bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Effect of an Acute Stressor in Laying Hens using Thermographic Imaging and Vocalisations
Authors: van den Heuvel Huib , Youssef Ali , Grat Lisette M , Neethirajan Suresh
Published: August 2022

The laying hen sector has multiple issues concerning the animal’s welfare. One crucial factor negatively impacts chicken welfare is stress. The conventional way of measuring and assessing chicken stress is time-consuming and subjective to the assessor. On the other hand, sensing and sensor technologies can be used to obtain objective, continuous and non-invasive/contactless measures of animal behavioural and physiological welfare indicators. The present study aims to investigate the use of thermographic imaging and microphones (sound) in obtaining objective indicators for acute stress in laying hens. During this study, 40 laying hens were stressed by opening an umbrella as a stressor starting from one day age until nine-weeks old. The birds were stressed every other day. Another 12 birds were housed in another cage. These birds were not stressed and served as a control group. The surface temperatures of the bird’s comb and beak decreased (1°C and 2.5°C respectively) in response to the applied stressor. This effect was only seen in the treatment group and not in the control birds. The number of vocalisations the birds produced significantly decreased shortly after stress. The number of calls in the stressed group decreased from 39.5 to 12.1 calls/minute, where the control group decreased from 27.8 to 22.5 calls/minute. It was hypothesized that the number of vocalisations would increase after stress. This difference could be due to the daily behavioural rhythm performed by the birds. The birds might naturally produce more calls at certain hours of the day because of certain behaviours they perform. Three different neural network algorithms were employed to differentiate between the vocalisation of stressed and the control group. This was done by converting the audio files to images and feeding them to the pretrained convolutional neural networks (CNN). The Resnet CNN had the highest categorising accuracy with an overall accuracy of 86 percent. The changes in surface temperature of the beak, comb, eye, and head, as well as the results from the audio analysis could serve as potential indicator for acute stress in laying hens. Future research is warranted to validate the methodologies and findings under different environmental conditions and stressors.
Gene Birth in a Model of Non-genic Adaptation
Authors: Mani Somya , Tlusty Tsvi
Published: August 2022

Background

Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization andde novogene birth. Particularly,de novogene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms that lead to functionalization are poorly understood, and estimated rates ofde novogene birth remain contentious. Here, we address this problem within a model that takes into account mutations and structural variation, allowing us to estimate the likelihood of emergence of new functions at non-functional loci.

Results

Assuming biologically reasonable mutation rates and mutational effects, we find that functionalization of non-genic loci requires the realization of strict conditions. This is in line with the observation that mostde novogenes are localized to the vicinity of established genes. Our model also provides an explanation for the empirical observation that emerging proto-genes are often lost despite showing signs of adaptation.

Conclusions

Our work elucidates the properties of non-genic loci that make them fertile for adaptation, and our results offer mechanistic insights into the process ofde novogene birth.
SARS-CoV-2-specific CD4+and CD8+T cell responses can originate from cross-reactive CMV-specific T cells
Authors: Pothast Cilia R , Dijkland Romy C , Thaler Melissa , Hagedoorn Renate S , Kester Michel GD , Wouters Anne K , Hiemstra Pieter S , van Hemert Martijn J , Gras Stephanie , Falkenburg JH Frederik , Heemskerk Mirjam HM
Published: August 2022

Detection of SARS-coronavirus-2 (SARS-CoV-2) specific CD4+and CD8+T cells in SARS-CoV-2-unexposed donors has been explained by the presence of T cells primed by other coronaviruses. However, based on the relative high frequency and prevalence of cross-reactive T cells, we hypothesized CMV may induce these cross-reactive T cells. Stimulation of pre-pandemic cryo-preserved PBMCs with SARS-CoV-2 peptides revealed that frequencies of SARS-CoV-2-specific T cells were higher in CMV-seropositive donors. Characterization of these T cells demonstrated that membrane-specific CD4+and spike-specific CD8+T cells originate from cross-reactive CMV-specific T cells. Spike-specific CD8+T cells recognize SARS-CoV-2 spike peptide FVSNGTHWF (FVS) and dissimilar CMV pp65 peptide IPSINVHHY (IPS) presented by HLA-B*35:01. These dual IPS/FVS-reactive CD8+T cells were found in multiple donors as well as severe COVID-19 patients and shared a common T cell receptor (TCR), illustrating that IPS/FVS-cross-reactivity is caused by a public TCR. In conclusion, CMV-specific T cells cross-react with SARS-CoV-2, despite low sequence homology between the two viruses, and may contribute to the pre-existing immunity against SARS-CoV-2.
Deep-SMOLM: Deep Learning Resolves the 3D Orientations and 2D Positions of Overlapping Single Molecules with Optimal Nanoscale Resolution
Authors: Wu Tingting , Lu Peng , Rahman Md Ashequr , Li Xiao , Lew Matthew D.
Published: August 2022

Dipole-spread function (DSF) engineering reshapes the images of a microscope to maximize the sensitivity of measuring the 3D orientations of dipole-like emitters. However, severe Poisson shot noise, overlapping images, and simultaneously fitting high-dimensional information–both orientation and position–greatly complicates image analysis in single-molecule orientation-localization microscopy (SMOLM). Here, we report a deep-learning based estimator, termed Deep-SMOLM, that archives superior 3D orientation and 2D position measurement precision within 3% of the theoretical limit (3.8◦ orientation, 0.32 sr wobble angle, and 8.5 nm lateral position using 1000 detected photons). Deep-SMOLM also achieves state-of-art estimation performance on overlapping images of emitters, e.g., a 0.95 Jaccard index for emitters separated by 139 nm, corresponding to a 43% image overlap. Deep-SMOLM accurately and precisely reconstructs 5D information of both simulated biological fibers and experimental amyloid fibrils from images containing highly overlapped DSFs, at a speed ∼10 times faster than iterative estimators.
Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels
Authors: Kern David M. , Bleier Julia , Mukherjee Somnath , Hill Jennifer M. , Kossiakoff Anthony A. , Isacoff Ehud Y. , Brohawn Stephen G.
Published: August 2022

Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (Swell1) and LRRC8B-E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents implicated in a broad range of physiology. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here, we leverage a fiducial-tagging strategy to determine single-particle cryo-electron microscopy structures of heterohexameric LRRC8A:C channels in detergent micelles and lipid nanodiscs in three conformations. LRRC8A:C channels show pronounced changes in channel architecture compared to homomeric channels due to heterotypic cytoplasmic LRR interactions that displace LRRs and the LRRC8C subunit away from the conduction axis and poise the channel for activation. The structures and associated functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. Together, our results provide insight into determinants for heteromeric LRRC8 channel assembly, activity, and gating by lipids.
A nuclear jamming transition in vertebrate organogenesis
Authors: Kim Sangwoo , Amini Rana , Campàs Otger
Published: August 2022

Jamming of cell collectives and associated rigidity transitions have been shown to play a key role in tissue dynamics, structure and morphogenesis. In cellular jamming, the physical state of the tissue is controlled by cellular density and the mechanics of cell-cell contacts. A potential contribution of subcellular organelles to the emergent tissue mechanics and architecture, as well as in the control of rigidity transitions, has not been explored. Here we show the existence of a nuclear jamming transition in which jamming of nuclei constrains cell movements beyond cellular jamming, with physical interactions between nuclei controlling the emergent physical properties and architecture of the tissue. We develop a computational framework and show that nuclear volume fraction and nuclear anisotropy are key parameters to understand the emergent tissue physical state. Analysis of tissue architecture during eye and brain development in zebrafish shows that these tissues undergo a nuclear jamming transition as they form, with increasing nuclear packing leading to more ordered cellular arrangements, reminiscent of the crystalline cellular packings in the functional adult eye. Our results reveal a novel rigidity transition associated with nuclear jamming, and highlight an important role for the nucleus in the control of emergent tissue mechanics and architecture.
Viral and Symptom Rebound in Untreated COVID-19 Infection
Authors: Deo Rinki , Choudhary Manish C. , Moser Carlee , Ritz Justin , Daar Eric S. , Wohl David A. , Greninger Alexander L. , Eron Joseph J. , Currier Judith S. , Hughes Michael D. , Smith Davey M. , Chew Kara W. , Li Jonathan Z. ,   the ACTIV-2/A5401 Study Team
Published: August 2022

Background

There are reports of viral RNA and symptom rebound in people with COVID-19 treated with nirmatrelvir/ritonavir. Since the natural course of viral and symptom trajectories of COVID-19 has not been well described, we evaluated the incidence of viral and symptom rebound in untreated outpatients with mild-moderate COVID-19.

Methods

The study population included 568 participants enrolled in the ACTIV-2/A5401 platform trial who received placebo. Anterior nasal swabs were collected for SARS-CoV-2 RNA testing on days 0-14, 21 and 28. Participants recorded the severity of 13 targeted symptoms daily from day 0 to 28. Viral rebound was defined as ≥0.5 log10 viral RNA copies/mL increase and symptom rebound was defined as a 4-point total symptom score increase from baseline. Baseline was defined as study day 4 (primary analysis) or 8 days from symptom onset (secondary analysis).

Findings

In both the primary and secondary analyses, 12% of participants had viral rebound. Viral rebounders were older than non-rebounders (median 54 vs 47 years, P=0.04). Symptom rebound occurred in 27% of participants after initial symptom improvement and in 10% of participants after initial symptom resolution. The combination of high-level viral rebound to ≥5.0 log10 RNA copies/mL and symptom rebound after initial improvement was observed in 1-2% of participants.

Interpretation

Viral RNA rebound or symptom relapse in the absence of antiviral treatment is common, but the combination of high-level viral and symptom rebound is rare.

Funding

This study was supported by the National Institute of Allergy and Infectious Diseases; ACTIV-2/A5401 ClinicalTrials.gov number NCT04518410.
Complex Temporal behavior Modeling for Pandemic Spread: Not a Simple Delayed Response!
Authors: Shahtori Narges M. , Atashzar S. Farokh
Published: August 2022

One of the significant challenges, when a new virus circulates in a host population, is to detect the outbreak as it arises in a timely fashion and implement the appropriate preventive policies to effectively halt the spread of the disease. The conventional computational epidemic models provide a state-space representation of the dynamic changes of various sub-clusters of a society based on their exposure to the virus and are mostly developed for small-size epidemics. In this work, we reshape and reformulate the conventional computational epidemic modeling approach based on the complex temporal behavior of disease propagation in host populations, inspired by the COVID-19 pandemic. Our new proposed framework allows the construction of transmission rate (p) as a probabilistic function of contributing factors such as virus mutation, immunity waning, and immunity resilience. Our results unravel the interplay between transmission rate, vaccination, virus mutation, immunity loss, and their indirect impacts on the endemic states and waves of the spread. The proposed model provides a robust mathematical framework that allows policy-makers to improve preparedness for curtailing an infectious disease and unfolds the optimal time-frame for vaccination given the available resources and the probability of virus mutation for the current and unforeseen outbreaks.
Mutational screens highlight glycosylation as a modulator of CSF3R activity
Authors: Hollander Michael J. , Malaker Stacy A. , Perez Idalia , Maxson Julia E. , Cochran Jennifer R. , Bertozzi Carolyn R.
Published: August 2022

The colony-stimulating factor 3 receptor (CSF3R) controls the growth of neutrophils, the most abundant type of white blood cell. In healthy neutrophils, signaling is dependent on CSF3R binding to its ligand CSF3. A single amino acid mutation in CSF3R, T618I, instead allows for constitutive, ligand-independent cell growth and leads to a rare type of cancer called chronic neutrophilic leukemia (CNL). We investigated why this threonine to isoleucine substitution is the predominant mutation in CNL and how it leads to uncontrolled neutrophil growth. Using protein domain mapping, we demonstrated that the single CSF3R domain containing residue 618 is sufficient for ligand-independent activity. We then applied an unbiased mutational screening strategy focused on this domain and found that activating mutations are enriched at sites normally occupied by asparagine, threonine, and serine residues – the three amino acids which are commonly glycosylated. We confirmed glycosylation at multiple CSF3R residues by mass spectrometry, including the presence of GalNAc and Gal-GalNAc glycans at wild-type threonine 618. Using the same approach applied to other cell surface receptors, we identified an activating mutation, S489F, in the interleukin-31 receptor alpha chain (IL-31Rα). Combined, these results suggest a role for glycosylated hotspot residues in regulating receptor signaling, mutation of which can lead to ligand-independent, uncontrolled activity.
SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses
Authors: Kohyama Masako , Suzuki Tatsuya , Nakai Wataru , Ono Chikako , Matsuoka Sumiko , Iwatani Koichi , Liu Yafei , Sakai Yusuke , Nakagawa Atsushi , Tomii Keisuke , Ohmura Koichiro , Okada Masato , Matsuura Yoshiharu , Ohshima Shiro , Maeda Yusuke , Okamoto Toru , Arase Hisashi
Published: August 2022

Many patients with severe COVID-19 suffer from pneumonia, and thus elucidation of the mechanisms underlying the development of such severe pneumonia is important. The ORF8 protein is a secreted protein of SARS-CoV-2, whose in vivo function is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2. We found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrate that the serum ORF8 protein levels are correlated well with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a viral cytokine of SARS-CoV-2 involved in the in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients.
Free energy perturbation calculations of mutation effects on SARS-CoV-2 RBD::ACE2 binding affinity
Authors: Sergeeva Alina P. , Katsamba Phinikoula S. , Sampson Jared M. , Bahna Fabiana , Mannepalli Seetha , Morano Nicholas C. , Shapiro Lawrence , Friesner Richard A. , Honig Barry
Published: August 2022

The strength of binding between human angiotensin converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of viral spike protein plays a role in the transmissibility of the SARS-CoV-2 virus. In this study we focus on a subset of RBD mutations that have been frequently observed in infected individuals and probe binding affinity changes to ACE2 using surface plasmon resonance (SPR) measurements and free energy perturbation (FEP) calculations. Our SPR results are largely in accord with previous studies but discrepancies do arise due to differences in experimental methods and to protocol differences even when a single method is used. Overall, we find that FEP performance is superior to that of other computational approaches examined as determined by agreement with experiment and, in particular, by its ability to identify stabilizing mutations. Moreover, the calculations successfully predict the observed cooperative stabilization of binding by the Q498R N501Y double mutant present in Omicron variants and offer a physical explanation for the underlying mechanism. Overall, our results suggest that despite the significant computational cost, FEP calculations may offer an effective strategy to understand the effects of interfacial mutations on protein-protein binding affinities and in practical applications such as the optimization of neutralizing antibodies.
Epitranscriptomic N6-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells
Authors: Phillips Stacia , Khadka Shaubhagya , Bohan Dana , Espada Constanza E. , Maury Wendy , Wu Li
Published: August 2022

N6-methyladenosine (m6A) is a dynamic post-transcriptional RNA modification that plays an important role in determining transcript fate. Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused the global pandemic of coronavirus disease 2019 (COVID-19) and the virus has been extensively studied. However, how m6A modification of host cell RNAs change during SARS-CoV-2 infection has not been reported. Here we define the epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells compared to uninfected controls. Biological pathway analyses revealed that differentially methylated transcripts were significantly associated with cancer-related pathways, protein processing in the endoplasmic reticulum, cell death and proliferation. Upstream regulators predicted to be associated with the proteins encoded by differentially methylated mRNAs include proteins involved in the type I interferon response, inflammation, and cytokine signaling. These data suggest that m6A modification of cellular RNA is an important mechanism of regulating host gene expression during SARS-CoV-2 infection of lung epithelial cells.
Discovery of RNA polymerase α-subunit protein as a novel quorum sensing reprograming factor inPseudomonas aeruginosa
Authors: Cai Wenjie , Liao Huimin , Lu Mingqi , Zhou Xiangting , Cheng Xiaoyan , Staehelin Christian , Dai Weijun
Published: August 2022

LasR is a master regulator of quorum-sensing (QS) inPseudomonas aeruginosa.LasR-null mutants commonly appear in lung isolates from chronically infected cystic fibrosis (CF) patients. However, numerous such CF isolates have a QS-active phenotype, but factors underlying QS-reprogramming in LasR-null mutants remain largely unknown. Mutations in the transcriptional regulator genemexTare well known to be responsible for QS-reprogramming in a laboratory LasR-null mutant strain, however, simultaneous occurrence oflasRandmexTmutations is rare in CF isolates. To identify QS-reprogramming determinants, we developed an experimental evolution approach, for which a QS-inactive LasR null mutant with an extra copy ofmexTwas engineered. In such a strain, spontaneous singlemexTmutations are expected to have no or little phenotypic consequences. This novel method, named “targeted gene duplication followed by mutant screening” (TGD-MS), resulted in the identification of QS-active revertants with mutations in genes other thanmexT. We characterized a QS-active revertant with a point mutation inrpoA,a gene encoding the α-subunit of RNA polymerase. QS activation in this mutant was found to be associated with the down-regulated expression ofmexEF-oprNefflux pump genes. Our study therefore uncovers a new functional role for RpoA in regulating QS activity. Furthermore, our results suggest that a regulatory circuit controlling the expression of themexEF-oprNoperon is critical for QS-reprogramming. In conclusion, our study reports on the identification of non-MexT proteins associated with QS-reprogramming in a laboratory strain, shedding light on possible QS activation mechanisms in clinicalP. aeruginosaisolates.
The Molecular Structure of Anterograde Intraflagellar transport trains
Authors: Lacey Samuel E. , Foster Helen E. , Pigino Gaia
Published: August 2022

Anterograde intraflagellar transport trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFTA and IFTB proteins that link structural and signalling cargoes to microtubule motors for import into cilia. It remains unknown how the IFTA/B proteins are arranged into complexes and how these complexes polymerise into functional trains. Here, we usein situcryo-electron tomography and Alphafold2 protein structure predictions to generate the first molecular model of the entire anterograde train. We show how the conformation of both IFTA and IFTB is dependent on lateral interactions with neighbouring repeats, suggesting that polymerization is required to cooperatively stabilize the complexes. The retrograde dynein motor binding site is a composite surface involving multiple IFTB repeats, ensuring that dynein can only form a strong interaction with IFTB upon train assembly. Finally, we reveal how IFTB extends two flexible tethers to maintain a connection with IFTA that can withstand the mechanical stresses present in actively beating cilia. Overall, our findings provide a framework for understanding the fundamental processes that are involved in cilia assembly.
Quantifying the contribution of subject and group factors in brain activation
Authors: Nakuci Johan , Yeon Jiwon , Xue Kai , Kim Ji-Hyun , Kim Sung-Phil , Rahnev Dobromir
Published: August 2022

Research in neuroscience often assumes universal neural mechanisms, but increasing evidence points towards sizeable individual differences in brain activations. What remains unclear is the extent of the idiosyncrasy and whether different types of analyses are associated with different levels of idiosyncrasy. Here we develop a new method for addressing these questions. The method consists of computing the within-subject reliability and subject-to-group similarity of brain activations and submitting these values to a computational model that quantifies the relative strength of group- and subject-level factors. We apply this method to a perceptual decision-making task (N=50) and find that activations related to task, reaction time (RT), and confidence are influenced equally strongly by group- and subject-level factors. Both group- and subject-level factors are dwarfed by a noise factor, though higher levels of smoothing increases their contributions relative to noise. Overall, our method allows for the quantification of group- and subject-level factors of brain activations and thus provides a more detailed understanding of the idiosyncrasy levels in brain activations.
Estimating temporally variable selection intensity from ancient DNA data
Authors: He Zhangyi , Dai Xiaoyang , Lyu Wenyang , Beaumont Mark , Yu Feng
Published: August 2022

Novel technologies for recovering DNA information from archaeological and historical specimens have made available an ever-increasing amount of temporally spaced genetic samples from natural populations. These genetic time series permit the direct assessment of patterns of temporal changes in allele frequencies, and hold the promise of improving power for the inference of selection. Increased time resolution can further facilitate testing hypotheses regarding the drivers of past selection events such as the incidence of plant and animal domestication. However, studying past selection processes through ancient DNA (aDNA) still involves considerable obstacles such as postmortem damage, high fragmentation, low coverage and small samples. To circumvent these challenges, we introduce a novel Bayesian framework for the inference of temporally variable selection based on genotype likelihoods instead of allele frequencies, thereby enabling us to model sample uncertainties resulting from the damage and fragmentation of aDNA molecules. Also, our approach permits the reconstruction of the underlying allele frequency trajectories of the population through time, which allows for a better understanding of the drivers of selection. We evaluate its performance through extensive simulations and demonstrate its utility with an application to the ancient horse samples genotyped at the loci for coat colouration. Our results reveal that incorporating sample uncertainties can further improve the inference of selection.
Diversity, distribution, and expression of opsin genes in freshwater lakes
Authors: He Shaomei , Linz Alexandra M. , Stevens Sarah L.R. , Tran Patricia Q. , Moya-Flores Francisco , Oyserman Ben O. , Dwulit-Smith Jeffrey R. , Forest Katrina T. , McMahon Katherine D.
Published: August 2022

Microbial rhodopsins are widely distributed in aquatic environments and may significantly contribute to phototrophy and energy budgets in global oceans. However, the study of freshwater rhodopsins has been largely limited. Here, we explored the diversity, ecological distribution, and expression of opsin genes that encode the apoproteins of Type I rhodopsins in humic and clearwater lakes with contrasting physicochemical and optical characteristics. Using metagenomes and metagenome-assembled genomes, we recovered opsin genes from a wide range of taxa, mostly predicted to encode green light-absorbing proton pumps. Viral opsin and novel bacterial opsin clades were recovered. Opsin genes occurred more frequently in taxa from clearwater than from humic water, and opsins in some taxa have non-typical ion-pumping motifs that might be associated with physicochemical conditions of these two freshwater types. Analyses of the surface layer of 33 freshwater systems revealed an inverse correlation between opsin gene abundance and lake dissolved organic carbon (DOC). In humic water with high terrestrial DOC and light-absorbing humic substances, opsin gene abundance was low and dramatically declined within the first few meters, whereas the abundance remained relatively high along the bulk water column in clearwater lakes with low DOC, suggesting opsin gene distribution is influenced by lake optical properties and DOC. Gene expression analysis confirmed the significance of rhodopsin-based phototrophy in clearwater lakes and revealed different diel expressional patterns among major phyla. Overall, our analyses revealed freshwater opsin diversity, distribution and expression patterns, and suggested the significance of rhodopsin-based phototrophy in freshwater energy budgets, especially in clearwater lakes.
Mouse-embryo model derived exclusively from embryonic stem cells undergo neurulation and heart development
Authors: Lau Kasey Y.C. , Rubinstein Hernan , Gantner Carlos W. , Amadei Gianluca , Stelzer Yonatan , Zernicka-Goetz Magdalena
Published: August 2022

Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extra-embryonic lineages of the post-implantation embryo by transcription factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation, and formation of the anterior-posterior axis, brain, a beating heart structure, and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages, but also showed when and where the model diverges from the natural program. Our findings demonstrate an extra-ordinary plasticity of ESCs to self-organize and generate a whole embryo-like structure.
Single cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell deployment and progression
Authors: De Bono Christopher , Liu Yang , Ferrena Alexander , Valentine Aneesa , Zheng Deyou , Morrow Bernice E.
Published: August 2022

Disruption of cardiac neural crest cells (CNCCs) results in congenital heart disease, yet we do not understand the cell fate dynamics as these cells differentiate to vascular smooth muscle cells. Here we utilized single-cell RNA-sequencing of NCCs from the pharyngeal apparatus with heart in control mouse embryos and when Tbx1, the gene for 22q11.2 deletion syndrome, is inactivated. We uncovered three dynamic transitions of pharyngeal NCCs expressing Tbx2 and Tbx3 through differentiated CNCCs expressing cardiac transcription factors with smooth muscle genes, and that these transitions are altered non-autonomously by loss of Tbx1. Further, inactivation of Tbx2 and Tbx3 in early CNCCs resulted in aortic arch branching defects due to failed smooth muscle differentiation. Loss of Tbx1 interrupted mesoderm to CNCC cell-cell communication with upregulation of BMP signaling with reduced MAPK signaling and failed dynamic transitions of CNCCs leading to disruption of aortic arch artery formation and cardiac outflow tract septation.
Promoting inclusivity and acceptance of diverse sexual and gender identities in schools: a Rapid Realist Review of universal interventions to improve mental health
Authors: Schlief Merle , Stefanidou Theodora , Wright Talen , Levy Grace , Pitman Alexandra , Lewis Gemma
Published: August 2022

Background

Sexual minority and trans young people are more likely to experience depression, anxiety, self-harm and suicidality than their heterosexual or cisgender peers. Improving inclusivity and acceptance of diverse sexual and gender identities, through universal interventions in schools, could prevent these mental health problems. We reviewed evidence, and developed a conceptual framework, to explain which universal interventions work, for whom, in which contexts, and why.

Methods

We conducted a Rapid Realist Review, with a systematic search of published, peer-reviewed and grey literature. We included reports from a call for evidence and website searches. Data were extracted in Context-Mechanism-Outcome (CMO) configurations. CMOs were developed and refined through discussions with experts by lived experience including young people, teachers, school governors and policy representatives

Findings

We included 53 studies, and classified interventions into five themes: Gay-Straight Alliances or similar student clubs (e.g. pride clubs), inclusive anti-bullying and harassment policies, inclusive curricula, workshops, and staff training. These interventions have the potential to reduce mental health problems among sexual minority and trans young people by reducing discrimination, bullying and feelings of unsafety, exclusion and marginalisation. The interventions appear to work best when teaching staff and school leaders are properly trained, and the school climate and community are supportive. Interventions may be less effective for boys and trans and bisexual students.

Interpretation

Our findings provide guiding principles for schools to develop interventions to improve the mental health of sexual minority and trans students. These findings should encourage primary research to confirm, refute or refine our programme theories.
Structural variable validation of an Online Learning Response Behavior (OLRB) instrument: A comparison analysis of three extraction methods of Exploratory Factor Analysis
Authors: Azman Ong Mohd Hanafi , Mohd Yasin Norazlina , Ibrahim Nur Syafikah
Published: August 2022

Purpose

Measuring internal response of online learning is seen as fundamental to absorptive capacity which stimulates knowledge assimilation. However, the evaluation of practice and research of validated instruments that could effectively measure online learning response behavior is limited. Thus, in this study, a new instrument was designed based on literature to determine the structural variables that exist in the online learning response behavior.

Design/methodology/approach

A structured survey was designed and distributed to 410 Malaysian students enrolled in higher-education institutions. The questionnaire has 38 items, all of which were scored using a seven-point likert scale. To begin with, exploratory factor analysis with three types of extraction methods (i.e. principal component, principal axis factoring and maximum likelihood) was used as the method for comparing the outcomes of each extraction method's grouping variables by constantly using a varimax rotation method. In the second phase, reliability analysis was performed to determine the reliability level of the grouping variables, and finally, correlation analysis was performed to determine the discriminant nomological validity of the grouping variables.

Findings

The findings revealed that nine grouping variables were retrieved, with all items having a good value of factor loading and communalities, as well as an adequate degree of reliability. These extracted variables have good discriminant and nomological validity, as evidenced by correlation analysis, which confirmed that the directions of relationships among the extracted dimensions follow the expected theory (i.e. positive direction) and the correlation coefficient is less than 0.70.

Research limitations/implications

This study proposes a comprehensive set of questionnaires that measure the student's online learning response behavior. These questionnaires have been developed on the basis of an extensive literature review and have undergone a rigorous process of validity and reliability for the purpose of enhancing students' online learning response behavior.

Originality/value

This study's findings will aid academic practitioners in assessing the online learning response behavior of students, as well as enhancing the questionnaire's boost factor when administered in an online learning environment.
Exploring the income, savings and debt levels of autistic adults living in Australia
Authors: Cai Ru Ying , Gallagher Emma , Haas Kaaren , Love Abigail , Gibbs Vicki
Published: August 2022

Purpose

Many autistic adults experience unemployment, which may impact their financial circumstances. However, no research has examined their personal financial circumstances. Therefore, this study aims to examine the self-reported income, savings and debt of autistic adults living in Australia, as well as the demographic associates and predictors of income and savings.

Design/methodology/approach

Sixty-four autistic adults aged 18–67 years (Mage = 32.78, SDage = 11.36) completed an online survey containing questions relating to their financial circumstances and the autism spectrum quotient-short.

Findings

Overall, the authors found that many autistic adults are financially disadvantaged. The mode of income levels was below AU$25,000, which is substantially lower than the mean annual Australian full-time income of AU$89,123. Higher savings was associated with not having any debt or having a greater ability to repay debt. Autism traits were positively associated with income levels. As predicted, being employed was associated with and predicted higher income. People who were employed were four times more likely to have a higher income than unemployed individuals. The authors did not find a relationship between having a co-occurring mental condition with income or savings. The authors also did not find a significant association between employment status and savings.

Practical implications

These research findings have implications on how we can improve the financial circumstances of autistic adults and provide additional evidence for the importance of increasing employment opportunities for autistic individuals.

Originality/value

To the best of the authors’ knowledge, this is the first study to examine the personal financial circumstances of autistic adults.
The proxy of Dorian Gray: scientific realism, construct validation and the way forward
Authors: Rigdon Edward
Published: August 2022

Purpose

This paper aims to clarify some of the representations regarding philosophy of science and statistical methods, which are contained in Cadogan and Lee (this issue).

Design/methodology/approach

This paper uses logical argument and a review of literature.

Findings

Rigdon’s (2012) approach to construct validation is entirely consistent with scientific realism, while the “realist variable framework” revives the empiricist reification of common factors found in Bagozzi’s (1984) Holistic Construal and throughout the early literature of structural equation modeling. Factor indeterminacy is a phenomenon that makes it impossible to equate common factors with conceptual variables. The future of marketing measurement is not in the historical error-centric framework but in a measurement framework centered around uncertainty.

Research limitations/implications

Researchers should avoid reification of common factors and recognize the validity gap between conceptual variables and empirical proxies, consistent with Rigdon (2012) and should move toward an uncertainty-centric approach to measurement.

Practical implications

Decision-makers need to acknowledge the difference between data and the underlying reality. Success or failure will be shaped by the reality, not by the data.

Originality/value

To the best of the author’s knowledge, this is the first paper seeking to clarify representations in Cadogan and Lee (this issue). This paper aims to save journal readers from being misled.
When and how information and communication technology orientation affects salespeople’s role stress: the interplay of salesperson characteristics and environmental complexity
Authors: Kramer Victoria , Krafft Manfred
Published: August 2022

Purpose

As empirical insights into when salespeople should integrate information and communication technology (ICT) into their sales tasks are limited, the purpose of this study is to investigate the impact of salespeople’s ICT orientation on role stress by considering the interplay of individual salesperson characteristics and the complexity of the selling environment, differentiating between customer and supplier complexity.

Design/methodology/approach

The authors develop an empirical framework based on the Job Demands-Resources model and previous research in the area of technology in sales. They test their hypotheses by means of a survey of 255 business-to-business salespeople which is analyzed using ordinary least squares regressions.

Findings

The results of this study show that ICT orientation generally helps salespeople to reduce role ambiguity. However, the benefits salespeople derive from ICT orientation to reduce role conflict depend on an interplay of both their job tenure and the average relationship duration with customers as well as the complexity of the selling environment.

Originality/value

This study contributes to research on the impact of technology use on salespeople by enhancing the understanding of contexts that make ICT valuable for them. In particular, the findings of this study demonstrate that the impact of ICT orientation on salespeople’s role stress depends on an interplay of individual salesperson characteristics, that is, resources, and environmental complexity characteristics, that is, demands.
Corporate governance and capital structure in Latin America: empirical evidence
Authors: Borges Júnior Dermeval Martins
Published: August 2022

Purpose

This study aims to examine the relationship between corporate governance mechanisms and the capital structure of Latin American firms.

Design/methodology/approach

The sample included companies from Argentina, Brazil, Chile, Colombia, Mexico and Peru. The authors collected data from 201 non-financial companies between 2009 and 2018, totalizing 1,716 firm-year observations. The data were analyzed using descriptive statistics and linear regression models with panel data.

Findings

The main results indicated that chief executive officer duality, legal protection system and corporate social responsibility voluntary disclosure impact the firm's total debt ratio, corresponding to a positive effect for the first two variables and a negative for the last.

Originality/value

This study advances in two main ways. Firstly, due to the broad approach in which the authors addressed corporate governance, involving board composition, ownership structure, minority shareholders legal protection system and information disclosure. Secondly, by presenting empirical evidence about the effects of corporate governance on capital structure from an extensive sample of Latin American firms, the authors expect to contribute to the international debate on the capital structure due to the unique characteristics of Latin America in this regard.
The role of coworking spaces in the changing landscape of future workplace agility: linking boundary organization theory and organizational development models
Authors: Yang Eunhwa , Sanborn Bonnie Eaton , Zhou Yaoyi
Published: August 2022

Purpose

This study aims to illustrate the potential of coworking spaces as one way to achieve optimal workplace arrangements and corporate real estate (CRE) agility, especially for large organizations. The authors suggest understanding coworking spaces from the boundary organization theory and organizational growth model.

Design/methodology/approach

This study takes a threefold theoretical approach: conducting a literature review and identifying the gaps in coworking studies for large organizations, applying the organizational boundary theory in tandem with organizational growth models in the context of coworking spaces as a part of the workplace ecology and identifying future research agendas for coworking studies.

Findings

This study proposes a conceptual framework of how coworking spaces can be viewed and used as a boundary object throughout the organizational growth phases. Besides, four major future research areas are proposed: case studies and/or empirical evidence of coworking spaces as CRE buffer zones and boundary objects for organizations, coworking space design and different formats of boundary object-infused collaboration, coworking space design and management for its own agility and flexibility and how coworking affects employees’ performance, health and well-being and professional training/mentoring.

Practical implications

For large organizations, there is a clear pressure to rethink CRE to increase workplace agility, flexibility and resilience, much accelerated with the recent COVID-19 pandemic. Understanding the effective use of coworking spaces as a part of CRE portfolios will help enhance corporates’ state and ability to reassess, realign and replan their CRE portfolios.

Originality/value

Many existing studies about coworking spaces are based on observations and self-reported justification at an individual level. Whether and how coworking can benefit companies at an organizational level is largely unstudied and worth more attention. This study illustrates a new theoretical understanding of how coworking spaces can be a part of CRE portfolios and bring potential benefits of inter and intraorganizational collaboration throughout the phases of organizational growth.
Authentic leadership in a pandemic world: an exploratory study in the Indian context
Authors: Chully Arun Antony , Jose Jerin , M Luthufi
Published: August 2022

Purpose

The purpose of this paper is to explore the strategies that helps leaders be authentic in order to be able to respond proactively and become effective in helping their organisations they lead in the context of the COVID-19 pandemic.

Design/methodology/approach

Using a qualitative approach, 25 business leaders from diverse sectors were interviewed to understand what sustained them in an adverse context.

Findings

Results reveal various dimensions of authentic leadership in a disruptive environment. Authentic leaders have to exhibit distinct behaviours that stems from re-examining oneself to reaffirming organisational purpose. Reimagining the work is emerged as the newer dimension to the authentic leadership considering the context of COVID-19.

Practical implications

The results of the study provides insights for anyone leading organisations in today's disruptive business environment. The findings of this study can be used further to undertake quantitative studies to test professional relationships and understand the leadership strategies at different time frames.

Originality/value

This paper addresses the strategies that leaders successfully follow to withstand the COVID crisis and highlights the different roles and behaviours that helped leaders to address the crisis confidently.
Foreign market selection of suppliers through a novel REF-Sort technique
Authors: Aytekin Ahmet , Görçün Ömer Faruk , Ecer Fatih , Pamucar Dragan , Karamaşa Çağlar
Published: August 2022

Purpose

The present study aims to provide a practical and robust assessment technique for assessing countries' investability in global supply chains to practitioners. Thus, the proposed approach can help decision-makers evaluate and select appropriate countries in the expansion process of the global supply chains and reduce risks concerning country (market) selection.

Design/methodology/approach

The present study proposes a novel decision-making approach, namely the REF-Sort technique. The proposed approach has many valuable contributions to the literature. First, it has an efficient basic algorithm and can be applied to solve highly complicated decision-making problems without requiring advanced mathematical knowledge. Besides, some characteristics differentiate REF-Sort apart from other techniques. REF-Sort employs the value or value range that reflects the most typical characteristic of the relevant class in assignment processes. The reference values in REF-Sort and center profiles are similar in this regard. On the other hand, class references can be defined as ranges in REF-Sort. Secondary values, called successors, can also be employed to assign a value to the appropriate class. REF-Sort can also determine the reference and successor values/ranges independently of the decision matrix. In addition, the proposed model is a maximally stable and consistent decision-making tool, as it is resistant to the rank reversal problem.

Findings

The current papers' findings indicate that countries have different features concerning investment. Hence, the current paper pointed out that only 22% of the 95 countries are investable, whereas 19% are risky. Thus, decision-makers should make detailed evaluations using robust, powerful, and practical decision-making tools to make more reasonable and logical decisions concerning country selection.

Originality/value

The current paper proposes a novel decision-making approach to evaluate. According to the authors' information, the proposed model has been applied to evaluate investable countries for the global supply chains for the first time.