bluuebunny/crossref_metadata_2025 huggingface dataset:
Parameter and model recovery of reinforcement learning models for restless bandit problems
Authors: Danwitz Ludwig , Mathar David , Smith Elke , Tuzsus Deniz , Peters Jan
Published: October 2021

Multi-armed restless bandit tasks are regularly applied in psychology and cognitive neuroscience to assess exploration and exploitation behavior in structured environments. These models are also readily applied to examine effects of (virtual) brain lesions on performance, and to infer neurocomputational mechanisms using neuroimaging or pharmacological approaches. However, to infer individual, psychologically meaningful parameters from such data, computational cognitive modeling is typically applied. Recent studies indicate that softmax (SM) decision rule models that include a representation of environmental dynamics (e.g. the Kalman Filter) and additional parameters for modeling exploration and perseveration (Kalman SMEP) fit human bandit task data better than competing models. Parameter and model recovery are two central requirements for computational models: parameter recovery refers to the ability to recover true data-generating parameters; model recovery refers to the ability to correctly identify the true data generating model using model comparison techniques. Here we comprehensively examined parameter and model recovery of the Kalman SMEP model as well as nested model versions, i.e. models without the additional parameters, using simulation and Bayesian inference. Parameter recovery improved with increasing trial numbers, from around .8 for 100 trials to around .93 for 300 trials. Model recovery analyses likewise confirmed acceptable recovery of the Kalman SMEP model. Model recovery was lower for nested Kalman filter models as well as delta rule models with fixed learning rates.

Exploratory analyses examined associations of model parameters with model-free performance metrics. Random exploration, captured by the inverse softmax temperature, was associated with lower accuracy and more switches. For the exploration bonus parameter modeling directed exploration, we confirmed an inverse-U-shaped association with accuracy, such that both an excess and a lack of directed exploration reduced accuracy. Taken together, these analyses underline that the Kalman SMEP model fulfills basic requirements of a cognitive model.
Inhibiting adult neurogenesis differentially affects spatial learning in females and males
Authors: O’Leary Timothy P , Askari Baran , Lee Bonnie , Darby Kathryn , Knudson Cypress , Ash Alyssa M , Seib Desiree R , Espinueva Delane F , Snyder Jason S
Published: October 2021

Adult hippocampal neurogenesis has been implicated in the spatial processing functions of the hippocampus but ablating neurogenesis does not consistently lead to behavioral deficits in spatial tasks. Parallel studies have shown that adult-born neurons also regulate behavioral responses to stressful and aversive stimuli. We therefore hypothesized that spatial functions of adult-born neurons may be more prominent under conditions of stress, and may differ between males and females given established sex differences in stress responding. To test this we trained intact and neurogenesis-deficient rats in the spatial water maze at temperatures that vary in their degree of aversiveness. At standard temperatures (25°C) ablating neurogenesis did not alter learning and memory in either sex, consistent with prior work. However, in cold water (16°C), ablating neurogenesis had divergent sex-dependent effects: relative to intact rats, male neurogenesis-deficient rats were slower to escape and female neurogenesis-deficient rats were faster. Neurogenesis promoted temperature-related changes in search strategy in females, but it promoted search strategy stability in males. Females displayed greater recruitment of the dorsal hippocampus than males, particularly at 16°C. However, blocking neurogenesis did not alter activity-dependent immediate-early gene expression in either sex. Finally, morphological analyses of retrovirally-labelled neurons revealed greater experience-dependent plasticity in new neurons in males. Neurons had comparable morphology in untrained rats but 16°C training increased spine density, and 25°C training caused shrinkage of mossy fiber presynaptic terminals, specifically in males. Collectively, these findings indicate that neurogenesis functions in memory are prominent under conditions of stress, they provide the first evidence for sex differences in the behavioral function of newborn neurons, and they suggest possibly distinct roles for neurogenesis in cognition and mental health in males and females.
Xist spatially amplifies SHARP recruitment to balance chromosome-wide silencing and specificity to the X chromosome
Authors: Jachowicz Joanna W. , Strehle Mackenzie , Banerjee Abhik K. , Thai Jasmine , Blanco Mario R. , Guttman Mitchell
Published: October 2021

Although thousands of lncRNAs are encoded in mammalian genomes, their mechanisms of action are largely uncharacterized because they are often expressed at significantly lower levels than their proposed targets. One such lncRNA is Xist, which mediates chromosome-wide gene silencing on one of the two X chromosomes to achieve gene expression balance between males and females. How a limited number of Xist molecules can mediate robust silencing of a significantly larger number of target genes (∼1 Xist RNA: 10 gene targets) while maintaining specificity to genes on the X within each cell is unknown. Here, we show that Xist drives non-stoichiometric recruitment of the essential silencing protein SHARP (also called Spen) to amplify its abundance across the inactive X, including at regions not directly occupied by Xist. This amplification is achieved through concentration-dependent homotypic assemblies of SHARP on the X and is required for chromosome-wide silencing. We find that expressing Xist at higher levels leads to increased localization at autosomal regions, demonstrating that low levels of Xist are critical for ensuring its specificity to the X chromosome. We show that Xist (through SHARP) acts to suppress production of its own RNA which may act to constrain overall RNA levels and restrict its ability to spread beyond the X. Together, our results demonstrate a spatial amplification mechanism that allows Xist to achieve two essential but countervailing regulatory objectives: chromosome-wide gene silencing and specificity to the X. Our results suggest that this spatial amplification mechanism may be a more general mechanism by which other low abundance lncRNAs can balance specificity to, and robust control of, their regulatory targets.
Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates
Authors: Walters Jewell N. , Schouest Blake , Patel Ami , Reuschel Emma L. , Schultheis Katherine , Parzych Elizabeth , Maricic Igor , Gary Ebony N. , Purwar Mansi , Andrade Viviane M. , Doan Arthur , Elwood Dustin , Eblimit Zeena , Nguyen Brian , Frase Drew , Zaidi Faraz I. , Kulkarni Abhijeet , Generotti Alison , Kim J Joseph , Humeau Laurent M. , Ramos Stephanie J. , Smith Trevor R.F. , Weiner David B. , Broderick Kate E.
Published: October 2021

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.
Biology-inspired data-driven quality control for scientific discovery in single-cell transcriptomics
Authors: Subramanian Ayshwarya , Alperovich Mikhail , Yang Yiming , Li Bo
Published: October 2021

Quality control (QC) of cells, a critical step in single-cell RNA sequencing data analysis, has largely relied on arbitrarily fixed data-agnostic thresholds on QC metrics such as gene complexity and fraction of reads mapping to mitochondrial genes. The few existing data-driven approaches perform QC at the level of samples or studies without accounting for biological variation in the commonly used QC criteria. We demonstrate that the QC metrics vary both at the tissue and cell state level across technologies, study conditions, and species. We propose data-driven QC (ddqc), an unsupervised adaptive quality control framework that performs flexible and data-driven quality control at the level of cell states while retaining critical biological insights and improved power for downstream analysis. On applyingddqcto 6,228,212 cells and 835 mouse and human samples, we retain a median of 39.7% more cells when compared to conventional data-agnostic QC filters. Withddqc, we recover biologically meaningful trends in gene complexity and ribosomal expression among cell-types enabling exploration of cell states with minimal transcriptional diversity or maximum ribosomal protein expression. Moreover,ddqcallows us to retain cell-types often lost by conventional QC such as metabolically active parenchymal cells, and specialized cells such as neutrophils or gastric chief cells. Taken together, our work proposes a revised paradigm to quality filtering best practices - iterative QC, providing a data-driven quality control framework compatible with observed biological diversity.
A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity
Authors: Gómez-Carballa Alberto , Rivero-Calle Irene , Pardo-Seco Jacobo , Gómez-Rial José , Rivero-Velasco Carmen , Rodríguez-Núñez Nuria , Barbeito-Castiñeiras Gema , Pérez-Freixo Hugo , Cebey-López Miriam , Barral-Arca Ruth , Rodriguez-Tenreiro Carmen , Dacosta-Urbieta Ana , Bello Xabier , Pischedda Sara , Currás-Tuala María José , Viz-Lasheras Sandra , Martinón-Torres Federico , Salas Antonio ,   GEN-COVID (www.gencovid.eu) study group
Published: October 2021

Background

COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences.

Methods and findings

We carried out a multi-tissue (nasal, buccal and blood;n= 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients.

Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis.

Conclusions

We found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.
Transferability of Psychological Interventions from Disaster-Exposed Employees to Healthcare Workers Working during the COVID-19 Pandemic
Authors: Treacy Sean , O’Donnell Shane , Gavin Blánaid , Schloemer Tamara , Quigley Etain , Adamis Dimitrios , Nicholas Fiona Mc , Hayden John C.
Published: October 2021

Background

The COVID-19 Pandemic had a significant negative impact on the mental health of healthcare workers. Evidence-based interventions that could be used to mitigate this impact are lacking in the literature. This review aims to evaluate psychological interventions used for employees following previous disasters and assess the transferability of these interventions to a healthcare setting during the COVID-19 pandemic.

Methods

Intervention information from a previously published systematic review of the literature published up to 2015 was extracted, and an additional search of studies published from 2015-2020 was conducted. Studies were assessed for transferability using a checklist derived from the PIET-T process model.

Results

Interventions from eighteen studies were assessed for transferability (including three studies identified in an updated literature search). Interventions established as most transferable included resilience training, meditation/mindfulness interventions, and cognitive behavioural therapy. Psychological debriefing was transferable but as it is contrary to current recommendations is not deemed appropriate for adoption.

Implications

Several existing interventions have the potential to be utilised within the COVID-19 context/pandemic. More research needs to be undertaken in this area to assess these interventions upon transfer.
The impact of epistasis in the heterosis and combining ability analyses
Authors: Viana José Marcelo Soriano
Published: October 2021

The current theoretical knowledge concerning the influence of epistasis on heterosis is based on simplified multiplicative model. The objective of this study was to assess the impact of epistasis in the heterosis and combining ability analyses, assuming additive model, hundreds of genes, linkage disequilibrium (LD), dominance, and seven types of digenic epistasis. We developed the quantitative genetics theory for supporting the simulation of the individual genotypic values in nine populations, the selfed populations, the 36 interpopulation crosses, 180 doubled haploids (DHs) and their 16,110 crosses, assuming 400 genes in 10 chromosomes of 200 cM. Epistasis only affects population heterosis if there is LD. Only additive x additive and dominance x dominance epistasis can affect the components of the heterosis and combining ability analyses of populations. Both analyses can lead to completely wrong inferences regarding the identification of the superior populations, the populations with greater differences of gene frequencies, and the populations with maximum variability, when the number of interacting genes and the magnitude of the epistatic effects are high. There was a decrease in the average heterosis by increasing the number of epistatic genes and the magnitude of their epistatic effects. The same results are generally true for the combining ability analysis of DHs. Surprisingly, the combining ability analyses of subsets of 20 DHs showed no significant average impact of epistasis on the identification of the most divergent ones, even assuming a high number of epistatic genes and great magnitude of their effects. However, a significant negative effect can occur.

Statements and Declarations

The author has no relevant financial or non-financial interests to disclose. The author has no competing interests to declare that are relevant to the content of this article. The author certifies that he has no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The author has no financial or proprietary interests in any material discussed in this article.
The Loroxanthin cycle: A new type of xanthophyll cycle in green algae (Chlorophyta)
Authors: van den Berg T E , Croce R.
Published: October 2021

Xanthophyll cycles have proven to be major contributors to photoacclimation for many organisms. This work describes a light-driven xanthophyll cycle operating in the chlorophyte Chlamydomonas reinhardtii and involving the xanthophylls Lutein (L) and Loroxanthin (Lo). Pigments were quantified during a switch from high to low light and at different time points from cells grown in Day/night cycle. Trimeric LHCII was purified from cells acclimated to high or low light and their pigment content and spectroscopic properties were characterized. The Lo/(L+Lo) ratio in the cells varies by a factor of 10 between cells grown in low or high light leading to a change in the Lo/(L+Lo) ratio in trimeric LHCII from 0.5 in low light to 0.07 in high light. Trimeric LhcbMs binding Loroxanthin have 5±1% higher excitation energy transfer from carotenoid to Chlorophyll as well as higher thermo- and photostability than trimeric LhcbMs that only bind Lutein. The Loroxanthin cycle operates on long time scales (hours to days) and likely evolved as a shade adaptation. It has many similarities with the Lutein-epoxide - Lutein cycle of plants.
ACTN2mutant causes proteopathy in human iPSC-derived cardiomyocytes
Authors: Zech Antonia T. L. , Prondzynski Maksymilian , Singh Sonia R. , Orthey Ellen , Alizoti Erda , Busch Josefine , Madsen Alexandra , Behrens Charlotta S. , Mearini Giulia , Lemoine Marc D. , Krämer Elisabeth , Mosqueira Diogo , Virdi Sanamjeet , Indenbirken Daniela , Depke Maren , Salazar Manuela Gesell , Völker Uwe , Braren Ingke , Pu William T. , Eschenhagen Thomas , Hammer Elke , Schlossarek Saskia , Carrier Lucie
Published: October 2021

Genetic variants in α-actinin-2 (ACTN2) are associated with several forms of (cardio)myopathy. We previously reported a heterozygous missense (c.740C>T)ACTN2gene variant, associated with hypertrophic cardiomyopathy, and characterized by an electro-mechanical phenotype in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Here, we created with CRISPR/Cas9 genetic tools two heterozygous functional knock-out hiPSC lines with a second wild-type (ACTN2wt) and missense ACTN2 (ACTN2mut) allele, respectively. We evaluated their impact on cardiomyocyte structure and function, using a combination of different technologies, including immunofluorescence and live cell imaging, RNA-seq, and mass spectrometry. This study showed that ACTN2mut present a higher percentage of multinucleation, protein aggregation, hypertrophy, myofibrillar disarray and activation of both the ubiquitin-proteasome system and the autophagy-lysosomal pathway as compared to ACTN2wt in 2D-cultured hiPSC-CMs. Furthermore, the expression of ACTN2mut was associated with a marked reduction of sarcomere-associated protein levels in 2D-cultured hiPSC-CMs and force impairment in engineered heart tissues. In conclusion, our study highlights the activation of proteolytic systems in ACTN2mut hiPSC-CMs likely to cope with ACTN2 aggregation and therefore directs towards proteopathy as an additional cellular pathology caused by thisACTN2variant, which may contribute to humanACTN2-associated cardiomyopathies.
Tubular lysosome induction couples animal starvation to healthy aging
Authors: Villalobos Tatiana V. , Ghosh Bhaswati , Alam Sanaa , Butsch Tyler J. , Mercola Brennan M. , Ramos Cara D. , Das Suman , Eymard Eric D. , Bohnert K. Adam , Johnson Alyssa E.
Published: October 2021

Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans, we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging.

One-Sentence Summary

Tubular lysosome induction promotes healthy aging.
Salmonella exploits OmpR to switch essential morphogenetic peptidoglycan synthases in response to intracellular cues
Authors: López-Escarpa David , Castanheira Sónia , García-del Portillo Francisco
Published: October 2021

Essential peptidoglycan synthases, like penicillin binding proteins 2 and 3 (PBP2/PBP3) of Escherichia coli, define shape by orchestrating cell elongation and division, respectively. Despite being intensively studied as drug targets, the regulatory rules governing their production remain poorly understood. During infection, the closely related pathogen Salmonella enterica serovar Typhimurium downregulates PBP2/PBP3 production and replace them with alternative peptidoglycan synthases, PBP2SAL/PBP3SAL, absent in E. coli. The bases for such switch in morphogenetic proteins are unknown. Here, we show that the S. Typhimurium regulator OmpR triggers PBP2SAL and PBP3SAL expression responding solely to acid pH and define a shared motif present in upstream regions of the PBP2SAL- and PBP3SAL-coding genes sufficient for such control. The elimination of PBP2/PBP3 in infection conditions is however multifactorial, requiring acidity, high osmolarity and being favoured by OmpR and the Prc protease. Remarkably, we found that E. coli loses the essential PBP3 required for cell division when exposed to both acidity and high osmolarity, the environmental cues encountered by intracellular S. Typhimurium. Therefore, OmpR played a central role in the evolution of this pathogen when co-opting the regulation of PBP2SAL/PBP3SAL and, consequently, promoting a new morphogenetic cycle that made possible increasing progeny inside acidic eukaryotic phagosomes.

Significance

Some enzymes that participate in peptidoglycan metabolism are present exclusively in bacterial pathogens and modify its structure to limit immune recognition. The intracellular pathogen Salmonella enterica serovar Typhimurium is the only example known to date in which a “substitution” of essential peptidoglycan enzymes involved in cell division and elongation takes place during infection. The data presented here support instability of PBP3 in environments with acidity and high osmolarity as a probable selective pressure that promoted the fixation of alternative morphogenetic enzymes. This was possible due to the control that OmpR exerted over these new foreign functions. The acquisition of enzymes like PBP2SAL and PBP3SAL therefore represent a “quantum leap” evolutionary event in S. Typhimurium that made possible the colonization of acidic intracellular niches.
Emergence of robust global modules from local interactions and smooth gradients
Authors: Khona Mikail , Chandra Sarthak , Fiete Ila
Published: October 2021

Modular structure and function are ubiquitous in biology, from the scale of ecosystems to the organization of animal bodies and brains. However, the mechanisms of modularity emergence over development remain unclear. Here we introduce the principle ofpeak selection, a process in which two local interactions self-organize discontinuous module boundaries from a smooth global gradient, unifying the positional hypothesis and the Turing pattern formation hypothesis for morphogenesis. Applied to the brain’s grid cell networks, peak selection results in the spontaneous emergence of functionally distinct modules with discretely spaced spatial periods. Applied to ecological systems, a generalization of the process results in discrete systems-level niches. The dynamics exhibits emergent self-scaling to variations in system size and “topological robustness” [1] that renders module emergence and module properties insensitive to most parameters. Peak selection substantially ameliorates the fine-tuning requirement of continuous attractor dynamics even within single modules. It makes a detail-independent prediction that grid module period ratios should approximate adjacent integer ratios, furnishing the most accurate match to data to date, with additional predictions to connect physiology, connectomics, and transcriptomics data. In sum, our results indicate that local competitive interactions combined with low-information global gradients can lead to robust global module emergence.
Investigating pathogenicity and virulence of Staphylococcus pettenkoferi: an emerging pathogen
Authors: Plumet Lucile , Ahmad-Mansour Nour , Huc-Brandt Sylvaine , Magnan Chloé , Yahiaoui-Martinez Alex , Kissa Karima , Pantel Alix , Lavigne Jean-Philippe , Molle Virginie
Published: October 2021

Staphylococcus pettenkoferi is a coagulase-negative Staphylococcus identified in 2002 that has been implicated in human diseases as an opportunistic pathogenic bacterium. Its multiresistant character is becoming a major health problem, yet the pathogenicity of S. pettenkoferi is poorly characterized. In this study, pathogenicity of a S. pettenkoferi clinical isolate from diabetic foot osteomyelitis was compared to a Staphylococcus aureus strain in various in vitro and in vivo experiments. Growth kinetics were compared against S. aureus and bacteria survival was assessed in the RAW 264.7 murine macrophage cell line, the THP-1 human leukemia monocytic cell line and the HaCaT human keratinocyte cell line. Ex vivo analysis were performed in whole blood survival assays, and in vivo assays via the infection model of zebrafish embryos. Moreover, whole-genome analysis was performed. Our results showed that S. pettenkoferi was able to survive in human blood, human keratinocytes, murine macrophages, and human macrophages. S. pettenkoferi demonstrated its virulence by causing substantial embryo mortality in the zebrafish model. Genomic analysis revealed virulence factors such as biofilm- (e.g., icaABCD; rsbUVW) and regulator- (e.g., agr, mgrA, sarA, saeS) encoding genes well characterized in S. aureus. This study thus advances the knowledge of this under investigated pathogen and validates the zebrafish infection model for this bacterium.
Mecp2 deletion results in profound alterations of developmental and adult functional connectivity
Authors: Rahn Rachel M. , Yen Allen , Chen Siyu , Gaines Seana H. , Bice Annie R. , Brier Lindsey M. , Swift Raylynn G. , Lee LeiLani , Maloney Susan E. , Culver Joseph P. , Dougherty Joseph D.
Published: October 2021

As a regressive neurodevelopmental disorder with a well-established genetic cause, Rett Syndrome and its Mecp2 loss-of-function mouse model provide an excellent opportunity to define potentially translatable functional signatures of disease progression, as well as offer insight into Mecp2’s role in functional circuit development. Thus, we applied optical fluorescence imaging to assess mesoscale calcium functional connectivity (FC) in the Mecp2 cortex prior to symptom onset as well as during decline. We found that FC was profoundly disrupted in Mecp2 males both in juvenile development and early adulthood. Female Mecp2 mice displayed a subtle homotopic contralateral increase in motor cortex as juveniles but not in adulthood, where instead parietal regions were implicated. Additionally, conditional rescue studies indicated FC phenotypes are driven by excitatory neurons. Altogether, the female results identify subtle candidate translatable biomarkers of disease progression, while the male results indicate MeCP2 protein is needed in a circuit-specific manner for FC.
Defined microenvironments trigger in vitro gastrulation in human pluripotent stem cells
Authors: Srivastava Pallavi , Romanazzo Sara , Ireland Jake , Nemec Stephanie , Molley Thomas G. , Jayathilaka Pavithra , Pandzic Elvis , Yeola Avani , Chandrakanthan Vashe , Pimanda John , Kilian Kristopher
Published: October 2021

Embryogenesis is orchestrated through local morphogen gradients and endometrial constraints that give rise to the three germ layers in a well-defined assembly. In vitro models of embryogenesis have been demonstrated by treating pluripotent stem cells in adherent or suspension culture with soluble morphogens and small molecules, which leads to tri-lineage differentiation. However, treatment with exogenous agents override the subtle spatiotemporal changes observed in vivo that ultimately underly the human body plan. Here we demonstrate how microconfinement of pluripotent stem cells on hydrogel substrates catalyses gastrulation-like events without the need for supplements. Within six hours of initial seeding, cells at the boundary show elevated cytoskeletal tension and yes-associated protein (YAP) activity, which leads to changes in cell and nuclear morphology, epithelial to mesenchymal transition, and emergence of defined patterns of primitive streak containing SRY-Box Transcription Factor 17 (SOX17)+ T/BRACHYURY+ cells. Immunofluorescence staining, transcript analysis, and the use of pharmacological modulators reveal a role for mechanotransduction-coupled non-canonical wingless-type (WNT) signalling in promoting epithelial to mesenchymal transition and multilayered organization within the colonies. These microscale gastruloids were removed from the substrate and encapsulated in 3D hydrogels, where biomaterials properties correspond to maintenance and spatial positioning of the primitive streak. Together, this approach demonstrates how materials alone can nurture embryonic gastrulation, thereby providing an in vitro model of early development.
Insights into Early Word Comprehension: Tracking the Neural Representations of Word Semantics in Infants
Authors: Saha Rohan , Campbell Jennifer , Werker Janet F. , Fyshe Alona
Published: October 2021

Infants develop foundational language skills and can understand simple words well before their first birthday. This developmental milestone has been studied primarily using looking time paradigms and Event-Related Potential (ERP) techniques, which provide evidence of word comprehension in the infant brain. While prior research validates the presence of semantic representations of words (word meaning) in infants, it does not tell us about the mental processes involved in retrieving these semantic representations or the content of the representations. To this end, we use a machine learning approach to predict the semantic representations of words using Electroencephalograms of infant brain activity. We explore semantic representations in two groups of infants (9-month-old and 12-month-old) and find significantly above chance decodability of overall word semantics, word animacy, and word phonetics. We compare decodability between the age groups and find significant differences later in the analysis window (around 700-900 ms after word onset), with higher decoding performance in 9-month-olds. Through our analysis, we also observe strong neural representations of word phonetics in the brain data for both age groups, some possibly correlated to word decoding accuracy and others not. Finally, we use the Temporal Generalization Method to show that neural representation of word semantics generalizes across the two infant age groups. Our results on word semantics, phonetics, and animacy provide insights into the evolution of neural representation of single word meaning in infants.
Cephalopod Retinal Development Shows Vertebrate-like Mechanisms of Neurogenesis
Authors: Napoli Francesca , Daly Christina M. , Neal Stephanie , McCulloch Kyle J. , Zaloga Alexandra , Liu Alicia , Koenig Kristen M.
Published: October 2021

Neurogenesis, the regulation of cellular proliferation and differentiation in the developing nervous system, is the process that underlies the diversity of size and cell type found in animal nervous systems. Our understanding of how this process has evolved is limited because of the lack of high resolution data and live-imaging methods across species. The retina is a classic model for the study of neurogenesis in vertebrates and live-imaging of the retina has shown that during development, progenitor cells are organized in a pseudostratified neuroepithelium and nuclei migrate in coordination with the cell cycle along the apicobasal axis of the cell, a process called interkinetic nuclear migration. Eventually cells delaminate and differentiate within the boundaries of the epithelium. This process has been considered unique to vertebrates and thought to be important in maintaining organization during the development of a complex nervous system. Coleoid cephalopods, including squid, cuttlefish and octopus, have the largest nervous system of any invertebrate and convergently-evolved camera-type eyes, making them a compelling comparative system to vertebrates. Here we have pioneered live-imaging techniques to show that the squid, Doryteuthis pealeii, displays cellular mechanisms during cephalopod retinal neurogenesis that are hallmarks of vertebrate processes. We find that retinal progenitor cells in the squid undergo interkinetic nuclear migration until they exit the cell cycle, we identify retinal organization corresponding to progenitor, post-mitotic and differentiated cells, and we find that Notch signaling regulates this process. With cephalopods and vertebrates having diverged 550 million years ago, these results suggest that mechanisms thought to be unique to vertebrates may be common to highly proliferative neurogenic primordia contributing to a large nervous system.
Somatic variation as an incidental finding in the pediatric next-generation sequencing era
Authors: Melas Marilena , Mathew Mariam T. , Mori Mari , Jayaraman Vijayakumar , Wilson Sarah A. , Martin Cortlandt , Jacobson-Kelly Amanda E. , Kelly Ben J. , Magrini Vincent , Mardis Elaine R. , Cottrell Catherine E. , Lee Kristy
Published: October 2021

The methodologic approach used in next-generation sequencing (NGS) affords a high depth of coverage in genomic analysis. Inherent in the nature of genomic testing, there exists potential for identifying genomic findings that are incidental or secondary to the indication for clinical testing, with the frequency dependent on the breadth of analysis and the tissue sample under study. The interpretation and management of clinically meaningful incidental genomic findings is a pressing issue particularly in the pediatric population. Our study describes a 16-mo-old male who presented with profound global delays, brain abnormality, progressive microcephaly, and growth deficiency, as well as metopic craniosynostosis. Clinical exome sequencing (ES) trio analysis revealed the presence of two variants in the proband. The first was a de novo variant in the PPP2R1A gene (c.773G > A, p.Arg258His), which is associated with autosomal dominant (AD) intellectual disability, accounting for the proband's clinical phenotype. The second was a recurrent hotspot variant in the CBL gene (c.1111T > C, p.Tyr371His), which was present at a variant allele fraction of 11%, consistent with somatic variation in the peripheral blood sample. Germline pathogenic variants in CBL are associated with AD Noonan syndrome–like disorder with or without juvenile myelomonocytic leukemia. Molecular analyses using a different tissue source, buccal epithelial cells, suggest that the CBL alteration may represent a clonal population of cells restricted to leukocytes. This report highlights the laboratory methodologic and interpretative processes and clinical considerations in the setting of acquired variation detected during clinical ES in a pediatric patient.
Abridged spectral matrix inversion: parametric fitting of X-ray fluorescence spectra following integrative data reduction
Authors: Crawford Andrew M. , Huntsman Ben , Weng Monica Y. , Ponomarenko Olena , Kiani Cheyenne D. , George Simon J. , George Graham N. , Pickering Ingrid J.
Published: October 2021

Recent improvements in both X-ray detectors and readout speeds have led to a substantial increase in the volume of X-ray fluorescence data being produced at synchrotron facilities. This in turn results in increased challenges associated with processing and fitting such data, both temporally and computationally. Herein an abridging approach is described that both reduces and partially integrates X-ray fluorescence (XRF) data sets to obtain a fivefold total improvement in processing time with negligible decrease in quality of fitting. The approach is demonstrated using linear least-squares matrix inversion on XRF data with strongly overlapping fluorescent peaks. This approach is applicable to any type of linear algebra based fitting algorithm to fit spectra containing overlapping signals wherein the spectra also contain unimportant (non-characteristic) regions which add little (or no) weight to fitted values, e.g. energy regions in XRF spectra that contain little or no peak information.
Daiquiri: a web-based user interface framework for beamline control and data acquisition
Authors: Fisher Stuart , Oscarsson Marcus , De Nolf Wout , Cotte Marine , Meyer Jens
Published: October 2021

Daiquiri is a web-based user interface (UI) framework for control system monitoring and data acquisition designed for synchrotron beamlines. It provides simple, intuitive and responsive interfaces to control and monitor hardware, launch acquisition sequences and manage associated metadata. Daiquiri concerns itself only with the UI layer; it does not provide a scan engine or controls system but can be easily integrated with existing systems.
Evaluation of protein digestibility and iodine bioavailability in raw and cooked Sargassum fusiforme (harvey) setchell using in vitro methods
Authors: Sun Nan , Tan Beibei , Sun Bolun , Zhang Jinjie , Li Chao , Yang Wenge
Published: October 2021

Purpose

Sargassum fusiforme is a popular edible seaweed in coastal cities of China that contains diverse nutrients including iodine. Cooking is an effective way to improve food safety, but it can alter both the contents of elements along with speciation and bioavailability. Three common cooking methods, the soaking, steaming and boiling, were evaluated for their effects on the protein structures, protein digestibility, iodine content and iodine bioavailability of S. fusiforme.

Design/methodology/approach

Fourier transform infrared spectroscopy was used to study the structural changes of protein, and an in vitro digestion/Caco-2 cell culture system was used to evaluate the digestibility of protein, bioaccessibility and bioavailability of iodine.

Findings

Boiling and steaming altered the protein secondary structure demonstrated by increased a-helix and random coil and decreased β-sheet, which improved the in vitro protein digestibility. Iodine content was reduced by cooking, with the highest loss observed after boiling, followed by soaking and steaming, while it was found that both bioaccessibility and cellular uptake of iodine were significantly elevated by boiling and steaming using an in vitro digestion/Caco-2 cell culture system. The presence of ascorbic acid, citric acid or tyrosine was beneficial for the iodine absorption, while oxalic acid and phytic acid hindered the iodine bioavailability.

Originality/value

The present finding suggested that cooking was conducive to the digestion and absorption of iodine in S. fusiforme. In addition, different dietary factors could have a certain impact on the absorption of iodine. Results of the study are essential for improving the application value of S. fusiforme to ensure reasonable consumption of seaweeds.
Benchmarking the assessment of barriers to the admission of management education in India during the COVID-19 pandemic
Authors: Tarei Pradeep Kumar , Kumar Santosh
Published: October 2021

Purpose

This paper proposes a decision-making framework for assessing various dimensions and barriers that have affected the admission process in management educational institutions during the ongoing pandemic. The framework considers the interrelationship between the obstacles and highlights the importance of each barrier.

Design/methodology/approach

An integrated method based on decision-making trial and evaluation laboratory and analytical network process is proposed to structure the barrier assessment framework. Results obtained from the study are validated by comparing them against the conventional analytical hierarchy process.

Findings

The results obtained from this study indicate four significant dimensions that hinder admission in Indian management institutes, namely, governmental, financial, sectoral, institutional and market. The top five barriers are demand shift towards technical (alternative) skills, acceptance of the graduated students, lack of industry–institute collaboration, lack of long-term vision and opening new Indian Institute of Technologies (IITs) and Indian Institute of Managements (IIMs).

Research limitations/implications

During this ongoing pandemic, many educational institutes have been forced to shift from the traditional classroom to a virtual teaching model. In this regard, this study helps identify and assess the barriers to admission in Indian management institutes during this epidemic and thus, contribute to the literature. The findings will assist all stakeholders and policymakers of management institutions design and develop appropriate managerial strategies. The study is conducted in the Indian management educational institute context and can be extended to technical education institutions for deeper insights.

Originality/value

The paper develops an assessment framework for analysing the barriers to admission in Indian management institutes during the ongoing COVID-19 pandemic. Research implications are discussed in the context of a developing country.
A labelling system and automation comparison index for industry 4.0 system
Authors: Kumar Shailendra , Asjad Mohammad , Suhaib Mohd.
Published: October 2021

Purpose

This paper aims to put forward a labelling system capable of reflecting the level of different Industry 4.0 (I4.0)features present in a manufacturing system and further propose a comparative index to collectively estimate and compare the system automation level.

Design/methodology/approach

Data for the empirical study were collected from interactions with the practising managers and experts. A relationship among the six I4.0 features is developed with fuzzy cognitive maps.

Findings

The paper proposed a simple and easy-to-understand labelling system for I4.0 systems, which indicates the automation level in each of six dimensions of any manufacturing system. The system is further strengthened by a proposed automation comparative index (ACI), which collectively reflects the automation level on a scale of “0” to “1”. Thus, the labelling system and parameter could help in comparing the level of automation in the manufacturing system and further decision-making.

Research limitations/implications

Only seven industrial sectors are illustrated in the paper, but the proposed concept of the classification scheme and ACI find their applicability on a large spectrum of industries; thus, the concept can be extended to other industrial sectors. Furthermore, a threshold value of ACI is a differentiator between a I4.0 and other automated systems. Both aspects have the scope of further work.

Practical implications

The way and pace by which the industrial world takes forward the concept of I4.0, soon it will need a labelling system and a parameter to assess the automation level of any automated system. The scheme assesses the automation level present in a manufacturing system. It will also estimate the level of the presence of each of all six attributes of an I4.0 system. Both labelling system and ACI will be the practical tools in the hands of the practising managers to help compare, identify the thrust areas and make decisions accordingly.

Originality/value

To the best of the authors’ knowledge, this is the first study of its kind that proposed the labelling system and automation comparison index for I4.0 systems.
Designing antifragile social-technical information systems in an era of big data
Authors: Abbas Roba , Munoz Albert
Published: October 2021

Purpose

To explore the value and the case for designing antifragile socio-technical information systems (IS) in an era of big data, moving beyond traditional notions of IS design towards systems that can leverage uncertainty for gains.

Design/methodology/approach

A design science research (DSR) approach was adopted, comprising four stages, including problem identification and solutions definition, conceptual artifact or socio-technical system design, preliminary evaluation, and communication and knowledge capture.

Findings

A conceptual socio-technical artifact that identifies antecedents to antifragile IS design. When operationalised, the antecedents may produce the desired antifragile outcome. The antecedents are categorised as value propositions, design decisions and system capabilities.

Research limitations/implications

This research is conceptual in nature, applied and evaluated in a single big data analytics case study in Facebook-Cambridge Analytica. Future research should empirically validate across a range of real-world big data contexts, beyond the presented case study.

Practical implications

Uncertainty generally results in socio-technical system failures, impacting individuals, organisations and communities. Conversely, antifragile IS can respond favourably to the shocks and stressors brought forth by periods of elevated uncertainty.

Social implications

Antifragile IS can drive socio-technical systems to respond favourably to uncertainty and stressors. Typically, these socio-technical systems are large, complex structures, with increased connectivity and the requirement to generate, process, analyse and use large datasets. When these systems fail, it affects individuals, organisations and communities.

Originality/value

Existing IS design methodologies and frameworks largely ignore antifragility as a possible designable outcome. Extant research is limited to abstract architectural design, and approaches based on the proposition of principles. This research contributes to knowledge of antifragile IS design, by deriving a conceptual artifact or socio-technical system based on antecedent-outcome relationships that leverage uncertainty towards performance gains.