to readers in subject-specific journals. We examined 878 research papers that were published in the journals Biology of Reproduction and Reproduction during the first six months of 1989, 1999, 2009, and 2019. Although there were few differences between the journals, we found that between 1989 and 2019 the number of figures increased 1.5-fold, the number of figure panels increased 3.6-fold, and the number of display items increased 5.6-fold. Amongst the display items, the number of images per paper increased 10-fold, and the number of graphs per paper increased 3.7-fold. The median paper in 1989 was 8 pages long, contained 6 tables and/or figures, with 1 image and 4 graphs. In 2019 the median paper was 12 pages long, contained 7 tables and/or figures, with 13 images and 15 graphs. This expansion of information in subject-specific journals implies that authors, reviewers, and editors need to help readers digest complex biological messages without causing information overload.

Lay summary

We are living in an age of science and information. The amount of information presented in research papers has increased over time in the top science journals. Our research examined whether there has been a similar expansion in information in two influential subject-specific journals. We counted how much information was presented in 878 research papers across a 30-year period in the journals Biology of Reproduction and Reproduction. There were few differences between the two journals. But there was a striking increase in the information presented to readers in 2019 compared with 1989. The typical paper in 1989 was 8 pages long and contained 1 picture and 4 graphs. In 2019 the typical paper was 12 pages long and contained 13 pictures and 15 graphs. This expansion of information means that subject-specific journals must balance the presentation of complex biological messages with the risk of causing information overload.
A curated data resource of 214K metagenomes for characterization of the global resistome
Authors: Martiny Hannah-Marie , Munk Patrick , Brinch Christian , Aarestrup Frank M. , Petersen Thomas N.
Published: May 2022

The growing threat of antimicrobial resistance (AMR) calls for new epidemiological surveillance methods, as well as a deeper understanding of how antimicrobial resistance genes (ARGs) have transmitted around the world. The large pool of sequencing data available in public repositories provides an excellent resource for monitoring the temporal and spatial dissemination of AMR in different ecological settings. However, only a limited number of research groups globally have the computational resources allowing analyses of such data. We retrieved 442 Tbp of sequencing reads from 214,095 metagenomic samples from the European Nucleotide Archive (ENA) and aligned them using a uniform approach against ARGs and 16S/18S rRNA genes. Here, we present the results of this extensive computational analysis and share the counts of reads aligned. Over 6.76 · 108read fragments were assigned to ARGs and 3.21 · 109to rRNA genes, where we observed distinct differences in both the abundance of ARGs and the link between microbiome and resistome compositions across various sampling types. This collection is another step towards establishing a global surveillance of AMR and can serve as a resource for further research into the environmental spread and dynamic changes of ARGs.
Protrusion growth driven by myosin-generated force
Authors: Fitz Gillian N. , Weck Meredith L. , Bodnya Caroline , Perkins Olivia L. , Tyska Matthew J.
Published: May 2022

Actin-based protrusions are found on the surface of all eukaryotic cells, where they support diverse biological activities essential for life. Models of protrusion growth hypothesize that actin filament assembly provides the mechanical force for bending the plasma membrane outward. However, membrane-associated myosin motors are also abundant in protrusions, though their potential for contributing growth-promoting force remains unexplored. Using a novel inducible system that docks myosin motor domains to membrane binding modules with temporal control, we found that the application of myosin-generated force to the plasma membrane is sufficient for driving robust elongation of protrusions. Protrusion growth scaled with motor accumulation, required active, barbed end-directed force, and was independent of cargo delivery or the recruitment of canonical barbed end elongation factors. Application of growth-promoting force was also supported by structurally distinct myosin motor domains and membrane binding modules. We conclude that myosin-generated force can drive protrusion growth and this mechanism is likely active in diverse biological contexts.
Early embryonic mutations reveal dynamics of somatic and germ cell lineages in mice
Authors: Uchimura Arikuni , Matsumoto Hirotaka , Satoh Yasunari , Minakuchi Yohei , Wakayama Sayaka , Wakayama Teruhiko , Higuchi Mayumi , Hashimoto Masakazu , Fukumura Ryutaro , Toyoda Atsushi , Gondo Yoichi , Yagi Takeshi
Published: May 2022

De novo mutations accumulate with zygotic cell divisions. However, the occurrence of these mutations and the way they are inherited by somatic cells and germ cells remain unclear. Here, we present a novel method to reconstruct cell lineages. We identified mosaic mutations in mice using deep whole-genome sequencing and reconstructed embryonic cell lineages based on the variant allele frequencies of the mutations. The reconstructed trees were confirmed using nuclear transfer experiments and the genotyping of approximately 50 offspring of each tree. The most detailed tree had 32 terminal nodes and showed cell divisions from the fertilized egg to germ cell– and somatic cell–specific lineages, indicating at least five independent cell lineages that would be selected as founders of the primordial germ cells. The contributions of each lineage to germ cells and offspring varied widely. At the emergence of the germ cell–specific lineages, 10–15 embryonic mutations had accumulated, suggesting that the pregastrulation mutation rate is 1.0 mutation per mitosis. Subsequent mutation rates were 0.7 for germ cells and 13.2 for tail fibroblasts. Our results show a new framework to assess embryonic lineages; further, we suggest an evolutionary strategy for preserving heterogeneity owing to postzygotic mutations in offspring.
Towards kilohertz synchrotron coherent diffractive imaging
Authors: Hinsley Gerard N. , Kewish Cameron M. , van Riessen Grant A.
Published: May 2022

X-ray coherent diffractive imaging (CDI) techniques have been applied with widespread impact to study nanoscale material properties. New fast framing detectors may reveal dynamics that occur at millisecond timescales. This work demonstrates by simulation that kilohertz synchrotron CDI is possible, by making use of redundant information from static parts of the image field. Reconstruction ambiguities are strongly suppressed by applying a spatiotemporal constraint, obviating the need for slower methods of introducing diversity such as ptychography. The relationship between image fidelity and time resolution is investigated and shows that dynamics an order of magnitude faster can be reconstructed, compared with conventional CDI.
The structure and molecular dynamics of prolyl oligopeptidase from Microbulbifer arenaceous provide insights into catalytic and regulatory mechanisms
Authors: Huang Ping , Lv Ang , Yan Qiaojuan , Jiang Zhengqiang , Yang Shaoqing
Published: May 2022

Prolyl oligopeptidases (POPs) are atypical serine proteases that are unique in their involvement in the maturation and degradation of prolyl-containing peptide hormones and neuropeptides. They are potential pharmaceutical targets for the treatment of several neurodegenerative disorders, such as Alzheimer's disease. In this study, the catalytic and substrate-regulatory mechanisms of a novel bacterial POP from Microbulbifer arenaceous (MaPOP) were investigated. The crystal structure revealed that the catalytic triad of MaPOP was covered by the central tunnel of an unusual β-propeller domain. The tunnel not only provided the sole access to the active site for oligopeptides, but also protected large structured peptides or proteins from accidental proteolysis. The enzyme was able to cleave angiotensin I specifically at the carboxyl side of the internal proline residue, but could not hydrolyze long-chain bovine insulin B in vitro. Like the ligand-free structure, MaPOP bound to the transition-state analog inhibitor ZPR was also in a closed state, which was not modulated by the common `latching loop' found in other POPs. The substrate-assisted catalytic mechanism of MaPOP reported here may represent a common mechanism for all POPs. These results may facilitate a better understanding of the catalytic behavior of POPs under physiological conditions.
Realizing the promise of big data: how Taiwan can help the world reduce medical errors and advance precision medicine
Authors: Wang Kevin , Muennig Peter Alexander
Published: May 2022

Purpose

The study explores how Taiwan’s electronic health data systems can be used to build algorithms that reduce or eliminate medical errors and to advance precision medicine.

Design/methodology/approach

This study is a narrative review of the literature.

Findings

The body of medical knowledge has grown far too large for human clinicians to parse. In theory, electronic health records could augment clinical decision-making with electronic clinical decision support systems (CDSSs). However, computer scientists and clinicians have made remarkably little progress in building CDSSs, because health data tend to be siloed across many different systems that are not interoperable and cannot be linked using common identifiers. As a result, medicine in the USA is often practiced inconsistently with poor adherence to the best preventive and clinical practices. Poor information technology infrastructure contributes to medical errors and waste, resulting in suboptimal care and tens of thousands of premature deaths every year. Taiwan’s national health system, in contrast, is underpinned by a coordinated system of electronic data systems but remains underutilized. In this paper, the authors present a theoretical path toward developing artificial intelligence (AI)-driven CDSS systems using Taiwan’s National Health Insurance Research Database. Such a system could in theory not only optimize care and prevent clinical errors but also empower patients to track their progress in achieving their personal health goals.

Originality/value

While research teams have previously built AI systems with limited applications, this study provides a framework for building global AI-based CDSS systems using one of the world’s few unified electronic health data systems.
Poppy Gustafsson: redefining cybersecurity through AI
Authors: Qumer Syeda Maseeha , Ikrama Syeda
Published: May 2022

Study level/applicability

This case is meant for MBA students as a part of their leadership/information technology and system curriculum. It is suitable for classes in both offline and online mode.

Subject area

Human resources management/information technology and systems.

Case overview

The case discusses how Poppy Gustafsson (Gustafsson) (she), Cofounder and Chief Executive Officer of Darktrace plc, one of the world’s largest cyber-AI companies, is reinventing enterprise security by using artificial intelligence (AI) to detect and respond to cyberthreats to businesses and protect the public. Darktrace’s technology leverages the principles of the human immune system to autonomously defend organizations from cyberattacks, insider threats and AI warfare. In addition to leading a cutting-edge cybersecurity company, Gustafsson evangelizes gender diversity at Darktrace where 40% of employees and four C-level executives are women, a number nearly unheard of in the tech sector.The case chronicles the journey of Gustafsson and how she led the company to growth and success. Under her leadership, Darktrace has grown into a market leader in the AI cybersecurity space serving 5,600 customers in 100 countries, as of June 2021. Gustafsson not only redefined the cybersecurity space but also inspired women to pursue a career in the field of cybersecurity. She also collaborated with a social enterprise called WISE to encourage more girls to consider STEM careers.However, along the way, she faced several challenges including growing competition, procuring funds from investors, cybersecurity talent shortage and training personnel. Going forward, some of the challenges before Gustafsson would be to meet the changing cyber protection demands of customers; hire, train and retain highly skilled cybersecurity personnel; beat the competition in a saturated cybersecurity services space; sustain revenue growth; and post profits as Darktrace had incurred losses every year since its inception.

Expected learning outcomes

This case is designed to enable students to: understand the issues and challenges women face in the field of cybersecurity; understand the qualities required for a woman leader to lead a technology firm; study the leadership and management style of Gustafsson; understand the importance of transformational leadership in management; understand the role of Gustafsson in Darktrace’s growth and success; analyze the traits that Gustafsson possesses as a tech leader in an emerging cybersecurity space; understand the importance of gender diversity in cybersecurity; and analyze the challenges faced by Gustafsson going forward and explore ways in which she can overcome them.

Subject code

CSS: 11 Strategy.
Sustainable governance and climate-change disclosure in European banking: the role of the corporate social responsibility committee
Authors: Cosma Simona , Principale Salvatore , Venturelli Andrea
Published: May 2022

Purpose

The purposes of this paper are: firstly, to assess the disclosure related to climate change (CC) by major European banks to understand if the banks have grasped the most substantive aspects of the Task Force on Climate-related Financial Disclosures (TCFD) recommendations and secondly, to evaluate the contribution of a non-traditional committee (i.e. corporate social responsibility (CSR) committee) to TCFD-compliant disclosure.

Design/methodology/approach

Using content analysis and ordinary least squares regressions on a sample of 101 European banks, this study sought to investigate completeness, tone and forward-looking orientation of CC disclosure and explore the relationships between CSR committee and previous disclosure aspects.

Findings

This study shows that European banks have been able to reach an intermediate level of adequacy of compliance in terms of completeness of information but forward-looking orientation seems to be the aspect that needs the most improvement. The existence of a CSR committee dedicated to sustainability issues seems to constitute the difference between the banks in terms of disclosure. The results highlight vulnerabilities in disclosure and board characteristics relevant for improving CC disclosure.

Practical implications

Firms interested in strengthening stakeholder engagement and capturing strategic opportunities involved in CC should be encouraged to establish a CSR committee and appoint female directors in financial companies. This paper should be of interest to policymakers, governance bodies and boards of directors considering the initiative of corporate sustainable governance complementary to Directive 2014/95/EU on non-financial reporting by the European Commission.

Originality/value

To the best of the authors’ knowledge, no prior study has investigated the relationship between the CSR committee and the application of the TCFD’s recommendations in the European banking industry.
Orchestrating an experiential value proposition: the case of a Scandinavian automotive manufacturer
Authors: Eklund Andreas Aldogan , Berndt Adele , Sandberg Susanne
Published: May 2022

Purpose

This paper aims to advance the theoretical knowledge of how manufacturers develop a multisensory value proposition.

Design/methodology/approach

An exploratory case study with a global automotive manufacturer was conducted. Personal in-depth interviews with key informants within a manufacturer were performed to obtain in-depth knowledge and insights on how the manufacturer plans and designs a value proposition.

Findings

This paper reveals how a value proposition is created from a sensory marketing perspective, which includes orchestrating the sensory experience, harmonising sensory cues to ensure they provide a consistent experience, thereby providing a memorable experience.

Practical implications

Understanding how to offer value might assist managers in tailoring a unique experiential value proposition to position the brand.

Originality/value

This paper proposes a theoretical framework, enriching the understanding of the underlying mechanisms used to create an experiential value proposition. The framework illustrates that harmonising sensory cues based on brand-related stimuli fosters a memorable experience, which enables consumers to (sub)consciously infer value.
Impact of COVID-19 pandemic on the quantity surveying practices in Malaysia
Authors: Tan Shi Yen , Zainon Nurshuhada
Published: May 2022

Purpose

Malaysia has experienced a significant surge in COVID-19. The “new normal” has plunged construction players into one of the most challenging times in their history, including the quantity surveyors (QS). Playing a primary role from pre-construction to post-construction stages, QS is essential to ensure project success. This study aims to clarify the impact of COVID-19 on quantity surveying practices to provide a better understanding of the construction sector's downturn during the pandemic.

Design/methodology/approach

Preliminary exploratory interviews were conducted with ten QS, architects, project managers and engineers to identify quantity surveying practices affected by the pandemic, followed by a survey involving 222 respondents to determine the significance of these impacts.

Findings

It was found that quantity surveying practices involving site visits, such as variation work valuation and interim payment valuation, were the most affected by the pandemic. On the other hand, consultative services such as value management and advisory services were the least affected.

Research limitations/implications

The study faced data sampling limitations. Further research requires more insights on different groups of QS, such as consultants, contractors and developers, and reasons behind the difference in consensus between QS and non-QS respondents.

Practical implications

The insights from this research may help authorities and construction companies make necessary adjustments to ensure the quantity surveying profession remains resilient, hence a better chance of project success during a pandemic. This discovery can also be considered a significant opportunity to present the need for further development.

Originality/value

The findings are expected to explain how COVID-19 had affected the duties of QS and identify which impact is the most significant. This research will complement the existing publications on the impacts of COVID-19 on the construction industry.
Dissecting the effect of family business exposure on entrepreneurial implementation intention
Authors: Onjewu Adah-Kole Emmanuel , Haddoud Mohamed Yacine , Tony-Okeke Uchenna , Cao Dongmei , Nowiński Witold
Published: May 2022

Purpose

Scholars have typically examined family business exposure as an aggregate variable. However, it is probable that this trend oversimplifies the complexity of family exposure and its nuanced influence on entrepreneurial behaviour. Thus, to extend the theoretical boundary, this inquiry investigates distinct dimensions of family exposure in Nigeria while drawing on the theory of planned behaviour.

Design/methodology/approach

Data were collected from five public universities in Nigeria. A sample of 1,314 respondents was analysed using a partial least squares structural equation modelling approach to determine the influence of alternate family business exposures.

Findings

The results show that entrepreneurial exposure in the forms of parent, family member and work involvement have salient and distinctive influences on implementation intention to the extent that entrepreneurial self-efficacy, attitudes and subjective norms are uniquely impacted.

Originality/value

This study offers novel insights on the predictors of entrepreneurial implementation intention through the distinctive effects of (1) family member exposure, (2) parent exposure and (3) work involvement exposure among students in the family firm context.
Resiliency and meaningfulness in work: a job crafting perspective
Authors: Morales-Solis Juan Carlos , Chen Jiatian (JT) , May Douglas R. , Schwoerer Catherine E.
Published: May 2022

Purpose

The purpose of this paper is to study the role of task, relational and cognitive job crafting on the relationship between resiliency and meaningfulness in work.

Design/methodology/approach

This study used path analysis under the framework of structural equation modeling to test the hypotheses using a sample of 374 law enforcement employees.

Findings

Results from the analysis revealed a direct effect of resiliency on meaningfulness. This study also found that relational and cognitive crafting partially mediate these relationships.

Practical implications

Understanding the proactive strategies resilient employees can use to build meaning in work will help managers develop better training programs. The findings emphasize the importance of building social relations and positive reframing of work as a mechanism to bounce back from adverse circumstances.

Originality/value

This paper provides empirical evidence of the proactive actions resilient employees implement to build meaningfulness in work.