bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Delta Variant Remains Viable in Environmental Biofilms found in Meat Packaging Plants
Authors: Featherstone Austin B. , Mathijssen Arnold J. T. M. , Brown Amanda , Chitlapilly Dass Sapna
Published: June 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus that directly infects human airway epithelial cells and caused the COVID-19 pandemic. At the start of the pandemic in 2020, meat-packaging plants saw a surge in SARS-CoV-2 cases, which forced many to temporarily close. To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81 – 4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. In addition, we detected an increase in the biofilm biovolume in response to SARS-CoV-2 Delta variant which is also a concern for food safety due to the potential for foodborne pathogens to respond likewise when they come into contact with the virus. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants. With the highly infectious nature of some SARS-CoV-2 variants such as Delta, and more so with the Omicron variant, even a minimal amount of virus could have serious health implications for the spread and reoccurrence of SARS-CoV-2 outbreaks in meat packaging plants.
Comparative genomics of Japanese encephalitis virus shows low rates of recombination and a suite of sites under episodic diversifying selection
Authors: Sistrom Mark , Andrews Hannah , Edwards Danielle
Published: June 2023

Japanese encephalitis virus (JEV) is the dominant cause of viral encephalitis in the Asian region with 100,000 cases and 25,000 deaths reported annually. The genome is comprised of a single polyprotein that encodes three structural and seven non-structural proteins. We collated a dataset of 347 complete genomes from a number of public databases, and analysed the data for recombination, evolutionary selection and phylogenetic structure. There are low rates of recombination in JEV, subsequently recombination is not a major evolutionary force shaping JEV. We found a strong overall signal of purifying selection in the genome, which is the main force affecting the evolutionary dynamics in JEV. There are also a small number of genomic sites under episodic diversifying selection, especially in the envelope protein and non-structural proteins 3 and 5. Overall, these results support previous analyses of JEV evolutionary genomics and provide additional insight into the evolutionary processes shaping the distribution and adaptation of this important pathogenic arbovirus.

Author Summary

This comparative study of Japanese Encephalitis Virus is the largest genomic analysis of the virus to date. We undertake a suite of analyses to investigate phylogenetic relationships, rates of recombination and patterns of genomic selection. We show that recombination is not a significant driver of evolution in JEV, demonstrate support for previous phylogenetic reconstructions of the virus, and find a number of sites across the genome under episodic diversifying selection. These adaptive hotspots of evolution serve as key genomic points for the adaptive evolution of this important vector borne pathogen.
CC+: A Searchable Database of Validated Coiled coils in PDB Structures and AlphaFold2 Models
Authors: Kumar Prasun , Petrenas Rokas , Dawson William M. , Schweke Hugo , Levy Emmanuel D. , Woolfson Derek N.
Published: June 2023

α-Helical coiled coils are common tertiary and quaternary elements of protein structure. In coiled coils, two or more α helices wrapped around each other to form bundles. This apparently simple structural motif can generate many architectures and topologies. Understanding the variety of and limits on coiled-coil assemblies and their sequence-to-structure relationships impacts on protein structure, design, and engineering. Coiled coil-forming sequences can be predicted from heptad repeats of hydrophobic and polar residues,hpphppp, although this is not always reliable. Alternatively, coiled-coil structures can be identified using the program SOCKET, which finds knobs-into-holes (KIH) packing between side chains of neighboring helices. SOCKET also classifies coiled-coil architecture and topology, thus allowing sequence-to-structure relationships to be garnered. In 2009, we used SOCKET to create a relational database of coiled-coil structures, CC+, from the RCSB Protein Data Bank (PDB). Here we report an update of CC+following the recent explosion of structural data and the success of AlphaFold2 in predicting protein structures from genome sequences. With the most-stringent SOCKET parameters, CC+contains ≈12,000 coiled-coil assemblies from experimentally determined structures, and ≈120,000 potential coiled-coil structures within single-chain models predicted by AlphaFold2 across 48 proteomes. CC+allows these and other less-stringently defined coiled coils to be searched at various levels of structure, sequence, and side-chain interactions. The identified coiled coils can be viewed directly from CC+using the Socket2 application, and their associated data can be downloaded for further analyses. CC+is available freely athttp://coiledcoils.chm.bris.ac.uk/CCPlus/Home.html. It will be regularly updated automatically.

FOR THE BROADER AUDIENCE

Protein assemblies and protein-protein interactions are key to all biological processes. α-Helical coiled coils are one of the most common modes of directing and stabilising these interfaces. Here, we report an updated CC+database of structurally validated coiled coils from experimental protein structures and AlphaFold2 models. CC+contains many thousands of coiled-coil structures and models, associated parameters, and sequences. It enables the compilation of rich datasets for advancing protein structure, design, and engineering research.
FixNCut: Single-cell genomics through reversible tissue fixation and dissociation
Authors: Jiménez-Gracia Laura , Marchese Domenica , Nieto Juan C. , Caratù Ginevra , Melón-Ardanaz Elisa , Gudiño Victoria , Roth Sara , Wise Kellie , Ryan Natalie K , Jensen Kirk B. , Hernando-Momblona Xavier , Bernardes Joana P. , Tran Florian , Sievers Laura Katharina , Schreiber Stefan , van den Berge Maarten , Kole Tessa , van der Velde Petra L. , Nawijn Martijn C. , Rosenstiel Philip , Batlle Eduard , Butler Lisa M. , Parish Ian A. , Plummer Jasmine , Gut Ivo , Salas Azucena , Heyn Holger , Martelotto Luciano G.
Published: June 2023

The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs.
Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2
Authors: Goradia Nishit , Werner Stefan , Mullapudi Edukondalu , Greimeier Sarah , Merkens Lina , Lang Andras , Mertens Haydyn , Węglarz Aleksandra , Sander Simon , Chojnowski Grzegorz , Wikman Harriet , Ohlenschläger Oliver , von Amsberg Gunhild , Pantel Klaus , Wilmanns Matthias
Published: June 2023

While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions. The specific properties of these repeated interactions open up new therapeutic opportunities.
Bacterial tolerance to host-exuded specialized metabolites structures the maize root microbiome
Authors: Thoenen Lisa , Giroud Caitlin , Kreuzer Marco , Waelchli Jan , Gfeller Valentin , Deslandes-Hérold Gabriel , Mateo Pierre , Robert Christelle A.M. , Ahrens Christian H. , Rubio-Somoza Ignacio , Bruggmann Rémy , Erb Matthias , Schlaeppi Klaus
Published: June 2023

Plants exude specialized metabolites from their roots and these compounds are known to structure the root microbiome. However, the underlying mechanisms are poorly understood. We established a representative collection of maize root bacteria and tested their tolerance against benzoxazinoids, the dominant specialized and bioactive metabolites in the root exudates of maize plants.In vitroexperiments revealed that benzoxazinoids inhibited bacterial growth in a strain- and compound-dependent manner. Tolerance against these selective antimicrobial compounds depended on bacterial cell wall structure. Further, we found that native root bacteria isolated from maize tolerated the benzoxazinoids better compared to non-host Arabidopsis bacteria. This finding suggests the adaptation of the root bacteria to the specialized metabolites of their host plant. Bacterial tolerance to 6-methoxy-benzoxazolin-2-one (MBOA), the most abundant and selective antimicrobial metabolite in the maize rhizosphere, correlated significantly with the abundance of these bacteria on benzoxazinoid-exuding maize roots. Thus, strain-dependent tolerance to benzoxazinoids largely explained the abundance pattern of bacteria on maize roots. Abundant bacteria generally tolerated MBOA, while low abundant root microbiome members were sensitive to this compound. Our findings reveal that tolerance to plant specialized metabolites is an important competence determinant for root colonization. We propose that bacterial tolerance to plant-secreted antimicrobial compounds is an underlying mechanism determining the structure of host-specific microbial communities.

Significance Statement

Diverse microbial communities colonize plant roots. They feed on carbon rich root exudates which contain a diverse mix of chemicals including primary and specialized metabolites. Here we show that specialized metabolites act as selective antibiotics to shape the root bacterial communities. By growing single isolates of maize root bacteria in the presence of benzoxazinoidsin vitro, we find that the strains differ greatly in their tolerance to benzoxazinoids. Their different levels of tolerance largely explained their abundance on benzoxazinoid-exuding roots. Our work shows how plant specialized metabolites act to shape the maize root microbial community and thus deepened our mechanistic understanding of how plants shape their microbiome.
Warming affects routine swimming activity and novel odour molecular response in larval zebrafish
Authors: Sourisse Jade M. , Bonzi Lucrezia C. , Semmelhack Julie , Schunter Celia
Published: June 2023

Temperature is a primary factor affecting the survival, development, and physiology of aquatic ectothermic animals and global warming of water bodies may therefore impact several biological levels of aquatic life. Understanding the effects of near-future predicted temperature changes on the behaviour and the underlying molecular mechanisms of aquatic animals is of particular importance, since behaviour mediates key interactions and, in turn, population dynamics. In this study, we investigate the effects of elevated developmental temperature on locomotor behaviour and olfactory learning in the zebrafish,Danio rerio. We exposed zebrafish from cleavage embryonic stage to either current day control (28°C) or predicted future elevated temperature (30°C) for seven days. Overall, warming reduced the total routine swimming distance and caused the upregulation of a small number of genes involved in metabolism and neuron development, suggesting accelerated development at elevated temperature. When fish were exposed to two different olfactory cues, namely catfish cue, a non-alarming but novel odour, and injured conspecifics alarm cue expected to cause a fear reaction, warming differently affected larvae response to the two cues. In particular, a large transcriptional reprogramming was observed at elevated temperature in response to novel odour exposure, with upregulation of cell signalling, neuron development and neuron functioning genes. As this response was coupled with downregulation of genes involved in protein translation and ATP metabolism, it indicates that novel odour recognition in future-predicted thermal conditions will require energetic trade-offs between expensive baseline processes and responsive functions. To also evaluate their learning abilities at both temperatures, 7 days post fertilization (dpf) zebrafish were conditioned with a mixture of injured conspecifics alarm cue and non-alarming catfish cue. Regardless of temperature, no behavioural (freezing) nor gene expression changes were detected, reinforcing our previous findings that warming mainly affects zebrafish molecular response to novel odours. Overall, our results show that future thermal conditions will likely impact developing stages, causing energy trade-offs following olfactory detection of novel substances in the environment.
The role of GpsB in cell morphogenesis ofStaphylococcus aureus
Authors: Costa Sara F. , Saraiva Bruno M. , Veiga Helena , Marques Leonor B. , Schäper Simon , Sporniak Marta , Vega Daniel E. , Jorge Ana M. , Duarte Andreia M. , Brito António D. , Tavares Andreia C. , Reed Patricia , Pinho Mariana G.
Published: June 2023

For decades, cells of the gram-positive bacterial pathogenStaphylococcus aureuswere thought to lack a dedicated elongation machinery. However,S. aureuscells were recently shown to elongate before division, in a process that requires a SEDS (Shape Elongation Division and Sporulation) / PBP (Penicillin Binding Protein) pair for peptidoglycan synthesis, consisting of the glycosyltransferase RodA and the transpeptidase PBP3. In ovococci and rod-shaped bacteria the elongation machinery, known as elongasome, is composed of various proteins besides a dedicated SEDS/PBP pair. To identify proteins involved in the elongation ofS. aureus, we screened the Nebraska Transposon Mutant Library, which contains transposon mutants in virtually all non-essential staphylococcal genes, for mutants with modified cell shape. We confirmed the roles of RodA/PBP3 inS. aureuselongation and identified GpsB, SsaA, and RodZ as additional proteins involved in this process. ThegpsBmutant showed the strongest phenotype, mediated by the partial delocalization from the division septum of PBP2, the only bifunctional PBP inS. aureus, with both glycosyltransferase and transpeptidase activity, and of the PBP4 transpeptidase. Increased levels of these PBPs at the cell periphery result in higher levels of peptidoglycan insertion throughout the entire cell, overriding the RodA/PBP3-mediated peptidoglycan synthesis at the outer edge of the septum, which leads to cell elongation. As a consequence, in the absence of GpsB,S. aureuscells become more spherical.
Auditory cortex anatomy reflects multilingual phonological experience
Authors: Kepinska Olga , Dalboni da Rocha Josue , Tuerk Carola , Hervais-Adelman Alexis , Bouhali Florence , Green David W. , Price Cathy J. , Golestani Narly
Published: June 2023

This study explores the relationship between the anatomy of the auditory cortex and multilingual experience, shedding light on the complex mechanisms of auditory processing in humans. Integrating previous research on auditory information processing and the impact of bi- and multilingualism on brain structure, we investigate how the morphology of auditory brain regions reflects individuals’ language experience and, more specifically, their phonological repertoire. Leveraging two distinct samples comprising over 200 participants, each exposed to between 1 and 7 languages encompassing 36 different languages, we explore whether the morphological variability of auditory brain regions reflects individual language experience, specifically focusing on the phonological repertoire. Additionally, we examine the potential influence of typological distances between languages spoken by multilingual individuals on the neural signatures of multilingualism within the auditory cortex. Our findings revealed a relationship between the average thickness of the left and right second transverse temporal gyrus (TTG) and participants’ language experience. Model comparisons demonstrated that the inclusion of phoneme-level information in the language experience index accounted for the greatest variance in average TTG thickness (bilaterally). The direction of this effect was negative, indicating that a more extensive and more phonologically diverse language experience was associated with thinner cortices in the second TTG. Across two independent datasets, we provide robust evidence linking the degree of language experience and typological distance between languages to cortical thickness in early auditory brain regions. We propose that this phenomenon may reflect experience-driven pruning and neural efficiency, warranting further investigation through longitudinal studies of language acquisition. Moreover, our findings support the notion that experiences with typologically similar languages differ from those with typologically distant languages, offering valuable insights into the intricate relationship between language diversity and brain structure. Our findings also indicate that early auditory regions seem to represent phoneme-level cross-linguistic information, contrary to the most established models of language processing in the brain, which suggest that phonological processing happens in more lateral posterior STG and STS.
Topological constraints and finite-size effects in quantitative polymer models of chromatin organization
Authors: Abdulla Amith Z. , Tortora Maxime M. C. , Vaillant Cédric , Jost Daniel
Published: June 2023

Polymer physics simulations have provided a versatile framework to quantitatively explore the complex mechanisms driving chromosome organization. However, simulating whole chromosomes over biologically-relevant timescales at high resolution often constitutes a computationally-intensive task — while genes or other regions of biological interest may typically only span a small fraction of the full chromosome length. Conversely, only simulating the sub-chromosomal region of interest might provide an over-simplistic or even wrong description of the mechanism controlling the 3D organization. In this work, we characterize what should be the minimal length of chromosome to be simulated in order to correctly capture the properties of a given restricted region. In particular, since the physics of long, topologically-constrained polymers may significantly deviate from those of shorter chains, we theoretically investigate how chromosomes being a long polymer quantitatively affects the structure and dynamics of its sub-segments. We show that increasing the total polymer length impacts on the topological constraints acting on the system and thus affects the compaction and mobility of sub-chains. Depending on the entanglement properties of the system, we derive a phenomenological relation defining the minimal total length to account for to maintain a correct topological regime. We finally detail the implications of these conclusions in the case of several specific biological systems.

Abstract Figure
Inferring the direction of introgression using genomic sequence data
Authors: Thawornwattana Yuttapong , Huang Jun , Flouri Tomáš , Mallet James , Yang Ziheng
Published: June 2023

Genomic data are informative about the history of species divergence and interspecific gene flow, including the direction, timing, and strength of gene flow. However, gene flow in opposite directions generates similar patterns in multilocus sequence data, such as reduced sequence divergence between the hybridizing species. As a result, inference of the direction of gene flow is challenging. Here we investigate the information about the direction of gene flow present in genomic sequence data using likelihood-based methods under the multispecies-coalescent-with-introgression (MSci) model. We analyze the case of two species, and use simulation to examine cases with three or four species. We find that it is easier to infer gene flow from a small population to a large one than in the opposite direction, and easier to infer inflow (gene flow from outgroup species to an ingroup species) than outflow (gene flow from an ingroup species to an outgroup species). It is also easier to infer gene flow if there is a longer time of separate evolution between the initial divergence and subsequent introgression. When introgression is assumed to occur in the wrong direction, the time of introgression tends to be correctly estimated and the Bayesian test of gene flow is often significant, while estimates of introgression probability can be even greater than the true probability. We analyze genomic sequences fromHeliconiusbutterflies to demonstrate that typical genomic datasets are informative about the direction of interspecific gene flow, as well as its timing and strength.
Septin organization is regulated by the Gpa1 Ubiquitination Domain and Endocytic Machinery during the yeast pheromone response
Authors: Johnson Cory P. , Shrestha Sudati , Hart Andrew , Jarvis Katherine F. , Genrich Loren E. , Latario Sarah G. , Leclerc Nicholas , Systuk Tetiana , Scandura Matthew , Geohegan Remi P. , Khalil André , Kelley Joshua B.
Published: June 2023

The septin cytoskeleton plays a key role in the morphogenesis of the yeast mating projection, forming structures at the base of the projection. The yeast mating response uses the G-protein coupled receptor (GPCR), Ste2, to detect mating pheromone and initiate mating projection morphogenesis. Desensitization of the Gα, Gpa1, by the Regulator of G-protein Signaling (RGS), Sst2, is required for proper septin organization and morphogenesis. We hypothesized that Gpa1 would utilize known septin regulators to control septin organization. We found that single deletions of the septin chaperone Gic1, the Cdc42 GAP Bem3, and the endocytic adaptor proteins Ent1 and Ent2 rescued the polar cap accumulation of septins in the hyperactive Gα. We hypothesized that hyperactive Gα might increase the rate of endocytosis of a pheromone-responsive cargo, thereby altering where septins are localized. Mathematical modeling predicted that changes in endocytosis could explain the septin organizations we find in WT and mutant cells. Our results show that Gpa1-induced disorganization of septins requires clathrin-mediated endocytosis. Both the GPCR and the Gα are known to be internalized by clathrin-mediated endocytosis during the pheromone response. Deletion of the GPCR C-terminus to block internalization partially rescued septin organization. However, deleting the Gpa1 ubiquitination domain required for its endocytosis completely abrogated septin accumulation at the polarity site. Our data support a model where the location of endocytosis serves as a spatial mark for septin structure assembly and that desensitization of the Gα delays its endocytosis sufficiently that septins are placed peripheral to the site of Cdc42 polarity.
Proinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2
Authors: Cremer Tom , Hoelen Hanneke , van de Weijer Michael L. , Janssen George M , Costa Ana. I. , van Veelen Peter A. , Lebbink Robert Jan , Wiertz Emmanuel J.H.J.
Published: June 2023

Type 1 diabetes (T1D) is characterized by HLA class I-mediated presentation of autoantigens on the surface of pancreatic β-cells. Recognition of these autoantigens by CD8+T cells results in the destruction of pancreatic β-cells and, consequently, insulin deficiency. Most epitopes presented at the surface of β-cells derive from the insulin precursor molecule proinsulin. The intracellular processing pathway(s) involved in the generation of these peptides are poorly defined. In this study, we show that a proinsulin B-chain antigen (PPIB5-14) originates from proinsulin molecules that are processed by ER-associated protein degradation (ERAD) and thus originate from ER-resident proteins. Furthermore, screening genes encoding for E2 ubiquitin conjugating enzymes, we identified UBE2G2 to be involved in proinsulin degradation. These results indicate that insulin-derived peptides, presented by HLA-class I molecules at the cell surface, originate from ER-resident proinsulin that has been dislocated to the cytosol for subsequent degradation. These insights into the pathway involved in the generation of insulin-derived peptides emphasize the importance of proinsulin processing in the ER to T1D pathogenesis and identify novel targets for future therapies that may cure or even prevent T1D.

Graphical abstract
Differentially abundant bacteria drive the N2-fixation of a widespread moss in the forest-tundra transition zone
Authors: Escolástico-Ortiz Dennis Alejandro , Blasi Charlotte , Bellenger Jean-Philippe , Derome Nicolas , Villarreal-A Juan Carlos
Published: June 2023

Bryophytes maintain symbiosis with epiphytic bacteria influencing the local nutrient budget. Moss bacterial communities are composed of a core microbiome and bacteria recruited from environmental sources. Notably, symbiotic N2-fixing bacteria contribute to the N budget in northern ecosystems through biological nitrogen fixation. This process may be affected by the abundance of diazotrophs and moss nutrient content. We used the abundant mossRacomitrium lanuginosumin a forest tundra and shrub tundra in Northern Quebec, Canada, to investigate the bacterial and diazotrophic communities associated with habitat type using amplicon sequencing of the bacterial 16S rRNA andnifHgenes and test whether the moss core microbiome has recruitment from the soil bacteria community. ThenifHamplicons and element analysis were used to test the effect of diazotrophic abundance and moss nutrient content on N2-fixation activity estimated by acetylene reduction assays. Moss microbial communities between tundra types hosted similar bacterial diversity but differentially abundant groups. The core microbiome ofR. lanuginosumis composed of bacteria strongly associated with northern mosses with no significant recruitment from the soil. The relative abundances of dominant diazotrophs are significantly correlated with acetylene reduction rates. In contrast, the moss nutrient content did not significantly drive N2-fixation. The proteobacterial generaAzorhizobiumandRhodomicrobiumrepresent newly reported bacteria associated with N2-fixation rates in the tundra. We identified critical bacterial groups related to moss-bacterial symbiosis and N2-fixation in the forest-tundra transition zone, a changing environment susceptible to climate warming.
Efficient Sex Separation by Exploiting Differential Alternative Splicing of a Dominant Marker inAedes aegypti
Authors: Weng Shih-Che , Antoshechkin Igor , Marois Eric , Akbari Omar S.
Published: June 2023

Only female mosquitoes consume blood and transmit deadly human pathogens. Therefore, it is critical to remove females before conducting releases for genetic biocontrol interventions. Here we describe a robust sex-sorting approach termed SEPARATOR (SexingElementProduced byAlternativeRNA-splicing ofATransgenicObservableReporter) that exploits sex-specific alternative splicing of an innocuous reporter to ensure exclusive dominant male-specific expression. Using SEPARATOR, we demonstrate reliable sex selection from larval and pupal stages inAedes aegypti, and use a Complex Object Parametric Analyzer and Sorter (COPAS®) to demonstrate scalable high-throughput sex-selection of first instar larvae. Additionally, we use this approach to sequence the transcriptomes of early larval males and females and find several genes that are sex-specifically expressed in males. SEPARATOR can simplify mass production of males for release programs and is designed to be cross-species portable and should be instrumental for genetic biocontrol interventions.
RAMAN DEVELOPMENTAL MARKERS IN ROOT CELL WALLS ARE ASSOCIATED WITH LODGING TENDENCY IN TEF
Authors: Diehn Sabrina , Kirby Noa , Ben-Zeev Shiran , Alemu Muluken Demelie , Saranga Yehoshua , Elbaum Rivka
Published: June 2023

Tef (Eragrostis tef(Zucc.) Trotter) is an important staple crop in Ethiopia and Eritrea. Its grains are gluten-free and protein rich, so it is considered as a “super-food”. Adapting tef to modern farming practices could allow its intensive growth in other regions and enable larger communities to gain from its nutritional values. However, high lodging susceptibility prevents the application of mechanical harvest and causes significant yield losses. Lodging describes the displacement of roots (root lodging) or fracture of culms (stem lodging), forcing plants to bend or fall from their vertical position. Lodging is facilitated by various abiotic and biotic factors, and the lodging severity is increased in overpopulated fields. In this study, we aimed to understand the microstructural properties of crown roots, underlining tef tolerance/susceptibility to lodging. We analyzed plants at 5 and 10 weeks after emergence and compared trellised to lodged plants. Root cross sections from different tef genotypes were characterized by scanning electron microscopy, micro computed tomography and Raman micro spectroscopy. Lodging susceptible genotypes exhibited early tissue maturation, including developed aerenchyma, intensive lignification, and lignin with high levels of crosslinks. A comparison between trellised and lodged plants suggested that lodging itself does not affect the histology of root tissue. Furthermore, cell wall composition along plant maturation was typical to each of the tested genotypes independently of trellising. Our results suggest that it is possible to select lines that exhibit slow maturation of crown roots. Such lines are predicted to show reduction in lodging and facilitate mechanical harvest.
An Experimental Platform for Stochastic Analyses of Single Serotonergic Fibers in the Mouse Brain
Authors: Mays Kasie C. , Haiman Justin H. , Janušonis Skirmantas
Published: June 2023

The self-organization of the serotonergic matrix, a massive axon meshwork in all vertebrate brains, is driven by the structural and dynamical properties of its constitutive elements. Each of these elements, a single serotonergic axon (fiber), has a unique trajectory and can be supported by a soma that executes one of many available transcriptional programs. It necessitates the development of specialized methods for single-fiber analyses, both at the experimental and theoretical levels. We developed an integrated system that facilitates experimental isolation of single serotonergic fibers in brain tissue, including regions with high fiber densities, and demonstrated the potential of their quantitative analyses based on stochastic modeling. Single fibers were visualized using two transgenic mouse models, one of which is the first implementation of the Brainbow toolbox in this system. The trajectories of serotonergic fibers were automatically traced in the three spatial dimensions with a novel algorithm, and their properties were captured with a single parameter associated with the directional von Mises-Fisher probability distribution. The system represents an end-to-end workflow that can be imported into various studies, including those investigating serotonergic dysfunction in brain disorders. It also supports new research directions inspired by single-fiber analyses in the serotonergic matrix, including supercomputing simulations and modeling in physics.
Anthropogenic nest material use correlates with human landscape modifications in a global sample of birds
Authors: Sheard Catherine , Stott Lucy , Street Sally E. , Healy Susan D. , Sugasawa Shoko , Lala Kevin N.
Published: June 2023

As humans increasingly modify the natural world, many animals have responded by changing their behaviour. Predicting the extent of these responses is a key step in conserving these species. For example, the tendency for some species of birds to incorporate anthropogenic items – particularly plastic material – into their nests is of increasing concern, as in some cases this behaviour has harmful effects on both adults and young. Studies of this phenomenon, however, have to date been limited in geographic and taxonomic scope. To investigate the global correlates of anthropogenic (including plastic) nest material use, we used Bayesian phylogenetic mixed models and a dataset of recorded nest materials in 6,147 species of birds. We find that after controlling for research effort, anthropogenic nest material use is correlated with proximity to human landscape modification, synanthropic (artificial) nesting locations, breeding environment, and the number of materials that has been recorded within the species’ nest. We also demonstrate that anthropogenic nest material use is unrelated to body mass, range size, or conservation status. These results indicate that anthropogenic materials are more likely to be included in nests when they are more readily available, as well as potentially by species who have more flexibility in nest material choice.
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
Authors: Samelson Avi J. , Ariqat Nabeela , McKetney Justin , Rohanitazangi Gita , Parra Bravo Celeste , Bose Rudra , Travaglini Kyle J. , Lam Victor L. , Goodness Darrin , Dixon Gary , Marzette Emily , Jin Julianne , Tian Ruilin , Tse Eric , Abskharon Romany , Pan Henry , Carroll Emma C. , Lawrence Rosalie E. , Gestwicki Jason E. , Eisenberg David , Kanaan Nicholas M. , Southworth Daniel R. , Gross John D. , Gan Li , Swaney Danielle L. , Kampmann Martin
Published: June 2023

Aggregation of the protein tau defines tauopathies, which include Alzheimer’s disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation and subsequent dysfunction and death, but the underlying mechanisms are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi-based modifier screen in iPSC-derived neurons. The screen uncovered expected pathways, including autophagy, but also unexpected pathways, including UFMylation and GPI anchor synthesis. We discover that the E3 ubiquitin ligase CUL5SOCS4is a potent modifier of tau levels in human neurons, ubiquitinates tau, and is a correlated with vulnerability to tauopathies in mouse and human. Disruption of mitochondrial function promotes proteasomal misprocessing of tau, which generates tau proteolytic fragments like those in disease and changes tau aggregationin vitro. These results reveal new principles of tau proteostasis in human neurons and pinpoint potential therapeutic targets for tauopathies.
Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice
Authors: Norris Adriana C. , Yazlovitskaya Eugenia M. , Zhu Lin , Rose Bailey S. , May Jody C. , Gibson-Corley Katherine N. , McLean John A. , Stafford John M. , Graham Todd R.
Published: June 2023

Genetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. ATP10A translocates phosphatidylcholine and glucosylceramide across cell membranes, and these lipids or their metabolites play important roles in signal transduction pathways regulating metabolism. However, the influence of ATP10A on lipid metabolism in mice has not been explored. Here, we generated gene-specificAtp10Aknockout mice and show thatAtp10A-/-mice fed a high-fat diet did not gain excess weight relative to wild-type littermates. However,Atp10A-/-mice displayed female-specific dyslipidemia characterized by elevated plasma triglycerides, free fatty acids and cholesterol, as well as altered VLDL and HDL properties. We also observed increased circulating levels of several sphingolipid species along with reduced levels of eicosanoids and bile acids. TheAtp10A-/-mice also displayed hepatic insulin resistance without perturbations to whole-body glucose homeostasis. Thus, ATP10A has a sex-specific role in regulating plasma lipid composition and maintaining hepatic liver insulin sensitivity in mice.
Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission
Authors: Baltazar Murielle , Jacques Laura C. , Audshasai Teerawit , Yang Marie , Kadioglu Aras
Published: June 2023

Streptococcus pneumoniaeserotype 1 is a major cause of invasive pneumococcal disease. Despite its high attack rate, serotype 1 exhibits a low carriage prevalence within the population, which raises important questions about the relationship between carriage and transmission of hypervirulent pneumococcal strains between individuals. We compared the transmission dynamics of serotype 1 sequence type ST217 to serotype 2 strain D39 using a novel model of transmission in young adult mice. Donor index mice were intranasally infected with ST217, D39 or isogenic pneumolysin-deficient mutants and co-housed with recipient naive contact mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of shedding and nasal colonisation in index and contact mice. The role of the toxin pneumolysin in shedding, transmission and colonisation, and the host nasopharyngeal immune response were investigated. We show that ST217 was shed in index mice at significantly greater levels compared to D39. Upon viral co-infection, ST217 was shed and transmitted at a faster rate to contact mice and displayed higher transmission levels compared to D39. Interestingly, the toxin pneumolysin did not play a role in shedding. However, upon acquisition by contact mice, pneumolysin-dependent macrophage recruitment was observed in the nasopharynx. Our results show that the rapid and high transmission rate of serotype 1 is a key factor in its ability to disseminate quickly within the population and cause disease outbreaks.
Diversification of Nucleoside Analogues as Potent Antiviral Drug Leads
Authors: Scheeff Stephan , Wang Yan , Lyu Mao-Yun , Nasiri Ahmadabadi Behzad , Hau Sam Chun Kit , Hui Tony K. C. , Zhang Yufeng , Zuo Zhong , Chan Renee Wan Yi , Ng Billy Wai-Lung
Published: June 2023

Nucleoside analogues are potent antiviral agents, but the continuous emergence of pathogenic viruses demands novel and diverse structures. Herein, we have created a diversified library of highly bioactive and non-cytotoxic nucleoside analogues featuring an unprecedented carbobicyclic core that mimics natural ribonucleoside conformation. These regio- and stereo-divergent analogues exhibit up to 16-fold greater antiviral efficacy than the FDA-approved antiviral, ribavirin. Importantly, the carbobicyclic core structure is critical for the potent antiviral efficacy, thus opening up ample opportunities for further lead optimization and mechanistic investigations.

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Resilient performance on construction projects in the post-pandemic era: an organizational perspective
Authors: Tonetto Mirela Schramm , Formoso Carlos Torres , Saurin Tarcisio Abreu , Bonesi De Luca Fabiana , Lora Fernanda Pavan , Lantelme Elvira
Published: June 2023

Purpose

The COVID-19 pandemic offered a unique glimpse into the resilience of construction projects, shedding light on several learning opportunities. The purpose of this paper is to develop propositions for the improvement of resilient performance in construction in the post-pandemic era.

Design/methodology/approach

The propositions were developed based on an empirical study in Brazil. Data collection involved the analysis of regulations, interviews with health experts, managers, and workers, in addition to non-participant observations of the use of 37 control practices in 39 construction sites comparing the work-as-imagined and the work-as-done. The practices were classified in a hierarchy of controls.

Findings

Seven propositions for the improvement of resilient performance were developed, addressing collaboration between construction companies, slack resources, new health and safety practices, production planning and control, digital technologies, visual management, and organizational culture. These propositions emphasize organizational support for resilience. This is in contrast to the nature of most observed practices (57%) that relied on administrative controls and personal protective equipment, which are measures dependent on behaviors that resemble resilience at the individual level.

Originality/value

Although much has been studied on COVID-19 implications for construction projects, previous empirical studies have not adopted the organizational resilience perspective as the main theoretical background.
Discard the false and retain the true: the effect of hypocrisy on the cognitive legitimacy of social enterprises
Authors: Zhang Kun , Zhang Xiu-e , Xu Xuejiao
Published: June 2023

Purpose

Hypocrisy often observed in the social responsibility practices of commercial enterprises is more likely to occur in social enterprises. However, this issue has received little research attention. This study explores, from a consumer perspective, the formation of perceived hypocrisy and its impact on the cognitive legitimacy of social enterprises.

Design/methodology/approach

This research conducted two experiments, and data were collected from 515 subjects in China to test the proposed hypotheses.

Findings

Behavioral inconsistency in social enterprises leads to consumers' perceived hypocrisy. The higher the perceived hypocrisy towards social enterprises, the weaker their cognitive legitimacy of social enterprises. At a lower level of inconsistency, the perceived hypocrisy of social enterprises was lower than that of commercial enterprises. Egoistic attribution to prosocial behavior moderated the negative effect of perceived hypocrisy on cognitive legitimacy. The stronger the egoistic attribution, the greater is the negative effect of perceived hypocrisy on the cognitive legitimacy of social enterprises.

Practical implications

Social entrepreneurs should be acutely aware of the harmful effects of hypocrisy on social enterprises. Social enterprises should not exaggerate their propaganda or be consistent with their words and actions.

Originality/value

This study innovatively analyzes the damage to the cognitive legitimacy of social enterprises caused by the hypocrisy that tends to occur in commercial enterprises and argues from the consumer viewpoint. These findings enrich the perspective on exploring social enterprise legitimacy.
Artificial intelligence for supplier scouting: an information processing theory approach
Authors: Guida Michela , Caniato Federico , Moretto Antonella , Ronchi Stefano
Published: June 2023

Purpose

The objective of this paper is to study the role of artificial intelligence (AI) in supporting the supplier scouting process, considering the information and the capabilities required to do so.

Design/methodology/approach

Twelve cases of IT and information providers offering AI-based scouting solutions were studied. The unit of analysis was the AI-based scouting solution, specifically the relationship between the provider and the buyer. Information processing theory (IPT) was adopted to address information processing needs (IPNs) and capabilities (IPCs).

Findings

Among buyers, IPNs in supplier scouting are high. IT and information providers can meet the needs of buyers through IPCs enabled by AI-based solutions. In this way, the fit between needs and capabilities can be reached.

Originality/value

The investigation of the role of AI in supplier scouting is original. The application of IPT to study the impact of AI in business processes is also novel. This paper contributes by investigating a phenomenon that is still unexplored and unconsolidated in a business context.
Activity sampling in the construction industry: a review and research agenda
Authors: Lee Tsu Yian , Ahmad Faridahanim , Sarijari Mohd Adib
Published: June 2023

Purpose

Activity sampling is a technique to monitor onsite labourers' time utilisation, which can provide helpful information for the management level to implement suitable labour productivity improvement strategies continuously. However, there needs to be a review paper that compiles research on activity sampling studies to give readers a thorough grasp of the research trend. Hence, this paper aims to investigate the activity sampling techniques applied in earlier research from the angles of activity categories formation, data collection methods and data analysis.

Design/methodology/approach

The method used in this paper is a systematic review guided by the PRISMA framework. The search was conducted in Scopus and Web of Science. The inclusion and exclusion criteria were applied, selecting 70 articles published between 2011 and 2022 for data extraction and analysis. The analysis method involved a qualitative synthesis of the findings from the selected articles.

Findings

Activity sampling is broadly divided into four stages: targeting trade, determining activity categories, data collection and data analysis. This paper divides the activity categories into three levels and classifies the data collection methods into manual observation, sensor-based activity sampling and computer vision-based activity sampling. The previous studies applied activity sampling for two construction management purposes: labour productivity monitoring and ergonomic safety monitoring. This paper also further discusses the scientific research gaps and future research directions.

Originality/value

This review paper contributes to the body of knowledge in construction management by thoroughly understanding current state-of-the-art activity sampling techniques and research gaps.