bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical control of visually-guided movements in a 3D-printed robot arm
Authors: Matić Adam , Valerjev Pavle , Gomez-Marin Alex
Published: August 2021

The control architecture guiding simple movements such as reaching toward a visual target remains an open problem. The nervous system needs to integrate different sensory modalities and coordinate multiple degrees of freedom in the human arm to achieve that goal. The challenge increases due to noise and transport delays in neural signals, nonlinear and fatigable muscles as actuators, and unpredictable environmental disturbances. Here we examined the capabilities of a previously proposed hierarchical feedback control model (Powers 1999, 2008), so far only testedin silico. We built a robot arm system with four degrees of freedom, including a visual system for locating the planar position of the hand, joint angle proprioception, and pressure sensing in one point of contact. We subjected the robot to various human-inspired reaching and tracking tasks and found features of biological movement, such as isochrony and bell-shaped velocity profiles in straight-line movements, and the speed-curvature power law in curved movements. These behavioral properties emerge without trajectory planning or explicit optimization algorithms. We then applied static structural perturbations to the robot: we blocked the wrist joint, tilted the writing surface, extended the hand with a tool, and rotated the visual system. For all of them, we found that the armin machinaadapts its behavior without being reprogrammed. In sum, while limited in speed and precision (by the nature of the do-it-yourself inexpensive components we used to build the robot from scratch), when faced with the noise, delays, nonlinearities, and unpredictable disturbances of the real world, the embodied control architecture shown here balances biological realism with design simplicity.
Characterization of the composition and functioning of the Crumbs complex in C. elegans
Authors: Castiglioni Victoria G , Ramalho João J , Kroll Jason , Stucchi Riccardo , van Beuzekom Hanna , Schmidt Ruben , Altelaar Maarten , Boxem Mike
Published: August 2021

The apical domain of epithelial cells can acquire a diverse array of morphologies and functions, which is critical for the function of epithelial tissues. The Crumbs proteins are evolutionary conserved transmembrane proteins with essential roles in promoting apical domain formation in epithelial cells. The short intracellular tail of Crumbs proteins interacts with a variety of proteins, including the scaffolding protein Pals1 (protein associated with LIN7, Stardust in Drosophila). Pals1 in turn binds to a second scaffolding protein termed PATJ (Pals1-associated tight junction protein), to form the core Crumbs/Pals1/PATJ Crumbs complex. While essential roles in epithelial organization have been shown for Crumbs proteins in Drosophila and mammalian systems, the three Caenorhabditis elegans crumbs genes are dispensable for epithelial polarization and animal development. Moreover, the presence and functioning of orthologs of Pals1 and PATJ has not been investigated. Here, we identify MAGU-2 and MPZ-1 as the C. elegans orthologs of Pals1 and PATJ, respectively. We show that MAGU-2 interacts with all three Crumbs proteins as well as MPZ-1, and localizes to the apical membrane domain in a Crumbs-dependent fashion. Similar to crumbs mutants, a magu-2 null mutant shows no developmental or epithelial polarity defects. Finally, we show that overexpression of the Crumbs proteins EAT-20 or CRB-3 in the C. elegans intestine can lead to apical membrane expansion. Our results shed light into the composition of the C. elegans Crumbs complex and indicate that the role of Crumbs proteins in promoting apical domain formation is conserved.
Mucin induces CRISPR-Cas defence in an opportunistic pathogen
Authors: Almeida Gabriel MF , Hoikkala Ville , Ravantti Janne , Rantanen Noora , Sundberg Lotta-Riina
Published: August 2021

Parasitism by bacteriophages has led to the evolution of a variety of defense mechanisms in their host bacteria. However, it is unclear what factors lead to specific defenses being deployed upon phage infection. To explore this question, we exposed the bacterial fish pathogenFlavobacterium columnareto its virulent phage V156 in the presence of a eukaryotic host signal (mucin). All tested conditions led to some level of innate immunity, but the presence of mucin led to a dramatic increase in CRISPR spacer acquisition, especially in low nutrient conditions where over 60% of colonies had obtained at least one new spacer. Additionally, we show that the presence of a competitor bacterium further increases CRISPR spacer acquisition inF. columnare. These results suggest that ecological factors are important in determining defense strategies against phages, and that the concentration of phages on metazoan surfaces may select for the diversification of bacterial immune systems.
Mammal virus diversity estimates are unstable due to accelerating discovery effort
Authors: Gibb Rory , Albery Gregory F. , Mollentze Nardus , Eskew Evan A. , Brierley Liam , Ryan Sadie J. , Seifert Stephanie N. , Carlson Colin J.
Published: August 2021

Host-virus association data form the backbone of research into eco-evolutionary drivers of viral diversity and host-level zoonotic risk. However, knowledge of the wildlife virome is inherently constrained by historical discovery effort, and there are concerns that the reliability of ecological inference from host-virus data may be undermined by taxonomic and geographical sampling biases. Here, we evaluate whether current estimates of host-level viral diversity in wild mammals are stable enough to be considered biologically meaningful, by analysing a comprehensive dataset of discovery dates of 6,571 unique mammal host-virus associations between 1930 and 2018. We show that virus discovery rates in mammal hosts are still either constant or accelerating, with little evidence of declines towards viral richness asymptotes in even highly-sampled hosts. Consequently, inference of relative viral richness across host species has been unstable over time, particularly in bats, where intensified surveillance since the early 2000s caused a rapid rearrangement of species’ ranked viral richness. Our results show that comparative inference of host-level virus diversity across mammals is highly sensitive to even short-term changes in sampling effort. We advise caution to avoid overinterpreting patterns in current data, since our findings suggest that an analysis conducted today could feasibly draw quite different conclusions than one conducted only a decade ago.
A novel approach to evaluate alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy
Authors: Martinez-Valbuena Ivan , Visanji Naomi P. , Kim Ain , Lau Heather H. C. , So Raphaella W. L. , Alshimemeri Sohaila , Gao Andrew , Seidman Michael , Luquin Maria R. , Watts Joel C. , Lang Anthony E. , Kovacs Gabor G.
Published: August 2021

Severalin vitroandin vivofindings have consistently shown that α-synuclein derived from multiple system atrophy (MSA) subjects has more seeding capacity than Parkinson’s disease-derived α-synuclein. However, reliable detection of α-synuclein derived from MSA using seeded amplification assays, such as the Real-Time Quaking-induced Conversion, has remained challenging. Here we demonstrate that the interaction of the Thioflavin T dye with α-synuclein from MSA and Parkinson’s disease patients can be modulated by the type of salt, pH, and ionic strength used to generate strain-specific reaction buffers. Employing this novel approach, we have generated a streamlined Real-Time Quaking-induced Conversion assay capable of categorizing MSA brains according to their α-synuclein seeding behavior, and to unravel a previously unrecognized heterogeneity in seeding activity between different brain regions of a given individual that goes beyond immunohistochemical observations and provide a framework for future molecular subtyping of MSA.
Reservoir host studies of Lloviu virus: first isolation, sequencing and serology in Schreiber’s bats in Europe
Authors: Kemenesi Gábor , Tóth Gábor Endre , Mayora-Neto Martin , Scott Simon , Temperton Nigel , Wright Edward , Mühlberger Elke , Hume Adam J. , Zana Brigitta , Boldogh Sándor András , Görföl Tamás , Estók Péter , Lanszki Zsófia , Somogyi Balázs A. , Nagy Ágnes , Pereszlényi Csaba István , Dudás Gábor , Földes Fanni , Kurucz Kornélia , Madai Mónika , Zeghbib Safia , Maes Piet , Vanmechelen Bert , Jakab Ferenc
Published: August 2021

Introductory

Filoviruses are prime examples of emerging human pathogens that are transmitted to humans by zoonotic spillover events. Since their initial discovery, filovirus outbreaks have occured with increasing frequency and intensity. There is an urgent need to better understand their enzootic ecology and pathogenic potential, given recent zoonotic virus spillover events including the 2013-2016 West African Ebola virus (EBOV) epidemic. Several novel filoviruses have been discovered with a markedly wider geographic distribution than previously described. One of these novel filoviruses, Lloviu virus (LLOV), was first identified in 2002 in Schreiber’s bats (Miniopterus schreibersii) in Spain, Portugal, and southern France. Subsequently, in 2016, LLOV was detected during the passive monitoring of bats in Hungary.

Here we report the first isolation of infectious Lloviu virus; from the blood of an asymptomatic Schreiber’s bat, subsequently cultivated in the Miniopterus sp. kidney cell line SuBK12-08. We also show that LLOV is able to infect monkey and human cells, suggesting that LLOV might have spillover potential. We performed a multi-year surveillance of LLOV and detected LLOV RNA in both deceased and asymptomatic live animals as well as in coupled ectoparasites from the families Nycteribiidae and Ixodidae. We present data on the natural infection and seropositivity of Schreiber’s bats and provide novel LLOV genomic sequence information from a bat host and an arthropod parasite. Our data support the role of bats, specificallyMiniopterus schreibersiias natural reservoirs for the LLOV filovirus in Europe. We also suggest that bat-associated parasites might play a role in the natural ecology of filoviruses in temperate climate regions compared to filoviruses in the tropics. These results raise the possibility of cross-species transmission events via bat-human interactions.
Generation of iPSCs from endangered Grevy’s zebra and comparative transcriptomic analysis of mammalian PSCs
Authors: Endo Yoshinori , Kamei Ken-ichiro , Hasegawa Koichi , Okita Keisuke , Ito Hideyuki , Terada Shiho , Inoue-Murayama Miho
Published: August 2021

Induced pluripotent stem cells (iPSCs) can provide a biological resource for functional and conservation research in various species. This expectation has led to generation of iPSCs from various species, including those identified as endangered species. However, the understanding of species variation in mammalian iPSCs is largely unknown. Here, to gain insight into the species variation in iPSCs, we the first generated iPSCs from the endangered species Grevy’s zebra (Equus grevyi; gz-iPSCs) for the first time in the world. We isolated primary fibroblasts cell from an individual that had died of natural causes at a zoo and reprogrammed the fibroblasts into iPSCs. We confirmed their pluripotency and differentiation potential and performed RNA sequencing analysis. The gz-iPSC transcriptome showed that the generated gz-iPSCs robustly expressed genes associated with pluripotency and reprogramming processes, including epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions. Comparative transcriptomics with other species revealed patterns of gene expression among mammalian PSCs and detected evolutionary conservation of pluripotency-associated genes and the plausible importance of the translation process. This study provides new insights into the evolution of mammalian PSCs, and the species conservation and variation of PSCs will advance our understanding of the early development of mammals.
RNA X-ray footprinting reveals the consequences of anin vivoacquired determinant of viral infectivity
Authors: Chandler-Bostock Rebecca , Bingham Richard J. , Clark Sam , Scott Andrew J. P. , Wroblewski Emma , Barker Amy , White Simon J. , Dykeman Eric C. , Mata Carlos P. , Bohon Jen , Farquhar Erik , Twarock Reidun , Stockley Peter G.
Published: August 2021

The secondary structures of the bacteriophage MS2 ssRNA genome, frozen in defined states, were determined with minimal perturbation using constraints from X-ray synchrotron footprinting (XRF). The footprints of the gRNA in the virion and as transcript are consistent with single, dominant but distinct conformations, and reveal the presence of multiple Packaging Signals potentially involved in assembly regulation that have not been detected by other techniques. XRF also reveals the dramatic effect of the unique Maturation Protein (MP) on both the capsid lattice, and the gRNA conformation inside the phage compared with a virus-like-particle composed only of coat protein subunits. Aspects of genome organisation in the phage, their impacts on the capsid shell, and the distortion of lattice geometry by MP, are hallmarks of molecular frustration. Phage assembly therefore appears to prepare the particle for the next step of the infectious cycle.
Lung injury induces alveolar type 2 cell hypertrophy and polyploidy with implications for repair and regeneration
Authors: Weng Anthea , Maciel-Herrerias Mariana , Watanabe Satoshi , Welch Lynn , Flozak Annette S. , Grant Rogan , Aillon Raul Piseaux , Dada Laura , Han Seung Hye , Hinchcliff Monique , Misharin Alexander , Budinger GR Scott , Gottardi Cara J.
Published: August 2021

Epithelial polyploidization post-injury is a conserved phenomenon, recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces AT2 cell hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 trans-differentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response (ISR) using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. As AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the ISR.
Structure-function analysis of distant diphtheria toxin homologs reveals insights into host adaptation
Authors: Sugiman-Marangos Seiji N. , Gill Shivneet K. , Mansfield Michael J. , Orrell Kathleen E. , Doxey Andrew C. , Melnyk Roman A.
Published: August 2021

Diphtheria toxin (DT) is the archetype of bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial toxins, the origins and molecular evolution of DT host specialization remain unknown. Here, we determined high-resolution structures of two recently discovered distant homologs of DT. These DT-like proteins from non-human associatedStreptomyces albireticuli(17% identity to DT) andSeinonella peptonophila(20% identity to DT) display remarkable structural similarity to DT enabling a comparative investigation into DT’s unique toxicity toward mammalian cells. We find that the individual domains of DT-like toxins retain two critical features of DT’s activity: full catalytic function and ability to translocate across mammalian cell membranes. However, we show that receptor-binding, pH-dependent pore-formation and proteolytic release of the cytotoxic enzyme into the cytosol are not optimized for human cell physiology and thus unable to efficiently deliver the cytotoxic cargo into human hosts. Our work provides structural insights into DT’s evolutionary history, and implies key transitions required for the emergence of human-specificity of a major bacterial exotoxin with an important history in human disease.
TSC2-extracellular matrix crosstalk controls pulmonary vascular proliferation and pulmonary hypertension
Authors: Shen Yuanjun , Goncharov Dmitry A. , Pena Andressa , Baust Jeffery , Barragan Andres Chavez , Ray Arnab , Rode Analise , Bachman Timothy N. , Chang Baojun , Rojas Mauricio , DeLisser Horace , Mora Ana L. , Kudryashova Tatiana V. , Goncharova Elena. A.
Published: August 2021

Increased proliferation and survival of resident cells in small pulmonary arteries (PA) are important drivers of pulmonary hypertension (PH). Tuberous sclerosis complex 2 (TSC2) is a negative regulator of mTOR complex 1 and cell growth. Here we show that TSC2 is deficient in small remodeled PA/PA vascular smooth muscle cells (PAVSMC) from human PAH and experimental PH lungs. TSC2 deficiency was reproducedin vitroby maintaining PAVSMC on pathologically stiff substrates and was required for stiffness-induced proliferation, accumulation of transcriptional co-activators YAP/TAZ and up-regulation of mTOR. Depletion of TSC2 reproduced PH featuresin vitroin human PAVSMC andin vivoin SM22-Tsc2+/− mice. TSC2 loss in PAVSMC was supported by YAP and led to the up-regulation of YAP/TAZ and mTOR via modulating the extracellular matrix (ECM) composition. ECM, produced by TSC2-deficient PAVSMC, promoted growth of non-diseased PA adventitial fibroblasts and PAVSMC, which, in turn, was prevented by α5β1 integrin receptor antagonist ATN161.In vitro, molecular and pharmacological (SRT2104) restoration of TSC2 down-regulated YAP/TAZ, mTOR, and ECM production, inhibited proliferation and induced apoptosis in human PAH PAVSMC.In vivo, orally administrated SRT2104 restored TSC2, resolved pulmonary vascular remodeling, PH, and improved right heart in two rodent models of PH. Thus, PAVSMC TSC2 is a critical integrator of ECM composition and stiffness with pro-proliferative signaling and PH, and the restoration of functional TSC2 could be an attractive therapeutic option to treat PH.

One Sentence Summary

TSC2 acts as mechanosensor and mechanotransducer, integrating ECM composition and stiffness with pro-proliferative signaling in pulmonary vasculature; its deficiency in PA vascular smooth muscle cells results in ECM remodeling, hyper-proliferation and pulmonary hypertension, which could be reversed by pharmacological restoration of functional TSC2.
Stress-dependent inhibition of cell polarity through unbalancing the GEF/GAP regulation of Cdc42
Authors: Salat-Canela Clàudia , Carmona Mercè , Martín-García Rebeca , Pérez Pilar , Ayté José , Hidalgo Elena
Published: August 2021

Cdc42 rules cell polarity and growth in fission yeast. It is negatively and positively regulated by GTPase-activating proteins (GAPs) and by Guanine nucleotide Exchange factors (GEFs), respectively. Active Cdc42-GTP localizes to the poles, where it associates with numerous proteins constituting the polarity module. However, little is known about its down-regulation. We describe here that oxidative stress causes Sty1 kinase-dependent Cdc42 inactivation at cell poles. Both the amount of active Cdc42 at poles and cell length inversely correlate with Sty1 activity, explaining the elongated morphology of Δsty1 cells. We have created stress-blinded cell poles by either eliminating two Cdc42 GAPs or through the constitutive tethering of a GEF to the cell tips, and biochemically demonstrate that Rga3 is a direct substrate of Sty1. We propose that stress-activated Sty1 promotes GTP hydrolysis and prevents GEF activity at the cell tips, thus leading to the inhibition of Cdc42 and polarized growth cessation.
Evolutionary divergence of anaphase spindle mechanics in nematode embryos constrained by antagonistic pulling and viscous forces
Authors: Khatri Dhruv , Brugière Thibault , Athale Chaitanya A. , Delattre Marie
Published: August 2021

Cells are the basic unit of biological organization, and their division is remarkably conserved across phyla. However from an evolutionary perspective, it remains unclear how much cellular parameters can diverge, without altering the basic function they sustain. We address the mechanics of asymmetric mitotic spindle positioning during the first embryonic division of six nematode species. We propose a viscoelastic model of spindle positioning and mobility that can provide a physical explanation of why in C. elegans it undergoes oscillations during elongation, whereas most others lack oscillations. To test this model, we measured the pulling forces and opposing cytoplasmic drag by a combination of laser ablation of the anaphase spindle and tracking of intracellular granules. While centrosomes of all species recoil on spindle cutting, quantitative differences correlate with the cytoplasmic viscosity. In fact, increased viscosity correlates with decreased oscillation speeds of intact spindles across species. However, the absence of oscillations despite low viscosity in some species, can only be explained by smaller pulling forces. Consequently, we find that spindle mobility across the species analyzed here is characterized by a tradeoff between cytoplasmic viscosity and pulling forces. Our work provides a framework for understanding mechanical constraints on evolutionary diversification of spindle mobility.
Unusually slow spike frequency adaptation in deep cerebellar nuclei neurons preserves linear transformations on the sub-second time scale
Authors: Khan Mehak M. , Chen Christopher H. , Regehr Wade G.
Published: August 2021

Purkinje cells (PCs) are spontaneously active neurons of the cerebellar cortex that inhibit glutamatergic projection neurons within the deep cerebellar nuclei (DCN) that in turn provide the primary cerebellar output. Brief reductions in PC firing rapidly increase DCN neuron firing. However, prolonged reductions in PC inhibition, as seen in some disease states, certain types of transgenic mice, and in acute slices of the cerebellum, do not evoke large sustained increases in DCN firing. Here we test whether there is a mechanism of spike-frequency adaptation in DCN neurons that could account for these properties. We find that prolonged optogenetic suppression of PC synapsesin vivotransiently elevates PC firing that strongly adapts within ten seconds. We perform current-clamp recordings at near physiological temperature in acute brain slices to examine how DCN neurons respond to prolonged depolarizations. Adaptation in DCN neurons is exceptionally slow and bidirectional. A depolarizing current step evokes large initial increases in firing that decay to less than 20% of the initial increase within approximately ten seconds. Such slow adaptation could allow DCN neurons to adapt to prolonged changes in PC firing while maintaining their linear firing frequency-current relationship on subsecond time scales.
Neural stem cell expressed vascular endothelial growth factor maintains the neurogenic vascular niche of the adult mouse hippocampus
Authors: Dause Tyler J. , Denninger Jiyeon K. , Osap Robert , Walters Ashley E. , Rieskamp Joshua D. , Kuwahara Akela A. , Kirby Elizabeth D.
Published: August 2021

The vasculature is a key component of adult brain neural stem cell (NSC) niches. In the adult mammalian hippocampus, NSCs reside in close contact with a dense capillary network. How this niche is maintained is unclear. We recently found that adult hippocampal NSCs express vascular endothelial growth factor (VEGF), a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that NSC-specific VEGF loss led to dissociation of NSCs from local vasculature but surprisingly found no changes in vascular density. Instead, we found that NSC-derived VEGF supports the motility of NSCs themselves via a cell internal signaling loop. We further found that this internal autocrine loop also independently maintained NSC quiescence cell autonomously. Combined, our findings suggest that NSCs maintain their populations via 2 mechanisms that are dependent on cell internal VEGF signaling: self-stimulated motility towards vasculature and cell autonomous maintenance of quiescence programs.
A systematic data-driven approach to analyze sensor-level EEG connectivity: Identifying robust phase-synchronized network components using surface Laplacian with spectral-spatial PCA
Authors: Smith Ezra E. , Bel-Bahar Tarik S. , Kayser Jürgen
Published: August 2021

Although conventional averaging across predefined frequency bands reduces the complexity of EEG functional connectivity (FC), it obscures the identification of resting-state brain networks (RSN) and impedes accurate estimation of FC reliability. Extending prior work, we combined scalp current source density (CSD; spherical spline surface Laplacian) and spectral-spatial PCA to identify FC components. Phase-based FC was estimated via debiased weighted phase-locking index from CSD-transformed resting EEGs (71 sensors, 8 min, eyes open/closed, 35 healthy adults, 1-week retest). Spectral PCA extracted 6 robust alpha and theta factors (86.6% variance). Subsequent spatial PCA for each spectral factor revealed seven robust regionally-focused (posterior, central, frontal) and long-range (posterior-anterior) alpha components (peaks at 8, 10 and 13 Hz) and a midfrontal theta (6 Hz) component, accounting for 37.0% of FC variance. These spatial FC components were consistent with well-known networks (e.g., default mode, visual, sensorimotor), and four were sensitive to eyes open/closed conditions. Most FC components had good-to-excellent internal consistency (odd/even epochs, eyes open/closed) and test-retest reliability (ICCs ≥ .8). Moreover, the FC component structure was generally present in subsamples (session × odd/even epoch, or smaller subgroups [n = 7-10]), as indicated by similarity of factor loadings across PCA solutions. Apart from systematically reducing FC dimensionality, our approach avoids arbitrary thresholds and allows quantification of meaningful and reliable network components that may prove to be of high relevance for basic and clinical research applications.
Long-term Transverse Imaging of the Hippocampus with Glass Microperiscopes
Authors: Redman William T , Wolcott Nora S , Montelisciani Luca , Luna Gabriel , Marks Tyler D , Sit Kevin K , Yu Che-Hang , Smith Spencer L , Goard Michael J
Published: August 2021

The hippocampus consists of a stereotyped neuronal circuit repeated along the septal-temporal axis. This transverse circuit contains distinct subfields with stereotyped connectivity that support crucial cognitive processes, including episodic and spatial memory. However, comprehensive measurements across the transverse hippocampal circuit in vivo are intractable with existing techniques. Here, we developed an approach for two-photon imaging of the transverse hippocampal plane in awake mice via implanted glass microperiscopes, allowing optical access to the major hippocampal subfields and to the dendritic arbor of pyramidal neurons. Using this approach, we tracked dendritic morphological dynamics on CA1 apical dendrites and characterized spine turnover. We then used calcium imaging to quantify the prevalence of place and speed cells across subfields. Finally, we measured the anatomical distribution of spatial information, finding a non-uniform distribution of spatial selectivity along the DG-to-CA1 axis. This approach extends the existing toolbox for structural and functional measurements of hippocampal circuitry.
LACK OF EVIDENCE FOR A VIABLE MICROBIOTA IN MURINE AMNIOTIC FLUID
Authors: Winters Andrew D. , Romero Roberto , Greenberg Jonathan M. , Galaz Jose , Shaffer Zachary , Garcia-Flores Valeria , Kracht David J. , Gomez-Lopez Nardhy , Theis Kevin R.
Published: August 2021

The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of the role of intra-amniotic microbes in fetal development and pregnancy outcomes. In this study, we determined whether the amniotic fluid of mice harbors a microbiota in late gestation. Bacterial profiles of amniotic fluids located proximally or distally to the cervix were characterized through quantitative real-time PCR, 16S rRNA gene sequencing, and culture (N = 21 mice). These profiles were compared to those of technical controls for background DNA contamination. The load of 16S rDNA in the amniotic fluid exceeded that in controls. Additionally, the 16S rDNA profiles of the amniotic fluid differed from those of controls, withCorynebacterium tuberculostearicumbeing differentially more abundant in amniotic fluid profiles; however, this bacterium was not cultured. Of the 42 total bacterial cultures of amniotic fluids, only one yielded bacterial growth –Lactobacillus murinus. The 16S rRNA gene of this common murine-associated bacterium was not detected in any amniotic fluid sample, suggesting it did not originate from the amniotic fluid. No differences in 16S rDNA load, 16S rDNA profile, or bacterial culture were observed between amniotic fluids located proximal and distal to the cervix. Collectively, these data show that, although there is a modest DNA signal of bacteria in murine amniotic fluid, there is no evidence that this signal represents a viable microbiota. These findings refute the proposed role of amniotic fluid as a source of microorganisms forin uterocolonization.

IMPORTANCE

The prevailing paradigm in obstetrics has been the sterile womb hypothesis, which posits that fetuses are first colonized by microorganisms during labor and/or the vaginal delivery process. However, it has been suggested that fetuses are consistently colonizedin utero. One proposed source of colonizers is the amniotic fluid surrounding the fetus. This concept has been derived primarily from investigations that relied on DNA sequencing. Due to the low microbial biomass of amniotic fluid, such studies are susceptible to influences of background DNA contamination. Additionally, even if there is a microbial DNA signature in amniotic fluid, this is not necessarily reflective of a resident microbiota that could colonize the mammalian fetus. In the current study, using multiple microbiologic approaches and incorporating technical controls for DNA contamination, we show that, although there is a low abundance bacterial DNA signal in amniotic fluid, this does not translate to the presence of viable bacteria.
Severity of respiratory failure and computed chest tomography in acute COVID-19 correlates with pulmonary function and respiratory symptoms after infection with SARS-CoV-2: an observational longitudinal study over 12 months
Authors: Steinbeis Fridolin , Thibeault Charlotte , Doellinger Felix , Ring Raphaela Maria , Mittermaier Mirja , Ruwwe-Glösenkamp Christoph , Alius Florian , Knape Philipp , Meyer Hans-Jakob , Lippert Lena Johanna , Helbig Elisa Theresa , Grund Daniel , Temmesfeld-Wollbrück Bettina , Suttorp Norbert , Sander Leif Erik , Kurth Florian , Penzkofer Tobias , Witzenrath Martin , Zoller Thomas
Published: August 2021

Background

Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse.

Research question

With this study, we aim to investigate pulmonary outcome following SARS-CoV-2 infection including pulmonary function, computed chest tomography, respiratory symptoms and quality of life over 12 months.

Study design and Methods

180 patients after acute COVID-19 were enrolled into a single-centre, prospective observational study and examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate objective and subjective respiratory limitations. Patients were stratified according to acute COVID-19 disease severity.

Results

Of 180 patients enrolled, 42/180 were not hospitalized during acute SARS-CoV-2 infection, 29/180 were hospitalized without need for oxygen, 43/180 with need for low-flow and 24/180 with high-flow oxygen, 26/180 required invasive mechanical ventilation and 16/180 were treated with ECMO. After acute COVID-19, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity after the acute phase and improved over 12 months except for those requiring ECMO treatment. Patients with milder disease showed a predominant reduction of ventilated area instead of simple restriction. The CT score of lung involvement in the acute phase increased significantly with COVID-19 severity and was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with mild initially disease.

Interpretation

Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection. Patients with mild vs. severe disease show different patterns of lung involvement and symptom resolution.

Clinical Trial Registration

The study is registered at the German registry for clinical studies (DRKS00021688)
Stress-induced collective behavior leads to the formation of multicellular structures and the survival of the unicellular alga Chlamydomonas
Authors: de Carpentier Félix , Maes Alexandre , Marchand Christophe H. , Chung Céline , Durand Cyrielle , Crozet Pierre , Lemaire Stéphane D. , Danon Antoine
Published: August 2021

Depending on their nature, living organisms use various strategies to adapt to environmental stress conditions. Multicellular organisms implement a set of reactions involving signaling and cooperation between different types of cells. Unicellular organisms on the other hand must activate defense systems, which involve collective behaviors between individual organisms. In the unicellular model algaChlamydomonas reinhardtii, the existence and the function of collective behavior mechanisms in response to stress remain largely unknown. Here we report the discovery of a mechanism of abiotic stress response that Chlamydomonas can trigger to form large multicellular structures that can comprise several thousand cells. We show that these aggregates constitute an effective bulwark within which the cells are efficiently protected from the toxic environment. We have generated the first family of mutants that aggregate spontaneously, thesocializermutants (saz), of which we describe here in detailsaz1. We took advantage of thesazmutants to implement a large scale multiomics approach that allowed us to show that aggregation is not the result of passive agglutination, but rather genetic reprogramming and substantial modification of the secretome. The reverse genetic analysis we conducted on some of the most promising candidates allowed us to identify the first positive and negative regulators of aggregation and to make hypotheses on how this process is controlled in Chlamydomonas.
Dynamics of cortical contrast adaptation predict perception of signals in noise
Authors: Angeloni Christopher F. , Młynarski Wiktor , Piasini Eugenio , Williams Aaron M. , Wood Katherine C. , Garami Linda , Hermundstad Ann M. , Geffen Maria N.
Published: August 2021

Neurons throughout the sensory pathway adapt their responses depending on the statistical structure of the sensory environment. Contrast gain control is a form of adaptation in the auditory cortex, but it is unclear whether the dynamics of gain control reflect efficient adaptation, and whether they shape behavioral perception. Here, we trained mice to detect a target presented in background noise shortly after a change in the contrast of the background. The observed changes in cortical gain and behavioral detection followed the dynamics of a normative model of efficient contrast gain control; specifically, target detection and sensitivity improved slowly in low contrast, but degraded rapidly in high contrast. Auditory cortex was required for this task, and cortical responses were not only similarly affected by contrast but predicted variability in behavioral performance. Combined, our results demonstrate that dynamic gain adaptation supports efficient coding in auditory cortex and predicts the perception of sounds in noise.
Value capture in open innovation markets: the role of patent rights for innovation appropriation
Authors: Holgersson Marcus , Granstrand Ove
Published: August 2021

Purpose

The role of patents for appropriating (capturing) value from innovation investments has for decades been of major interest to both practitioners and academics in innovation management. Many studies have implicitly assumed that firms appropriate value through in-house creation and marketing of innovative products and services, and that the main function of patents is to protect the exclusive sales in product and service markets. We challenge this assumption in light of the variety of business models, strategies and markets now being available, including different organizational and market forms of open innovation.

Design/methodology/approach

A conceptual framework and typology of open innovation markets is developed, and the role of patents for appropriation is investigated in these markets among 172 Swedish technology-based firms.

Findings

The results show that the importance of patents has a skewed distribution with some firms rating patents very important and with a fat tail of firms rating patents less important. Most importantly, the results indicate that patents are enabling exchange and technology trade in various types of open innovation markets rather than only supporting vertically integrated business models. Thus patents were found to help rather than hinder the use of open innovation markets.

Originality/value

The paper makes two main contributions. First a theoretical reinterpretation of open innovation with a conceptualization of open innovation markets for appropriation of innovation values. Second an empirical illustration of new roles of patents for appropriating innovation values in these markets. The paper in addition illustrates the use of a counterfactual approach to questionnaire surveys, as well as the complementarities between patents and other means of appropriation.
Collecting and evaluating large volumes of bibliographic metadata aggregated in the WorldCat database: a proposed methodology to overcome challenges
Authors: Zavalin Vyacheslav I. , Miksa Shawne D.
Published: August 2021

Purpose

This paper aims to discuss the challenges encountered in collecting, cleaning and analyzing the large data set of bibliographic metadata records in machine-readable cataloging [MARC 21] format. Possible solutions are presented.

Design/methodology/approach

This mixed method study relied on content analysis and social network analysis. The study examined subject representation in MARC 21 metadata records created in 2020 in WorldCat – the largest international database of “big smart data.” The methodological challenges that were encountered and solutions are examined.

Findings

In this general review paper with a focus on methodological issues, the discussion of challenges is followed by a discussion of solutions developed and tested as part of this study. Data collection, processing, analysis and visualization are addressed separately. Lessons learned and conclusions related to challenges and solutions for the design of a large-scale study evaluating MARC 21 bibliographic metadata from WorldCat are given. Overall recommendations for the design and implementation of future research are suggested.

Originality/value

There are no previous publications that address the challenges and solutions of data collection and analysis of WorldCat’s “big smart data” in the form of MARC 21 data. This is the first study to use a large data set to systematically examine MARC 21 library metadata records created after the most recent addition of new fields and subfields to MARC 21 Bibliographic Format standard in 2019 based on resource description and access rules. It is also the first to focus its analyzes on the networks formed by subject terms shared by MARC 21 bibliographic records in a data set extracted from a heterogeneous centralized database WorldCat.
Reflections on writing and teaching: a study of five writing contest winners
Authors: Williams Wendy R.
Published: August 2021

Purpose

English teachers who write have valuable expertise that can benefit students. Although there is a fair amount of research on teacher-writers, little is known about teachers’ writing lives outside of educational or professional contexts. This paper aims to investigate the writing lives and teaching beliefs of five writing contest winners.

Design/methodology/approach

This qualitative study, which was guided by sociocultural theory and concepts such as literacy sponsorship, involved individual semi-structured interviews, questionnaires and writing and teaching artifacts.

Findings

Data analysis resulted in several themes describing participants’ writing lives: Writing Experiences, Writing Practices and Writing Attitudes. In addition, several themes emerged describing their teaching beliefs: Writing Assignments/Tools, Modeling and Credibility/Empathy/Vulnerability. Overlaps exist in the descriptions of their writing and teaching lives.

Practical implications

Teachers’ writing lives are valuable resources for instruction. It is recommended that teachers have opportunities to reflect on who they are as writers and what has shaped them. Teachers also need new experiences to expand their writing practices and strengthen their writing identities alongside fellow writers. More must be done to understand, nurture and sustain teachers’ writing.

Originality/value

This research expands the conversation on teachers as writers by involving writing contest winners, focusing on their writing lives and noticing how their writing experiences, practices and attitudes inform their teaching. This study suggests several ways to move forward in supporting teachers as writers, keeping in mind the social aspects of learning.
Tackling self-employment in the informal sector in Europe: evaluating trust-building strategies
Authors: Williams Colin , Windebank Jan
Published: August 2021

Purpose

The aim of this paper is to evaluate contrasting ways of tackling self-employment in the informal sector. Conventionally, the participation of the self-employed in the informal sector has been viewed as a rational economic decision taken when the expected benefits outweigh the costs, and thus enforcement authorities have sought to change the benefit-to-cost ratio by increasing the punishments and chances of being caught. Recently, however, neo-institutional theory has viewed such endeavor as a product of a lack of vertical trust (in government) and horizontal trust (in others) and pursued trust-building strategies to nurture voluntary compliance.

Design/methodology/approach

To evaluate these contrasting policy approaches, data are reported from special Eurobarometer survey 92.1 conducted in 2019 across 28 European countries (the 27 member states of the European Union and the United Kingdom) involving over 27,565 interviews.

Findings

Using probit regression analysis, the finding is that the likelihood of participation in informal self-employment is not associated with the level of expected punishments and chances of being caught, but is significantly associated with the level of vertical and horizontal trust, with a greater likelihood of participation in informal self-employment when there is lower vertical and horizontal trust.

Practical implications

The outcome is a call for state authorities to shift away from the use of repressive policy measures that increase the penalties and chances of being caught and toward trust-building strategies to nurture voluntary compliance. How this can be achieved is explored.

Originality/value

Evidence is provided to justify a shift toward seeking trust-building strategies by state authorities to engender voluntary compliance among the self-employed operating in the informal sector in Europe.
How IT integration and relational ties affect innovation performance: considering the moderating roles of relationship duration and institutional distance
Authors: Wei Shaobo , Liu Hua
Published: August 2021

Purpose

This study aims to investigate how information technology (IT) integration and relational ties between a firm and its supplier influence its innovation performance and how such relationships are moderated by relationship duration and institutional distance between the firm and its supplier.

Design/methodology/approach

Based on 153 matched-pair surveys of firms in China, the authors used regression analyses to test their hypotheses.

Findings

The authors find that IT integration and relational ties with the supplier significantly improve the firm’s innovation performance. Further, the authors find that relationship duration negatively moderates the impact of relational ties on innovation performance. Institutional distance negatively moderates the impact of IT integration, yet positively moderates the impact of relational ties on innovation performance.

Originality/value

This study provides a more nuanced insight into relational and institutional boundary conditions under which IT integration and relational ties affect innovation performance.
Examining the impact of strategic supplier partnership, customer relationship and supply chain responsiveness on operational performance: the moderating effect of demand uncertainty
Authors: Nenavani Jitendra , Jain Rajesh K.
Published: August 2021

Purpose

The purpose of this paper is to examine the impact of strategic supplier partnership and customer relationship on supply chain responsiveness and then to analyse the influence of supply chain responsiveness on operational performance in the manufacturing industry in India. In addition to that, this study also investigates the moderating effects of demand uncertainty on the relationship between strategic supplier partnership–supply chain responsiveness and customer relationship–supply chain responsiveness.

Design/methodology/approach

A structured self-administered questionnaire was developed to collect data from manufacturing companies in India. This study performed the structural equation modelling and moderated regression for testing the hypotheses after ensuring the validity and reliability of identified constructs.

Findings

Strategic supplier partnership and customer relationship positively influence supply chain responsiveness, and supply chain responsiveness also positively impacts operational performance. In addition to that, demand uncertainty negatively moderates the relationship between strategic supplier partnership and supply chain responsiveness. However, demand uncertainty does not significantly affect the relationship between customer relationship and supply chain responsiveness.

Originality/value

Strategic supplier partnership and customer relationship are firstly investigated as antecedents of supply chain responsiveness. To the best of the author’s knowledge, this study is one of the first to examine the moderating effect of demand uncertainty on the relationship between supply chain practices (strategic supplier partnership and customer relationship) and supply chain responsiveness.