bluuebunny/crossref_metadata_2025 huggingface dataset:
AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration
Authors: Thotamune Waruna , Ubeysinghe Sithurandi , Rajarathna Chathuri , Kankanamge Dinesh , Olupothage Koshala , Chandu Aditya , Copits Bryan A. , Karunarathne Ajith
Published: June 2024

G protein-coupled receptors (GPCRs) are efficient Guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G protein heterotrimers in response to various extracellular stimuli, including neurotransmitters and light. GPCRs primarily broadcast signals through activated G proteins, GαGTP, and free Gβγ and are major disease drivers. Evidence shows that the ambient low threshold signaling required for cells is likely supplemented by signaling regulators such as non-GPCR GEFs and Guanine nucleotide Dissociation Inhibitors (GDIs). Activators of G protein Signaling 3 (AGS3) are recognized as a GDI involved in multiple health and disease-related processes. Nevertheless, understanding of AGS3 is limited, and no significant information is available on its structure-function relationship or signaling regulation in living cells. Here, we employedin silicostructure-guided engineering of a novel optogenetic GDI, based on the AGS3’s G protein regulatory (GPR) motif, to understand its GDI activity and induce standalone Gβγ signaling in living cells on optical command. Our results demonstrate that plasma membrane recruitment of OptoGDI efficiently releases Gβγ, and its subcellular targeting generated localized PIP3 and triggered macrophage migration. Therefore, we propose OptoGDI as a powerful tool for optically dissecting GDI-mediated signaling pathways and triggering GPCR-independent Gβγ signaling in cells andin vivo.
Baikal: Unpaired Denoising of Fluorescence Microscopy Images using Diffusion Models
Authors: Chaudhary Shivesh , Sankarapandian Sivaramakrishnan , Sooknah Matt , Pai Joy , McCue Caroline , Chen Zhenghao , Xu Jun
Published: June 2024

Fluorescence microscopy is an indispensable tool for biological discovery but image quality is constrained by desired spatial and temporal resolution, sample sensitivity, and other factors. Computational denoising methods can bypass imaging constraints and improve signal-tonoise ratio in images. However, current state of the art methods are commonly trained in a supervised manner, requiring paired noisy and clean images, limiting their application across diverse datasets. An alternative class of denoising models can be trained in a self-supervised manner, assuming independent noise across samples but are unable to generalize from available unpaired clean images. A method that can be trained without paired data and can use information from available unpaired highquality images would address both weaknesses. Here, we present Baikal, a first attempt to formulate such a framework using Denoising Diffusion Probabilistic Models (DDPM) for fluorescence microscopy images. We first train a DDPM backbone in an unconditional manner to learn generative priors over complex morphologies in microscopy images. We then apply various conditioning strategies to sample from the trained model and propose an optimal strategy to denoise the desired image. Extensive quantitative comparisons demonstrate better performance of Baikal over state of the art self-supervised methods across multiple datasets. We highlight the advantage of generative priors learnt by DDPMs in denoising complexFlywingmorphologies where other methods fail. Overall, our DDPM based denoising framework presents a new class of denoising methods for fluorescence microscopy datasets that achieve good performance without collection of paired high-quality images. Github repo:https://github.com/scelesticsiva/denoising/tree/main
Niche cytoskeletal architecture is required for proper stem cell signaling and oriented division in theDrosophilatestis
Authors: Vida Gabriela S. , Botto Elizabeth , DiNardo Stephen
Published: June 2024

Stem cells are critical to repair and regenerate tissues, and often reside in a niche that controls their behavior. TheDrosophilatestis niche has been a paradigm for niche-stem cell interactions and is used here to address the cell biological features that maintain niche structure and function during its steady-state operation. We report enrichment of the Myosin II (MyoII) and a key regulator of acto-myosin contractility (AMC), Rho Kinase (ROK), within the niche cell cortex at the interface with germline stem cells (GSCs). Compromising MyoII and ROK disrupts niche architecture, suggesting that AMC in niche cells is important to maintain the reproducible structure of this niche. Furthermore, defects in niche architecture cause changes in stem cell function. Our data suggest that the niche signals less robustly to adjacent germ cells, yet the disrupted structure permits increased numbers of cells to respond to the signal. Finally, compromising Myo II in niche cells leads to an increase in mis-oriented centrosomes in GSCs as well as defects in the centrosome orientation checkpoint. Ultimately, this work identifies a critical role for AMC-dependent maintenance of niche structure to ensure a proper complement of stem cells with correct execution of stem cell divisions.

Summary statement

Actomyosin contractility regulated niche architecture is critical for proper signaling and oriented division of germline stem cells.
Biases in routine influenza surveillance indicators used to monitor infection incidence and recommendations for improvement
Authors: Eales Oliver , McCaw James M. , Shearer Freya M.
Published: June 2024

Background

Monitoring how the incidence of influenza infections changes over time is important for quantifying the transmission dynamics and clinical severity of influenza. Infection incidence is difficult to measure directly, and hence other quantities which are more amenable to surveillance are used to monitor trends in infection levels, with the implicit assumption that they correlate with infection incidence.

Method

Here we demonstrate, through mathematical reasoning, the relationship between the incidence of influenza infections and three commonly reported surveillance indicators: 1) the rate per unit time of influenza-like illness reported through sentinel healthcare sites, 2) the rate per unit time of laboratory-confirmed influenza infections, and 3) the proportion of laboratory tests positive for influenza (‘test-positive proportion’).

Results

Our analysis suggests that none of these ubiquitously reported surveillance indicators are a reliable tool for monitoring influenza incidence. In particular, we highlight how these surveillance indicators can be heavily biased by: the dynamics of circulating pathogens (other than influenza) with similar symptom profiles; changes in testing rates; and differences in infection rates, symptom rates, and healthcare-seeking behaviour between age-groups and through time. We make six practical recommendations to improve the monitoring of influenza infection incidence. The implementation of our recommendations would enable the construction of more interpretable surveillance indicator(s) for influenza from which underlying patterns of infection incidence could be readily monitored.

Conclusion

The implementation of all (or a subset) of our recommendations would greatly improve understanding of the transmission dynamics, infection burden, and clinical severity of influenza, improving our ability to respond effectively to seasonal epidemics and future pandemics.
Structure ofGeobacillus stearothermophilusCas9: insights into the catalytic process and thermostability of CRISPR-Cas9
Authors: Shen Panpan , Zhang Lilan , Liu Beibei , Li Xian , Min Jian , Huang Jian-Wen , Chen Chun-Chi , Guo Rey-Ting
Published: June 2024

CRISPR-Cas9 has been developed as a powerful gene editing tool, but the mechanism governing the intricate catalytic process remains incompletely resolved. Here, the cryo-electron microscopy structures of thermostable Cas9 fromGeobacillus stearothermophilus(GeoCas9) in complex with sgRNA and target DNA are reported. The structure of GeoCas9 in complex with sgRNA reveals a slit termed L1-crevice comprising HNH, RuvC, and L1 helix as a transient storage site of 5’ spacer of sgRNA. When 5’ spacer is extracted to pair with the target DNA, L1-crevice collapses to trigger the subsequent HNH domain translocation. In addition, structural and biochemical analyses suggest that the resilience of GeoCas9 at elevated temperature is related to the unique PI domain conformation. These results advance our understanding into the catalytic process of Cas9 and unveil the molecular mechanism that accounts for the superior thermal profile of GeoCas9.
Intact protein barcoding enables one-shot identification of CRISPRi strains and their metabolic state
Authors: Pahl Vanessa , Lubrano Paul , Petras Daniel , Link Hannes
Published: June 2024

Simultaneous measurements of library barcodes and metabolites can facilitate the screening of metabolically engineered bacterial libraries. Here, we introduce a scalable method for the parallel measurement of protein-based library barcodes and metabolites using flow-injection mass spectrometry (FI-MS). Protein barcodes are based on ubiquitin, a small 76-amino-acid protein, which we labeled with N-terminal tags of six amino acids to identify bacterial strains. We demonstrate that FI-MS effectively detects intact ubiquitin proteins and identifies the N-terminal barcodes. In the same analysis, we semi-quantify relative concentrations of primary metabolites. As a proof of concept, we engineered six ubiquitin-barcoded CRISPRi strains targeting metabolic enzymes, and analyzed their metabolic profiles and ubiquitin barcodes using FI-MS. Our results show distinct metabolome changes within metabolic pathways targeted by CRISPRi. This method enables fast and simultaneously detection of library barcodes and intracellular metabolites, opening up new possibilities to measure metabolomes of engineered bacteria at scale.
Human placental organoids as a model to probe early gestation maternal immune dynamics
Authors: Slaby Emily M , Brown Elise , Becker Matthew W , Hansen Nathaniel , Sharma Ritin , Pirrotte Patrick , Weaver Jessica D
Published: June 2024

During pregnancy, the human placenta establishes tolerance toward fetal allogeneic tissue, where specialized trophoblast subtypes play a complex role in local and peripheral immunomodulation. However, due to inadequate models to study the early gestation of the human placenta, each trophoblast subtype's role in modulating the maternal immune response has remained elusive. Here, we derived human placental organoids from early gestation trophoblast stem cells to (1) identify patterns of immunomodulatory protein expression by trophoblast subtype and (2) evaluate the effects of the placental organoid secretome on immune cell activation and regulation. We show that the three primary trophoblast phenotypes had distinct influences on immune cell phenotype and activation and that three-dimensional culture significantly alters trophoblast immunomodulation relative to traditional two-dimensional trophoblast culture.
The GABAA receptor RDL modulates the auditory sensitivity of malaria mosquitoes.
Authors: Ellis David Andrew , Alampounti Alexandros , Suppermpool Anya , Georgiades Marcos , Freeman Elizabeth , Bagi Judit , Tytheridge Scott , Terrazas-Duque Daniela , Albert Joerg T , Andres Marta
Published: June 2024

Malaria mosquitoes mate in crowded, and noisy, swarms. A vital stage of their precopulatory behaviour involves detecting the faint flight tone of a mating partner amidst the noise from hundreds of other mosquitoes. This exquisite sensory performance is enabled by a complex auditory system with remarkable features. One such feature is their vast efferent control system, which provides the mosquito ear with the required plasticity to adapt to various external and internal changes. In this paper, we study the auditory role of GABA, one of the main efferent signalling molecules in the mosquito ear, and its interactions with octopamine, another neurotransmitter of the efferent network. We show that GABA is released in the malaria mosquito auditory nerve and that GABA receptors are expressed in the ear, including the GABAA receptor Resistance to Dieldrin (RDL), a target for the evolution of insecticide resistance. Using picrotoxin to antagonize RDL receptors, we discovered multiple auditory effects of GABA at the mechanical and electrical level. At the mechanical level, blocking RDL promotes the erection of antennal fibrillae and the cessation of flagellar self-sustained oscillations. These effects are not observed in knockouts of the octopamine receptor AgOctbeta2, suggesting that RDL auditory mechanical effects are mediated through octopamine release in the mosquito ear. Electrically, picrotoxin injection increases the spontaneous firing of auditory neurons and direct current (DC) responses of the nerve to mechanical stimulation both in wildtype and AgOctbeta2 mutants, indicating that RDL may also modulate auditory sensitivity via octopamine-independent pathways. In summary, our experiments uncover distinct auditory roles of GABA, as well as synergistic roles with octopamine. The data show a fundamental role of RDL in controlling the auditory function of malaria mosquitoes and implicate RDL signalling in mating of natural malaria mosquito populations.
Engineering a SARS-CoV-2 vaccine targeting the RBD cryptic-face via immunofocusing
Authors: Bruun Theodora U. J. , Do Jonathan , Weidenbacher Payton A.-B. , Kim Peter S.
Published: June 2024

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target of neutralizing antibodies. Although they are infrequently elicited during infection or vaccination, antibodies that bind to the conformation-specific cryptic face of the RBD display remarkable breadth of binding and neutralization across Sarbecoviruses. Here, we employed the immunofocusing technique PMD (protect, modify, deprotect) to create RBD immunogens (PMD-RBD) specifically designed to focus the antibody response towards the cryptic-face epitope recognized by the broadly neutralizing antibody S2X259. Immunization with PMD-RBD antigens induced robust binding titers and broad neutralizing activity against homologous and heterologous Sarbecovirus strains. A serum-depletion assay provided direct evidence that PMD successfully skewed the polyclonal antibody response towards the cryptic face of the RBD. Our work demonstrates the ability of PMD to overcome immunodominance and refocus humoral immunity, with implications for the development of broader and more resilient vaccines against current and emerging viruses with pandemic potential.
A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization
Authors: Cao Xiaofu , Huang Shiying , Wagner Mateusz M. , Cho Yuan-Ting , Chiu Din-Chi , Wartchow Krista M. , Lazarian Artur , McIntire Laura Beth , Smolka Marcus B. , Baskin Jeremy M.
Published: June 2024

Tools for acute manipulation of protein localization enable elucidation of spatiotemporally defined functions, but their reliance on exogenous triggers can interfere with cell physiology. This limitation is particularly apparent for studying mitosis, whose highly choreographed events are sensitive to perturbations. Here we exploit the serendipitous discovery of a phosphorylation-controlled, cell cycle-dependent localization change of the adaptor protein PLEKHA5 to develop a system for mitosis-specific protein recruitment to the plasma membrane that requires no exogenous stimulus. Mitosis-enabled Anchor-away/Recruiter System (MARS) comprises an engineered, 15-kDa module derived from PLEKHA5 capable of recruiting functional protein cargoes to the plasma membrane during mitosis, either through direct fusion or via GFP–GFP nanobody interaction. Applications of MARS include both knock sideways to rapidly extract proteins from their native localizations during mitosis and conditional recruitment of lipid-metabolizing enzymes for mitosis-selective editing of plasma membrane lipid content, without the need for exogenous triggers or perturbative synchronization methods.
Contractile fibroblasts are recruited to the growing mammary epithelium to support branching morphogenesis
Authors: Sumbal Jakub , Journot Robin P. , Faraldo Marisa M. , Koledova Zuzana Sumbalova , Fre Silvia
Published: June 2024

Fibroblasts are stromal cells found in connective tissue that are critical for organ development, homeostasis, and disease. Single-cell transcriptomic analyses have revealed a high level of inter- and intra-organ heterogeneity of fibroblasts. However, the functional implications and lineage relations of different fibroblast subtypes remain unexplored, especially in the mammary gland. Here we provide a comprehensive characterization of pubertal mammary fibroblasts, achieved using single-cell RNA sequencing, spatial mapping, and in vivo lineage tracing. Notably, we discovered a transient niche-forming population of specialized contractile fibroblasts that exclusively localize around the tips of the growing mammary epithelium and are recruited from the surrounding fat pad. Using functional organoid-fibroblast co-cultures we reveal that different fibroblast populations can acquire contractile features when in direct contact with the epithelium, promoting morphogenesis. In summary, our exhaustive characterization of these specialized cells provides new insights into mammary fibroblast heterogeneity and implicates their functional relevance for branching morphogenesis and lineage hierarchy during mouse mammary gland development.
Spectrin condensates provide a nidus for assembling the periodic axonal structure
Authors: Boyer Nicholas P. , Sharma Rohan , Wiesner Theresa , Delamare Antoine , Pelletier Florence , Leterrier Christophe , Roy Subhojit
Published: June 2024

Coordinated assembly of individual components into higher-order structures is a defining theme in biology, but underlying principles are not well-understood. In neurons, α/β spectrins, adducin, and actinfilaments assemble into a lattice wrapping underneath the axonal plasma membrane, but mechanistic events leading to this periodic axonal structure (PAS) are unclear. Visualizing PAS components in axons as they develop, we found focal patches in distal axons containing spectrins and adducin (but sparse actin filaments) with biophysical properties reminiscent of biomolecular condensation. Overexpressing spectrin-repeats – constituents of α/β-spectrins – in heterologous cells triggered condensate formation, and preventing association of βII-spectrin with actin-filaments/membranes also facilitated condensation. Finally, overexpressing condensate-triggering spectrin repeats in neurons before PAS establishment disrupted the lattice, presumably by competing with innate assembly, supporting a functional role for biomolecular condensation. We propose a condensation-assembly model where PAS components form focal phase-separated condensates that eventually unfurl into a stable lattice-structure by associating with subplasmalemmal actin. By providing local ‘depots’ of assembly parts, biomolecular condensation may play a wider role in the construction of intricate cytoskeletal structures.
EARLY NEUTROPHIL ACTIVATION AND NETs RELEASE IN THE PRISTANE-INDUCED LUPUS MICE MODEL
Authors: Carrasco Solange , Liphaus Bernadete L. , Peixoto Tatiana Vasconcelos , Lima Thais Martins , Ariga Sueli Kunimi Kubo , Jesus Queiroz Zelita Aparecida , de Matos Lobo Thays , Catanozi Sergio , Rodrigues Letícia Gomes , Filho Antônio Santos , Teodoro Walcy Rosolia , Velosa Ana Paula Pereira , Levy Débora , Soriano Francisco Garcia , Goldenstein-Schainberg Cláudia
Published: June 2024

Background

NETosis is recognized as an important source of autoantigens. Therefore, we hypothesized whether the pristane-induced lupus mice model shows early activation of neutrophils, the presence of low-density granulocytes (LDGs), and neutrophil extracellular traps (NETs) release, which could contribute to the development of a lupus phenotype.

Methods

Twelve female wild-type Balb/c mice were intraperitoneally injected with pristane (n=6; pristane group) or saline (n=6; control group). Five days after the injection, blood, peritoneal lavage, bone marrow, and spleen samples were collected for flow cytometry analyses of activated neutrophils (Ly6G+CD11b+), LDGs (CD15+CD14low), and NETs release (Sytox Green+).

Results

The pristane-induced mice group had a significantly increased number of blood activated neutrophils and LDGs as well as NETs released by these cells compared to the saline-injected control group and the basal values determined 12 days before the injection. The pristane group also had a significantly increased number of activated neutrophils, LDGs, and NETs released compared to the control group for the peritoneal lavage, bone marrow, and spleen.

Conclusions

We demonstrated early changes in the innate immune response such as an increased number of activated neutrophils and LDGs and mainly increased NETosis in the pristane-induced mice model which may be considered as the primary event triggering lupus development.
Dispensable genome and segmental duplications drive the genome plasticity inFusarium solani
Authors: Navasca Abbeah , Singh Jatinder , Rivera-Varas Viviana , Gill Upinder , Secor Gary , Baldwin Thomas
Published: June 2024

Fusarium solaniis a species complex encompassing a large phylogenetic clade with diverse members occupying varied habitats. We recently reported a unique opportunisticF. solaniassociated with unusual dark galls in sugarbeet. We assembled the chromosome-level genome of theF. solanisugarbeet isolate strain SB1 using Oxford Nanopore and Hi-C sequencing. SB1 has a large genome (59.38 Mb) organized into 15 chromosomes. The genome expansion is due to the high repeats and massive segmental duplications within its three potentially accessory chromosomes. These chromosomes are absent in the closest reference genome with chromosome-level assembly,F. vanettenii77-13-4. The extensive segmental duplications between the two SB1 chromosomes suggest that this isolate may have doubled its accessory genes. Further comparison of theF. solanistrain SB1 genome demonstrates inversions and syntenic regions to an accessory chromosome ofF. vanettenii77-13-4. The pan-genome of 12 publicly availableF. solaniisolates nearly reached gene saturation, with few new genes discovered after the addition of the last genome. Based on orthogroups and average nucleotide identity,F. solaniis not grouped by lifestyle or origin. The pan-genome analysis further revealed the enrichment of several enzymes-coding genes within the dispensable (accessory + unique genes) genome, such as hydrolases, transferases, oxidoreductases, lyases, ligases, isomerase, and dehydrogenase. The evidence presented here suggests that genome plasticity, genetic diversity, and adaptive traits inFusarium solaniare driven by the dispensable genome with significant contributions from segmental duplications.
UNC-6/Netrin promotes both adhesion and directed growth within a single axon
Authors: Nichols Ev L. , Lee Joo , Shen Kang
Published: June 2024

During development axons undergo long-distance migrations as instructed by guidance molecules and their receptors, such as UNC-6/Netrin and UNC-40/DCC. Guidance cues act through long-range diffusive gradients (chemotaxis) or local adhesion (haptotaxis). However, how these discrete modes of action guide axonsin vivois poorly understood. Using time-lapse imaging of axon guidance inC. elegans, we demonstrate that UNC-6 and UNC-40 are required for local adhesion to an intermediate target and subsequent directional growth. Exogenous membrane-tethered UNC-6 is sufficient to mediate adhesion but not directional growth, demonstrating the separability of haptotaxis and chemotaxis. This conclusion is further supported by the endogenous UNC-6 distribution along the axon’s route. The intermediate and final targets are enriched in UNC-6 and separated by a ventrodorsal UNC-6 gradient. Continuous growth through the gradient requires UNC-40, which recruits UNC-6 to the growth cone tip. Overall, these data suggest that UNC-6 stimulates stepwise haptotaxis and chemotaxisin vivo.
Implementing a clinical pathway for diagnosing and treating acute HIV infection among key populations attending sexual health clinics in Indonesia: cohort profile of the INTERACT study
Authors: Irwanto  , Kawi Nurhayati H. , Luis Hendry , Sihotang Erik P. , Januraga Pande Putu , Oktaviani Margareta , Suwarti  , Rahmawati Dwi P. , Sukmaningrum Evi , Yanihastuti Evy , Dijkstra Maartje , Sanders Eduard J. , Wignall F. Stephen , Gedela Keerti , Hamers Raph L. ,   INTERACT Study Group
Published: June 2024

Background

To reduce the high HIV incidence among key populations in Indonesia, we implemented a clinical pathway for screening, diagnosis and treatment of acute HIV infection (AHI) in sexual health clinics in Jakarta and Bali. This paper presents a cohort profile and analysis of baseline data on the study uptake, diagnostic yield, and estimated AHI prevalence and screening cascade outcomes.

Methods

We performed a baseline analysis of 1879 individuals who underwent AHI screening at three sexual health clinics in Jakarta and Bali between May and December 2023, comprising a risk-score assessment, fourth-generation antibody/p24 antigen-based rapid diagnostic test (RDT; Abbott Determine HIV Early Detect) and HIV-PCR (Xpert) testing.

Results

Median age was 27 years (IQR24-31), and 75.4% were male. Men who have sex with men (MSM) accounted for 50.4%, clients of sex workers 20.1%, and sex workers 5.2%. Of 1866 participants tested at study enrolment, 113 (6.1% [113/1866]) had chronic HIV (antibody-positive) and 6 (0.34% [6/1748]) had AEHI. HIV-PCR testing led to a 5.3% (95%CI1.9-11.2) increase in confirmed HIV diagnoses. The number needed to test to detect one AEHI case was 291 (1748/6) overall and 169 (842/5) among MSM. Overall HIV and AHI prevalence was 6.4% (95%CI 5.3-7.6; 119/1866) and 0.34% (95%CI0.12-0.74; 6/1748) overall; and 10.8% (95%CI8.9-13.0; 102/940) and 0.53% (95%CI 0.17-1.2; 5/940) among MSM. The Abbott Determine HIV Early Detect RDT only detected 2 (18.2%) of 11 AEHI cases. 113 (95.0%) newly diagnosed individuals were linked to care and started ART, of whom 75 (66.4%) on the same day and 104 (92.0%) within a week (median 0 days, range 0-93).

Conclusion

AHI screening, diagnosis and prompt treatment is feasible among high-risk urban MSM in Indonesia. Further evaluations are needed to estimate clinical impact and cost-effectiveness of AHI screening in this setting. The study continues accrual and follow-up, and provides a platform for future immuno-virological, social science, and intervention studies in Indonesia.
Combinatorial Design Testing in Genomes with POLAR-seq
Authors: Ciurkot Klaudia , Lu Xinyu , Malyshava Anastasiya , Soro Livia , Lees Aidan , Gorochowski Thomas E. , Ellis Tom
Published: June 2024

Synthetic biology projects increasingly use modular DNA assembly or synthetic in vivo recombination to generate diverse combinatorial libraries of genetic constructs for testing. But as these designs expand to multigene systems it becomes challenging to sequence these in a cost-effective way that reveals the genotype to phenotype relationships in the libraries. Here, we introduce a new quick, low-cost method designed for assessing combinational designs of genome-integrated multigene constructs that we callPoolofLongAmplifiedReads (POLAR) sequencing. POLAR-seq takes genomic DNA isolated from library pools and uses long range PCR to amplify target genomic regions up to 35 kb long containing combinatorial designs. The pool of long amplicons is then directly read by nanopore sequencing with full length reads then used to identify the gene content and structural variation of individual genotypes in the library and read count indicating how abundant a genotype is within the pool. Using yeast cells with loxP-containing synthetic gene clusters that rearrange in vivo in the presence of Cre recombinase, we demonstrate how POLAR-seq can be used to identify global patterns from combinatorial experiments, find the most abundant genotypes in a pool and also be adapted to sequence-verify gene clusters from isolated strains.
Right-handed neutrino as a common progenitor of baryon number asymmetry and dark matter
Authors: Suematsu Daijiro
Published: June 2024

Cosmological and astrophysical observations suggest that both energy densities of baryon and dark matter take the same order values in the present Universe. We propose a scenario to give an answer for this problem in a scotogenic model and its extension. The model naturally provides dark matter candidates as its crucial ingredients to explain the small neutrino mass. If a neutral component of an inert doublet scalar plays a role of dark matter and leptogenesis occurs at TeV scales, both dark matter abundance and baryon number asymmetry could be explained with a same mother particle. Coincidence between the order of their energy densities might be understood through such a background.

Published by the American Physical Society
2024
Primordial Black Holes with QCD Color Charge
Authors: Alonso-Monsalve Elba , Kaiser David I.
Published: June 2024

We describe a realistic mechanism whereby black holes with significant QCD color charge could have formed during the early Universe. Primordial black holes (PBHs) could make up a significant fraction of the dark matter if they formed well before the QCD confinement transition. Such PBHs would form by absorbing unconfined quarks and gluons and hence could acquire a net color charge. We estimate the number of PBHs per Hubble volume with near-extremal color charge for various scenarios and discuss possible phenomenological implications.

Published by the American Physical Society
2024
Spatial distribution of local elastic moduli in nanocrystalline metals
Authors: Krief Menahem , Ashkenazy Yinon
Published: June 2024

Elastoplastic properties of nanocrystalline metals are nonuniform on the scale of the grain size, and this nonuniformity affects macroscopic quantities as, in these systems, a significant part of the material is at or adjacent to a grain boundary. We use molecular dynamics simulations to study the spatial distributions of local elastic moduli in nanograined pure metals and analyze their dependence on grain size. Calculations are performed for copper and tantalum with grain sizes ranging from 5 to 20 nm. Shear-modulus distributions for grain and grain-boundary atoms were calculated. It is shown that the noncrystalline grain boundary has a wide shear-modulus distribution, which is grain-size independent, while grains have a peaked distribution, which becomes sharper with increasing grain size. Average elastic moduli of the bulk, grains, and grain boundary are calculated as a function of grain size. The atomistic simulations show that the reduction of total elastic moduli with decreasing grain size is mainly due to a resulting larger grain-boundary atoms fraction, and that the total elastic moduli can be approximated by a simple weighted average of larger grain elastic moduli and a lower grain-boundary elastic moduli.

Published by the American Physical Society
2024
Soft X-ray wavefront sensing at an ellipsoidal mirror shell
Authors: Braig Christoph , Probst Jürgen , Löchel Heike , Pina Ladislav , Krist Thomas , Seifert Christian
Published: June 2024

A reliable `in situ' method for wavefront sensing in the soft X-ray domain is reported, developed for the characterization of rotationally symmetric optical elements, like an ellipsoidal mirror shell. In a laboratory setup, the mirror sample is irradiated by an electron-excited (4.4 keV), micrometre-sized (∼2 µm) fluorescence source (carbonKα, 277 eV). Substantially, the three-dimensional intensity distributionI(r) is recorded by a CCD camera (2048 × 512 pixels of 13.5 µm) at two positions along the optical axis, symmetrically displaced by ±21–25% from the focus. The transport-of-intensity equation is interpreted in a geometrical sense from plane to plane and implemented as a ray tracing code, to retrieve the phase Φ(r) from the radial intensity gradient on a sub-pixel scale. For reasons of statistical reliability, five intra-/extra-focal CCD image pairs are evaluated and averaged to an annular two-dimensional map of the wavefront error {\cal W}. In units of the test wavelength (C Kα), an r.m.s. value \sigma_{\cal{W}} = ±10.9λ0and a peak-to-valley amplitude of ±31.3λ0are obtained. By means of the wavefront, the focus is first reconstructed with a result for its diameter of 38.4 µm, close to the direct experimental observation of 39.4 µm (FWHM). Secondly, figure and slope errors of the ellipsoid are characterized with an average of ±1.14 µm and ±8.8 arcsec (r.m.s.), respectively, the latter in reasonable agreement with the measured focal intensity distribution. The findings enable, amongst others, the precise alignment of axisymmetric X-ray mirrors or the design of a wavefront corrector for high-resolution X-ray science.
Roentgenoscopy of laser-induced projectile impact testing
Authors: Wang Xue , Yao Chunxia , Zhang Bingbing , Zhang Dongsheng , Shi Caijuan , Tao Ye , Sun Darui
Published: June 2024

Laser-induced projectile impact testing (LIPIT) based on synchrotron imaging is proposed and validated. This emerging high-velocity, high-strain microscale dynamic loading technique offers a unique perspective on the strain and energy dissipation behavior of materials subjected to high-speed microscale single-particle impacts. When combined with synchrotron radiation imaging techniques, LIPIT allows for in situ observation of particle infiltration. Two validation experiments were carried out, demonstrating the potential of LIPIT in the roentgenoscopy of the dynamic properties of various materials. With a spatial resolution of 10 µm and a temporal resolution of 33.4 µs, the system was successfully realized at the Beijing Synchrotron Radiation Facility 3W1 beamline. This innovative approach opens up new avenues for studying the dynamic properties of materials in situ.
Clinical characteristics of adolescents and emerging adults presenting for integrated posttraumatic stress and substance use treatment
Authors: Peach Natalie , Kihas Ivana , Isik Ashling , Cassar Joanne , Barrett Emma Louise , Cobham Vanessa , Back Sudie E. , Perrin Sean , Bendall Sarah , Brady Kathleen , Ross Joanne , Teesson Maree , Bezzina Louise , Dobinson Katherine A. , Schollar-Root Olivia , Milne Bronwyn , Mills Katherine L.
Published: June 2024

Purpose

Adolescence and emerging adulthood are key developmental stages with high risk for trauma exposure and the development of mental and substance-use disorders (SUDs). This study aims to compare the clinical profiles of adolescents (aged 12–17 years) and emerging adults (aged 18–25 years) presenting for treatment of posttraumatic stress disorder (PTSD) and SUD.

Design/methodology/approach

Data was collected from the baseline assessment of individuals (n = 55) taking part in a randomized controlled trial examining the efficacy of an integrated psychological therapy for co-occurring PTSD and SUDs (PTSD+SUD) in young people.

Findings

Both age groups demonstrated complex and severe clinical profiles, including high-frequency trauma exposure, and very poor mental health reflected on measures of PTSD, SUD, suicidality and domains of social, emotional, behavioral and family functioning. There were few differences in clinical characteristics between the two groups.

Research limitations/implications

Similarity between the two groups suggests that the complex problems seen in emerging adults with PTSD + SUD are likely to have had their onset in adolescence or earlier and to have been present for several years by the time individuals present for treatment.

Originality/value

To the best of the authors’ knowledge, this is the first study to compare the demographic and clinical profiles of adolescents and emerging adults with PTSD + SUD. These findings yield important implications for practice and policy for this vulnerable group. Evidence-based prevention and early intervention approaches and access to care are critical. Alongside trauma-focused treatment, there is a critical need for integrated, trauma-informed approaches specifically tailored to young people with PTSD + SUD.
Myriad of quality challenges in the Koudiet Eddraouch GIS substation project in sub-Sahara Africa
Authors: Kumar Sunil , Shrivastava Ravindra
Published: June 2024

Learning outcomes

After completion of the case study, the participants will be able to understand the significance of quality as a pivotal domain within project management and to analyze the issues related to quality and offer logical solutions.

Case overview/synopsis

In this case, the Bharat Bijlee Construction Limited (BBCL) group, with a proven track record of over five decades in the transmission and distribution business in India, decided to venture into international projects, considering the prevailing stagnant domestic power sector. They secured contracts worth $85m from the “Shariket Karhaba Koudiet Eddraouch Spa,” a state-owned company responsible for power generation, transmission and distribution in Algeria. However, during the execution phase of these projects, BBCL encountered significant challenges related to product and service quality. These challenges arose due to the tight schedule constraints and cost considerations, as well as a lack of understanding of the dynamics involved in executing international projects, especially in the demanding conditions of the sub-Saharan desert. This case study addresses the complex issue of ensuring and maintaining high-quality standards in large-scale substation projects situated in the challenging environment of the sub-Saharan desert, highlighting the importance of effective project management and international project execution expertise. The case study is from quality management knowledge area and focuses on identification of root cause of quality noncompliance and for better decision-making in projects.

Complexity academic level

The teaching case is designed for undergraduate and postgraduate courses in project management, civil engineering and architecture domain. The participants will be able to understand the application of various quality tools, statistical process tools and control charts in problem identification, categorization, root cause identification and decision-making.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS2: Built environment
Impact pathways: technology-aided supply chain planning for resilience
Authors: Sengupta Sourav , Dreyer Heidi C. , Jonsson Patrik
Published: June 2024

Purpose

Due to emerging uncertainties, supply chain planning (SCP) has become complex for many companies, and practitioners are unsure how emerging technologies can help. We address this gap by identifying pathways of how digital technologies may aid planned flexibility in SCP.

Design/methodology/approach

The research builds on engaged scholarship and co-creation of knowledge. Eight senior managers from two companies participated in three rounds of workshops with us discussing and contrasting their planning challenges and potential solutions using examples of industry 4.0 applications drawn from the literature.

Findings

Based on a novel framework for digital transition in SCP, this research shows how emerging technologies may aid SCP in building resilience to emergent uncertainties and open new research avenues through four impact pathways.

Research limitations/implications

The SCP literature is ruefully short on studies that address technology-aided SC resilience. The research explains why this calls for a paradigm shift in SCP research.

Originality/value

This research argues that resilience-building SCP requires planned flexibility and presents a digital transition framework that allows for it.
Sports celebrities and advertising on Instagram: a case study of brand sponsorship in Spain
Authors: Gordillo-Rodriguez Maria-Teresa , Marín-Montín Joaquín , Fernández Gómez Jorge David
Published: June 2024

Purpose

The aim of this paper, which analyses the use of sports celebrities in advertising discourse, is to understand the strategic use to which brands put them in their commercial and corporate communication on Instagram.

Design/methodology/approach

To this end, a content analysis was performed on the Instagram posts of the brands Santander, Movistar, Red Bull and Iberdrola during the period 2021-2022.

Findings

The results indicate that, strategically speaking, these brands use the celebrity endorsement strategy to pursue emotional objectives and to adopt a position depending on the type of user. Likewise, these findings show that they single out uniqueness as the principal celebrity characteristic, while also mainly leveraging sports values, especially competence. These values represented by sports celebrities are markedly social in nature, which implies that they enjoy a degree of public recognition that is transferred to the brand to which they lend their image.

Research limitations/implications

The conclusions connect celebrity endorsers with strategic branding issues and aspects of sports.

Originality/value

An empirical approach is followed here to study the representation of sports celebrities in the advertising of well-known brands linked to the sports world.
Towards the recalibration of US dollar’s international dominance
Authors: Iliyasu Jamilu , Mamman Suleiman O , Abubakar Attahir Babaji
Published: June 2024

Purpose

This paper aims to examine the impact of United States (US) financial sanctions on the international dominance of the US dollar.

Design/methodology/approach

The survival analysis technique, which incorporates survival and hazard probabilities to determine the probability of central banks' reserve recalibration, is adopted for analysis.

Findings

The result shows that the probability of central banks recalibrating the dollar share of their official reserve currencies would increase by 60% for every ten additional financial sanctions by the United States. This could imply that more sanctions might have unintended consequences on the international reserve currency dominance of the US dollar.

Originality/value

To the best of the authors’ knowledge, this study may be a novel attempt to use survival analysis to examine the impact of financial sanctions on the US dollar’s international reserve currency dominance.
Unveiling frustration: an exploration of principals' frustration in special education schools for complex disabilities
Authors: Dor-Haim Peleg
Published: June 2024

Purpose

The study aims to explore the diverse meanings and sources of frustration among Israeli principals working in special education settings. The study poses two questions: 1. What are the perceived expressions of frustration among principals working in the context of special education? 2. What are the perceived sources of frustration among principals working in special education settings?

Design/methodology/approach

A total of 17 semi-structured interviews were conducted with principals working in special education schools for complex disabilities to investigate perceived expressions and sources of frustration.

Findings

The study identified four themes through data analysis: helplessness regarding the children, helplessness regarding bureaucratic aspects, frustration from conflicts and disappointment and frustration from feeling alone.

Originality/value

Despite the extensive acknowledgment of emotions and feelings in the context of educational leadership, the experience of work frustration among special education school principals has not been explicitly investigated. This research provides empirical insights into the nuanced experiences of frustration among special education principals, offering both empirical and practical implications for understanding and addressing this critical aspect of their work.
Authentic leadership, proactive goal regulation and help-seeking behavior: a multilevel moderated mediation
Authors: Wang Zhining , Zhou Xuan , Cai Shaohan
Published: June 2024

Purpose

Based on self-regulation theory, this study aims to investigate the relationship between authentic leadership and help-seeking behavior, as well as the mediating effect of proactive goal regulation and the moderating effect of leader identification.

Design/methodology/approach

We conducted a questionnaire survey on 489 employees from 94 teams and tested our research model through multi-level pathway analysis.

Findings

The analysis results suggest that (1) authentic leadership positively relates to employees’ proactive goal regulation; (2) employees’ proactive goal regulation positively relates to their autonomous (dependent) help-seeking behavior; (3) employees’ proactive goal regulation plays an intermediary role between authentic leadership and help-seeking behavior; (4) leader identification positively moderates the influence of authentic leadership on employees’ proactive goal regulation and (5) leader identification positively moderates the indirect relationship between authentic leadership and employees’ help-seeking behavior through employees’ proactive goal regulation.

Practical implications

Based on the findings of this study, organizations should foster authentic leadership in workplace to promote employees’ help-seeking behavior. In addition, managers should also attach importance to proactive goal regulation in promoting help-seeking behavior and leader identification in enhancing the positive influence of authentic leadership on employees’ proactive goal regulation.

Originality/value

This study finds that proactive goal regulation plays a key mediating role between authentic leadership and help-seeking behavior, and reveals the role of leader identification in reinforcing the positive impact of authentic leadership on help-seeking behavior.
Strategic insights into carbon markets, digital finance and geopolitical risks for advancing green sustainability investments
Authors: Mnif Emna , Jarboui Anis , Mouakhar Khaireddine
Published: June 2024

Purpose

Sustainable development hinges on a crucial shift to renewable energy, which is essential in the fight against global warming and climate change. This study explores the relationships between artificial intelligence (AI), fuel, green stocks, geopolitical risk, and Ethereum energy consumption (ETH) in an era of rapid technological advancement and growing environmental concerns.

Design/methodology/approach

This research stands at the forefront of interdisciplinary research and forges a path toward a comprehensive understanding of the intricate dynamics governing green sustainability investments. These objectives have been fulfilled by implementing the innovative quantile time-frequency connectedness approach in conjunction with geopolitical and climate considerations.

Findings

Our findings highlight coal market dominance and Ethereum energy consumption as critical short- and long-term market volatility sources. Additionally, geopolitical risks and Ethereum energy consumption significantly contribute to volatility. Long-term factors are the primary drivers of directional volatility spillover, impacting green stocks and energy assets over extended periods. Additionally, SHapley Additive exPlanations (SHAP) findings corroborate the quantile time-frequency connectedness outcomes.

Research limitations/implications

This study highlights the critical importance of transitioning to sustainable energy sources and embracing digital finance in fostering green sustainability investments, illuminating their roles in shaping market dynamics, influencing geopolitics and ensuring the long-term sustainability required to combat climate change effectively.

Practical implications

The study offers practical sustainability implications by informing green investment choices, strengthening risk management strategies, encouraging interdisciplinary cooperation and fostering digital finance innovations to promote sustainable practices.

Originality/value

The implementation of the quantile time-frequency connectedness approach, in line with considering geopolitical and climate factors, marks the originality of this paper. This approach allows for a dynamic analysis of connectedness across different distribution quantiles, providing a deeper understanding of variable interactions under varying market conditions.