bluuebunny/crossref_metadata_2025 huggingface dataset:
A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques
Authors: Harris Paul E. , Brasel Trevor , Massey Christopher , Herst C. V. , Burkholz Scott , Lloyd Peter , Blankenberg Tikoes , Bey Thomas M. , Carback Richard , Hodge Thomas , Ciotlos Serban , Wang Lu , Comer Jason E. , Rubsamen Reid
Published: April 2021

Background

Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.

Methods

Using a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108TCID50units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.

Results

Vaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.

Conclusions

We demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.

Graphical Abstract
Mountain radiations are not only rapid and recent: Ancient diversification of South American frog and lizard families related to Paleogene Andean orogeny and Cenozoic climate variations
Authors: Boschman Lydian M. , Condamine Fabien L.
Published: April 2021

Mountainous areas host a disproportionately large fraction of Earth’s biodiversity, suggesting a causal relationship between mountain building and biological diversification. Mountain clade radiations are generally associated with changes in environment, climate, and the increase in heterogeneity therein during mountain building. However, examining the causal relationship between mountain building and diversification is a complex challenge, because isolating the effects of surface uplift from other abiotic (climate) or biotic variables is not straightforward. In this study, we investigate the relative contributions of abiotic climate-driven (temperature) and geology-driven (elevation) drivers on evolutionary rates of ancient groups of organisms in the South American Andes. We present regional curves of Andean elevation based on a recent compilation of paleo-elevational data back to the Late Cretaceous, and analyse the diversification history of six Andean frog and lizard families that originated equally far back in time. For two clades (Aromobatidae and Leptodactylidae), we find that they diversified most rapidly during the early phase of mountain building (Late Cretaceous - Paleogene), when the first high-elevation habitats emerged in South America. The diversification of one clade (Centrolenidae) is correlated with Cenozoic temperature variations, with higher speciation rates during warm periods. The last three clades (Dendrobatidae, Hemiphractidae and Liolaemidae) are best explained by environment-independent diversification, although for Liolaemidae, an almost equally strong positive correlation was found between speciation and Andean elevation since the late Eocene. Our findings imply that throughout the long-lived history of surface uplift in the Andes, mountain building drove the diversification of different clades at different times, while not directly affecting other clades. Our study illustrates the importance of paleogeographic reconstructions that capture the complexity and heterogeneity of mountain building in our understanding of the effects that a changing environment plays in shaping biodiversity patterns observed today.

Highlights

We provide novel regional paleoelevation curves for the Andes back to the Late Cretaceous

The diversification history of six Andean-centered clades is studied

We find clade-specific responses to environmental changes

The impact of Andean uplift could reach further back in time than previously thought
Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
Authors: Li Xiaodong , Gordon Patrick J. , Gaynes John A. , Fuller Alexandra W. , Ringuette Randy , Santiago Clayton P. , Wallace Valerie A. , Blackshaw Seth , Li Pulin , Levine Edward M.
Published: April 2021

An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation.
Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells
Authors: Tamaoki Naritaka , Siebert Stefan , Maeda Takuya , Ha Ngoc-Han , Good Meghan L. , Huang Yin , Vodnala Suman Kumar , Haro-Mora Juan J. , Uchida Naoya , Tisdale John F. , Sweeney Colin L. , Choi Uimook , Brault Julie , Koontz Sherry , Malech Harry L. , Yamazaki Yasuhiro , Isonaka Risa , Goldstein David S. , Kimura Masaki , Takebe Takanori , Zou Jizhong , Stroncek David F. , Robey Pamela G. , Kruhlak Michael J. , Restifo Nicholas P. , Vizcardo Raul
Published: April 2021

The human definitive yolk sac is an important organ supporting the early developing embryo through nutrient supply and by facilitating the establishment of the embryonic circulatory system. However, the molecular and cellular biology of the human yolk sac remains largely obscure due to the lack of suitable in vitro models. Here, we show that human induced pluripotent stem cells (hiPSCs) co-cultured with various types of stromal cells as spheroids self-organize into yolk sac-like organoids without the addition of exogenous factors. Yolk sac-like organoids recapitulated a yolk sac specific cellular complement and structures as well as the functional ability to generate definitive hematopoietic progenitor cells (HPCs). Furthermore, sequential hemato-vascular ontogenesis could be observed during organoid formation. Notably, our organoid system can be performed in a scalable, autologous, and xeno-free condition, thereby providing an important model of human definitive yolk sac development and allows for efficient bulk generation of hiPSC-derived HPCs.
A closed-loop stimulation approach with real-time estimation of the instantaneous phase of neural oscillations by a Kalman filter
Authors: Onojima Takayuki , Kitajo Keiichi
Published: April 2021

We propose a novel method to estimate the instantaneous oscillatory phase to implement a real-time system for closed-loop sensory stimulation in electroencephalography (EEG) experiments. The method uses Kalman filter-based prediction to estimate current and future EEG signals. We tested the performance of our method in a real-time situation. We demonstrate that the performance of our method shows higher accuracy in predicting the EEG phase than the conventional autoregressive model-based method. A Kalman filter allows us to easily estimate the instantaneous phase of EEG oscillations based on the automatically estimated autoregressive model implemented in a real-time signal processing machine. The proposed method has a potential for versatile applications targeting the modulation of EEG phase dynamics and the plasticity of brain networks in relation to perceptual or cognitive functions.
Bacterial chaperone protein Hfq facilitates the annealing of sponge RNAs to small regulatory RNAs
Authors: Małecka Ewelina M. , Sobańska Daria , Olejniczak Mikołaj
Published: April 2021

Bacterial small RNAs (sRNAs) in association with the chaperone protein Hfq regulate the expression of many target mRNAs. Since sRNAs’ action is crucial to engender a response to changing environmental conditions, their activity needs to be regulated. One such mechanism occurs at posttranscriptional level and involves sponge RNAs (or anti-sRNAs) which sequester sRNAs affecting their regulatory output. Both types of RNAs were identified on Hfq, but it is not known how Hfq interacts with RNA sponges and stimulates their base-pairing with sRNAs. Here, we used biochemical methods to demonstrate that anti-sRNAs resemble sRNAs by their structure and their modes of Hfq binding. Hfq facilitates sponge RNA annealing to sRNA, and each surface of the protein plays a particular role in the process. Moreover, we found that the efficiency of sponge RNA interactions with sRNAs can be improved, therefore, we propose that natural RNA sponges might not sequester sRNAs optimally.
Accuracy and Precision of Social Relationship Indices
Authors: Mielke Alexander , Samuni Liran
Published: April 2021

Combining interaction rates of different social behaviours into social relationship indices to represent the structure of dyadic relationships on one underlying dimension is common practice in animal sociality studies. However, the properties of these relationship indices are not well explored – mainly because, for real-world social systems, the ‘true’ value of relationships is unobservable. Here, we use simulation studies to estimate the accuracy and precision of three relationship indices: the Dyadic Composite Sociality Index, the Composite Relationship Index, and the Dynamic Dyadic Sociality Index. We simulated one year of social interactions for multiple groups of 25 individuals and 4 interaction types with different properties, and tested the impact of different focal follow regimes, data densities and sampling conditions on the representation of social relationships. Accuracy and precision of social relationship indices were strongly driven by sample size, similar to simple interaction rates. Under the assumption that there was a clear, one-dimensional relationship underlying interactions, and that different interaction types constituting an index were highly correlated, indices indeed increased accuracy over single interaction rates for small sample sizes. Including uninformative constituting behaviours (i.e., those not highly correlated with the underlying relationship dimension) reduced the accuracy of all indices. The precision of each index (i.e., whether multiple simulated focal follow regimes achieve the same dyadic values for the same data) was generally poor and was driven by the precision of the least precise constituting behaviour, making them less precise than some single interaction rates. Our results showed that social relationship indices do not remove the need to have sufficient data for each individual constituting interaction type. Index quality was defined by the least accurate and precise constituting interaction type. Indices might only be useful if all constituting interaction rates are highly correlated and if there are clear indications that one dimension is sufficient to represent social relationships in a group.
Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals
Authors: Vanicek T , Reed MB , Unterholzner J , Klöbl M , Godbersen GM , Handschuh PA , Spurny B , Ritter V , Gryglewski G , Kraus C , Winkler D , Lanzenberger R , Seiger R
Published: April 2021

Background

Neuroplastic processes are influenced by selective serotonergic reuptake inhibitors, while learning in conjunction with the administration of serotonergic agents alters white matter microstructure in humans. The goal of this double-blind, placebo-controlled imaging study was to investigate the influence of escitalopram on white matter plasticity during (re)learning.

Methods

Seventy-one healthy individuals (age = 25.6±5.0, 43 females) underwent 3 diffusion magnetic resonance imaging sessions: at baseline, after 3-weeks of associative learning (emotional/non-emotional content) and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, subjects received daily escitalopram 10 mg or placebo orally. Statistical analysis was performed with statistical parametric mapping (SPM) and using sandwich estimator.

Results

A three-way and two-way rmANOVA was conducted to analyze the effects of escitalopram on AD, FA, MD and RD during the learning and relearning period. We found no significant three-way or two-way interactions for each DTI metrics (pFDR> 0.05), thus neither after 3 nor after 6 weeks we found significant changes in white matter microstructure.

Conclusion

We examined neither an effect of escitalopram nor learning (or relearning) interventions on different DTI metrics. The duration and intensity of study interventions (i.e. administration of escitalopram and learning as the relearning task) might have been chosen insufficiently to induce detectable alterations. Previous studies examining the effects of SSRIs on white matter tracts in humans are underrepresented, but do mainly yield towards non-significant findings. The results implicate that escitalopram does not impact white matter microstructures in healthy subjects.
Plant demographic knowledge is biased towards short-term studies of temperate-region herbaceous perennials
Authors: Römer Gesa , Dahlgren Johan P. , Salguero-Gómez Roberto , Stott Iain M. , Jones Owen R.
Published: April 2021

Plant population dynamics research has a long history, and data collection rates have increased through time. The inclusion of this information in databases enables researchers to investigate the drivers of demographic patterns globally and study life history evolution.

Studies aiming to generalise demographic patterns rely on data being derived from a representative sample of populations. However, the data are likely to be biased, both in terms of the species and ecoregions investigated and in how the original studies were conducted.

Matrix population models (MPMs) are a widely-used tool in plant demography, so an assessment of publications that have used MPMs is a convenient way to assess the distribution of plant demographic knowledge. We assessed bias in this knowledge using data from the COMPADRE Plant Matrix Database, which contains MPMs for almost 800 plant species.

We show that tree species and tropical ecoregions are under-represented, while herbaceous perennials and temperate ecoregions are over-represented. In addition, there is a positive association between the number of studies per country and the wealth of the country. Furthermore, we found a strong tendency towards low spatiotemporal replication: More than 50% of the studies were conducted over fewer than 4 years, and only 17% of the studies have replication across >3 sites. This limited spatiotemporal coverage means that the data may not be representative of the environmental conditions experienced by the species.

Synthesis: The biases and knowledge gaps we identify are a challenge for the progress of theory and limit the usefulness of current data for determining patterns that would be useful for conservation decisions, such as determining general responses to climate change. We urge researchers to close these knowledge gaps with novel data collection.
Kinetics and Mechanism of Fentanyl Dissociation from theµ-Opioid Receptor
Authors: Mahinthichaichan Paween , Vo Quynh N. , Ellis Christopher R. , Shen Jana
Published: April 2021

Driven by illicit fentanyl, opioid related deaths have reached the highest level in 2020. Currently, an opioid over-dose is resuscitated by the use of naloxone, which competitively binds and antagonizes theµ-opioid receptor (mOR). Thus, knowledge of the residence times of opioids at mOR and the unbinding mechanisms is valuable for assessing the effectiveness of naloxone. In the present study we calculate the fentanyl-mOR dissociation time and elucidate the mechanism by applying an enhanced sampling molecular dynamics (MD) technique. Two sets of metadynamics simulations with different initial structures were performed while accounting for the protonation state of the conserved H2976.52, which has been suggested to modulate the ligand-mOR affinity and binding mode. Surprisingly, with the Nδ-protonated H2976.52, fentanyl can descend as much as 10 Å below the level of the conserved D1473.32before escaping the receptor, and has a calculated residence timeτof 38 s. In contrast, with the N - and doubly protonated H2976.52, the calculatedτare 2.6 s and 0.9 s, respectively. Analysis suggests that formation of the piperidine–Hid297 hydrogen bond strengthens the hydrophobic contacts with the transmembrane helix (TM) 6, allowing fentanyl to explore a deep pocket. Considering the experimentalτof ∼4 min for fentanyl and the role of TM6 in mOR activation, we suggest that the deep insertion mechanism may be biologically relevant. The work paves the way for large-scale computational predictions of opioid dissociation rates to inform the regulatory decision. The profound role of the histidine protonation state found here may shift the paradigm in computational studies of ligand-receptor kinetics.
The oldest peracarid crustacean reveals a Late Devonian freshwater colonisation by isopod relatives
Authors: Robin N. , Gueriau P. , Luque J. , Jarvis D. , Daley A.C. , Vonk R.
Published: April 2021

Peracarida (e.g., woodlice & side-swimmers) are, together with their sister-group Eucarida (e.g. krill & decapods), the most speciose group of modern crustaceans, suggested to have appeared as early as the Ordovician. While eucarids incursion onto land consists of mainly freshwater and littoral grounds, some peracarids have evolved fully terrestrial ground-crawling ecologies, inhabiting even our gardens in temperate regions (e.g. pillbugs and sowbugs). Their fossil record extends back to the Carboniferous and consists mainly of marine occurrences. Here, we provide a complete re-analysis of a fossil arthropod –Oxyuropoda– reported in 1908 from the Late Devonian floodplains of Ireland, and left with unresolved systematic affinities despite a century of attempts at identification. Known from a single specimen preserved in two-dimensions, we analysed its anatomy using digital microscopy and multispectral macro-imaging to enhance contrast of morphological structures. The new anatomical characters and completeness ofOxyuropoda, together with a phylogenetic analysis with representatives of all major Eumalacostraca groups, indicate thatOxyuropodais a crown-peracarid, part of a clade including amphipods and isopods. As such,Oxyuropodais the oldest known Peracarida, and provides evidence that derived peracarids had an incursion into freshwater and terrestrial environments as early as the Famennian, more than 360 million years ago.
The F-box protein AFF1 regulates ARF protein accumulation to regulate auxin response
Authors: Jing Hongwei , Korasick David A. , Emenecker Ryan J. , Morffy Nicholas , Wilkinson Edward G. , Powers Samantha K. , Strader Lucia C.
Published: April 2021

Auxin critically regulates nearly every aspect of plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. Although ARF protein stability is regulated via the 26S proteasome, molecular mechanisms underlying ARF stability and turnover are unknown. Here, we report the identification and functional characterization of an F-box E3 ubiquitin ligase, which we have named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). AFF1 directly interacts with ARF19 and regulates its accumulation. Mutants defective inAFF1display ARF19 protein hyperaccumulation, attenuated auxin responsiveness, and developmental defects. Together, our data suggest a new mechanism, namely control of ARF protein stability, in regulating auxin response.
Targeting the mitochondrial RNA methyltransferase TRMT61B reveals new therapeutic opportunities in aneuploid cancer cells
Authors: Martín Alberto , Vilaplana-Marti Borja , Macías Rocío IR , Martínez-Ramírez Ángel , Cerezo Ana , Cabezas-Sainz Pablo , Garranzo Asensio Maria , Epifano Carolina , Amarilla Sandra , Gómez-Domínguez Déborah , Hernández Iván , Caleiras Eduardo , Camps Jordi , Barderas Rodrigo , Sánchez Laura , Velasco Susana , de Castro Ignacio Pérez
Published: April 2021

Chromosomal instability (CIN) is an important source of genetic and phenotypic variation that has been extensively reported as a critical cancer related property that improves tumor cell adaptation and survival. CIN and its immediate consequence, aneuploidy, provoke adverse effects on cellular homeostasis that need to be overcome by developing efficient anti-stress mechanisms. Perturbations in these safeguard responses might be detrimental for cancer cells and represent an important tumor specific Achilles heel since CIN and aneuploidy are very rare events in normal cells. On the other hand, epitranscriptomic marks catalyzed by different RNA modifying enzymes have been found to change under several stress insults. Although CIN and aneuploidy are important intracellular stressors, their biological connection with RNA modifications is pending to be determined. In anin silicosearch for new cancer biomarkers, we have identified TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. In the present work, we study the connection of this molecule with cancer and aneuploidy. First, we show increased protein amounts of TRMT61B in tumor cell lines with imbalanced karyotype as well as in different tumor types compared to unaffected control tissues. In addition, we demonstrate that depletion of TRMT61B in melanoma cells reduces cell proliferation either by fostering apoptosis and inhibiting autophagy in high-aneuploid (ANEhigh) cells or by inducing senescence in the case of low-aneuploid (ANElow) cell lines. Further, TRMT61B elimination compromises mitochondrial function and reduces the expression of several mitochondrial encoded proteins that are part of the electron transport chain. Finally, transwell and xenograft experiments revealed a reduced invasive and tumorigenic capacity upon TRMT61B depletion that strengthen the therapeutic value of this aneuploidy-associated biomarker. These results, which connect tumorigenesis, aneuploidy and mitochondrial RNA methylation, bring to the cancer field a new putative strategy to specifically target high aneuploid tumors.
Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation
Authors: Sarma Anish A. , Sarma Aartik , Csete Marie , Lee Peter P. , Doyle John C.
Published: April 2021

Dramatic variation in SARS-CoV-2 virulence and transmission between hosts has driven the COVID-19 pandemic. The complexity and dynamics of the immune response present a challenge to understanding variation in SARS-CoV-2 infections. To address this challenge, we apply control theory, a framework used to study complex feedback systems, to establish rigorous mathematical bounds on immune responses. Two mechanisms of SARS-CoV-2 biology are sufficient to create extreme variation between hosts: (1) a sparsely expressed host receptor and (2) potent, but not unique, suppression of interferon. The resulting model unifies disparate and unexplained features of the SARS-CoV-2 pandemic, predicts features of future viruses that threaten to cause pandemics, and identifies potential interventions.
Functional coupling between target selection and acquisition in the superior colliculus
Authors: Essig Jaclyn , Felsen Gidon
Published: April 2021

To survive in unpredictable environments, animals must continuously evaluate their surroundings for behavioral targets, such as food and shelter, and direct their movements to acquire those targets. Although the ability to accurately select and acquire spatial targets depends on a shared network of brain regions, how these processes are linked by neural circuits remains unknown. The superior colliculus (SC) mediates the selection of spatial targets and remains active during orienting movements to acquire targets, which suggests the underexamined possibility that common SC circuits underlie both selection and acquisition processes. Here, we test the hypothesis that SC functional circuitry couples target selection and acquisition using adefault motor plangenerated by selection-related neuronal activity. Single-unit recordings from intermediate and deep layer SC neurons in male mice performing a spatial choice task demonstrated that choice-predictive neurons, including optogenetically identified GABAergic SC neurons whose activity was causally related to target selection, exhibit increased activity during movement to the target. By strategically recording from both rostral and caudal SC neurons, we also revealed an overall caudal-to-rostral shift in activity as targets were acquired. Finally, we used an attractor model to examine how target selection activity in the SC could generate a rostral shift in activity during target acquisition using only intrinsic SC circuitry. Overall, our results suggest a functional coupling between SC circuits that underlie target selection and acquisition, elucidating a key mechanism for goal-directed behavior.

Significance Statement

The ability to quickly select and acquire spatial targets is essential to animal survival. Neural circuits underlying these processes are shared in an interconnected network of brain regions, however it is unclear how circuits link decision-making processes with motor commands to execute choices. Here, we examine single-unit activity in the superior colliculus (SC) as mice select and acquire spatial targets to test the hypothesis that choice-related activity promotes target acquisition by generating a default motor plan for orienting movements. By demonstrating that choice-predictive neurons increase their firing rates during movement and capturing the dynamics of SC activity with an attractor model of intrinsic SC circuitry, our results support a role for SC circuits in coupling target selection and acquisition.
Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking
Authors: Schmieder Stefanie S. , Tatituri Raju , Anderson Michael , Kelly Kate , Lencer Wayne I.
Published: April 2021

The complex sphingolipids exhibit a diversity of ceramide acyl chain structures that influence their trafficking and intracellular distributions, but how the cell discerns among the different ceramides to affect such sorting remains unknown. To address mechanism, we synthesized a library of GM1 glycosphingolipids with naturally varied acyl chains and quantitatively assessed their sorting among different endocytic pathways. We found that a stretch of at least 14 saturated carbons extending from C1 at the water-bilayer interface dictated lysosomal sorting by exclusion from endosome sorting tubules. Sorting to the lysosome by the C14*-motif was cholesterol dependent. Perturbations of the C14*-motif by unsaturation enabled GM1 entry into endosomal sorting tubules of the recycling and retrograde pathways independently of cholesterol. Unsaturation occurring beyond the C14*-motif in very long acyl chains rescued lysosomal sorting. These results define a structural motif underlying membrane organization of sphingolipids and implicate cholesterol-sphingolipid nanodomain formation in sorting mechanisms.
Implications of drift and rapid evolution on negative niche construction
Authors: Nguyen Phuong Linh , Costa Manon , Loeuille Nicolas
Published: April 2021

Organisms throughout their lives constantly modify their surrounding environment; such activities are often termed niche construction. An important property of niche construction is that its consequences can persist for a long period of time and several subsequent generations can be affected. This phenomenon is described as a time lag in niche construction, or ecological inheritance.

Studies have suggested that time lag in niche construction can help avoiding the tragedy of the commons. In other words, it can lead to evolution of contribution to a common good, which is associated with positive niche construction, or to the limitation of a common bad, which is associated with negative niche construction.

In this article, we will study the evolutionary consequences of incorporating time lags in a negative niche construction process: waste production. We consider a population that extrudes waste into its environment as it consumes resources to grow and reproduce. Higher consumption rates can lead to higher waste production. Individuals that adopt this selfish strategy are expected to be selected as toxic effects are equally shared among all individuals.

We show that indeed this tragedy of the commons persists in many cases and selfish strategies evolve in general. When evolution is rapid and intragenerational time lag is incorporated, however, selfish strategies are no longer favoured and strategies resulting in less waste production can be selected. Importantly, heavy pollution results in smaller population sizes, so that drift becomes more important than natural selection and limits the evolution of higher waste production.
SIBR-Cas enables host-independent and universal CRISPR genome engineering in bacteria
Authors: Patinios Constantinos , Creutzburg Sjoerd C.A. , Arifah Adini Q. , Pérez Belén A. , Ingham Colin J. , Kengen Servé W.M. , van der Oost John , Staals Raymond H.J.
Published: April 2021

CRISPR-Cas is a powerful tool for genome editing in bacteria. However, its efficacy is dependent on host factors (such as DNA repair pathways) and/or exogenous expression of recombinases. In this study, we mitigated these constraints by developing a simple and universal genome engineering tool for bacteria which we termed SIBR-Cas (Self-splicing Intron-Based Riboswitch-Cas). SIBR-Cas was generated from a mutant library of the theophylline-dependent self-splicing T4tdintron that allows for universal and inducible control over CRISPR-Cas counterselection. This control delays CRISPR-Cas counterselection, granting more time for the editing event (e.g., by homologous recombination) to occur. Without the use of exogenous recombinases, SIBR-Cas was successfully applied to knock-out several genes in three bacteria with poor homologous recombination systems. Compared to other genome engineering tools, SIBR-Cas is simple, tightly regulated and widely applicable for most (non-model) bacteria. Furthermore, we propose that SIBR can have a wider application as a universal gene expression and gene regulation control mechanism for any gene or RNA of interest in bacteria.
A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope
Authors: VanBlargan Laura A. , Adams Lucas J. , Liu Zhuoming , Chen Rita E. , Gilchuk Pavlo , Raju Saravanan , Smith Brittany K. , Zhao Haiyan , Case James Brett , Winkler Emma S. , Whitener Bradley M. , Droit Lindsay , Aziati Ishmael D. , Shi Pei-Yong , Creanga Adrian , Pegu Amarendra , Handley Scott A. , Wang David , Boon Adrianus C.M. , Crowe James E. , Whelan Sean P.J. , Fremont Daved H. , Diamond Michael S.
Published: April 2021

With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variantsin vivoand lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.
Assessment of dough rheological characteristics and soft bread roll quality of wheat flour incorporated with seaweed powder
Authors: Mamat Hasmadi Bin , Wan Chen Yeoh , Abdul Hamid Mansoor , Md Haque Akanda Jahurul , Pusiran Arif Kamisan , Zainol Mohamad Khairi
Published: April 2021

Purpose

This study aims to investigate the effects of incorporating seaweed composite flour on soft roll dough rheological characteristics and quality.

Design/methodology/approach

In this study, wheat flour was substituted with seaweed powder obtained from red seaweed (Kappaphycus alvarezii) at varying proportions (100:0; 99:1; 98:2; 97:3; 96:4; 95:5, 94:6, 93:7 and 92:8) and applied in soft roll production. The effects of seaweed composite flour were evaluated in terms of rheological characteristics, proximate composition and physical properties. The sensory characteristics of the soft rolls was evaluated by 40 untrained panellists by using a hedonic scale.

Findings

Farinograph analysis of the soft roll doughs showed that the incorporation of seaweed powder promoted an increase in water absorption, development time and mixing tolerance index, whereas it decreased stability time. Analysis of the proximate composition of the soft rolls showed that protein and carbohydrate contents decreased, but moisture, ash and crude fibre contents substantially increased. Dietary fibre increased with the increase in the proportion of seaweed powder added. The specific volume, bulk density and firmness of the soft rolls ranged from 3.01 to 5.48 cm3/g, 0.18 to 0.33 g/cm3 and 1.86 to 20.63 N, respectively. Sensory evaluation results showed that the mean score of sensory attributes decreased as the proportion of seaweed powder added was increased in the formulations. With regard to the overall acceptability, the panellists preferred the soft rolls with the least amount of seaweed powder added. The results of hedonic tests revealed that the panellists' acceptance decreased as higher amounts seaweed powder were added in the formulations.

Originality/value

This study showed that the seaweed powder of K. alvarezii can be utilised as an ingredient to improve the nutrient composition of baked products.
‘I know you shouldn't compare to other people, but I can’t do anything most people can’: Age, family and occupation categorisations in men’s reasoning about their anxiety in an online discussion forum
Authors: Drioli‐Phillips Phoebe G. , Le Couteur Amanda , Oxlad Melissa , Feo Rebecca , Scholz Brett
Published: April 2021

Despite its prevalence, men's anxiety is arguably under‐researched and poorly understood. The present study explores the reasoning provided by male posters to an online discussion forum about the source of their anxiety. Posts were collected from an Australian anxiety online discussion forum. This study utilises discursive psychology, informed by principles of membership categorisation analysis, to describe how age, occupation and family‐related identities can be invoked within common sense reasoning about the source of male anxiety. References to various identity categories were routinely employed by male forum posters in their representations of themselves, in order to describe the source of their anxiety in terms of a contrast between how they are, and how they should be. In examining accounts of anxiety and responses to those accounts, we can trace cultural knowledge about issues regarding men, masculinity and anxiety that those accounts make relevant. Findings illustrate how men's descriptions of the source of their anxiety should be understood as culturally bound and related to expectations and obligations associated with their social context and category memberships. By enhancing understandings of how men describe the source of their anxiety, this study offers insight into improving the identification and engagement of men experiencing anxiety in health services.
Splitting Climate Engineering Governance: How Problem Structure Shapes Institutional Design
Authors: Jinnah Sikina , Morrow David , Nicholson Simon
Published: April 2021

This article adds conceptual discipline to a well‐rehearsed but largely intuitive argument within the climate engineering community that carbon dioxide removal (CDR) and solar radiation management (SRM) should be treated separately – ‘split’ rather than ‘lumped’ – in policy discussions. Specifically, we build the first, theoretically derived argument for ‘splitting’. We do this by engaging a set of theoretical insights from the international relations literature, having to do with the relationship between problem structure and institutional design. Centrally, we apply some key elements of problem structure – which allows us to compare policy issues along variables such as geographic scope, costs, and actor number and asymmetries – to the cases of SRM and CDR. By analyzing their problem structures, we demonstrate that SRM and CDR are different in ways that are likely to yield different state preferences for institutional design, and thus policy proposals that split SRM and CDR are more likely to be adopted by states. In short, we construct a theoretical argument for ‘splitting’ SRM and CDR governance in global policy discussions.
Governing Artificial Intelligence in an Age of Inequality
Authors: Gehl Sampath Padmashree
Published: April 2021

This article seeks to position both AI‐based activities, and related policy developments, in the global South in light of a technology industry with desires for continuous expansion and self‐governance. The article proceeds along three themes. First, using field interviews and related information (in an anonymised manner), the article classifies expanding AI activities in several core sectors by businesses, governments and other agencies in the global South into three categories. Next, it reviews the current AI policy priorities and positions in developing countries, showing how the introduction of AI has been punctuated by considerations of digital cannibalization by large firms from the North at the expense of a full‐fledged debate on privacy and data protection. By showing how AI exemplifies structural inequality in the global South, the article identifies four critical departure points in developing countries that make the expanding use of AI a matter of concern. While many of challenges posed by AI are somewhat universal, the article argues that their ramifications can be much worse in the global South. Countering these will require policy frameworks that factor in privacy protection in a more accountable manner. It concludes with suggestions for a more nuanced debate on industrialisation, privacy protection and development.
Prior use of therapeutic anticoagulation does not protect against COVID‐19 related clinical outcomes in hospitalized patients: A propensity score‐matched cohort study
Authors: Spiegelenberg Janneke P. , van Gelder Marleen M. H. J. , Maas Martje L. , Hovens Marcel M. C. , Esselink Anne , Dofferhoff Anton S. M. , Janssen Rob , van de Maat Josephine , Janssen Nico , Blaauw Marc , Hassing Robert‐Jan , van Apeldoorn Marjan , Kerckhoffs Angèle , Veerman Karin , Hoogerwerf Jacobien , Kramers Cornelis , Leentjens Jenneke
Published: April 2021

The hypercoagulable state observed in COVID‐19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID‐19 patients. This study included 1154 COVID‐19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. In total, 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (risk ratio 1.02 [95% confidence interval; 0.80–1.30]) or length of hospital stay (7.0 [4–12]vs. 7.0 [4–12] days,P= .69), although we observed a lower risk of pulmonary embolism (0.19 [0.05–0.80]). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID‐19 patients.
Productivity Gap and Inward FDI Spillovers: Theory and Evidence from China
Authors: Shen Jim Huangnan , Wang Hao , Lin Steve Chu‐Chia
Published: April 2021

This paper constructs a two‐stage sequential game model to shed light on the spillover effect of inward FDI on the efficiency of domestic firms in host countries. Our model shows that, given an optimal joint‐venture policy made by foreign firms, the impact of the spillover effect of inward FDI is contingent upon the productivity gap between the domestic firms and foreign ones. In particular, we demonstrate that the spillover effect of inward FDI varies negatively with the productivity gap between domestic low‐productivity firms and foreign firms but works in the opposite way for high‐productivity firms. This suggests that once the productivity gap widens, the entry of foreign firms will increase the efficiency of high‐productivity firms but reduce the efficiency of low‐productivity firms. In support of our theoretical model, we provide robust empirical results by using the dataset of annual survey of Chinese industrial enterprises.
Assessing Market Competition in the Chinese Banking Industry Based on a Conjectural Variation Model
Authors: Zhou Xiangyi , Pei Zheng , Qin Botao
Published: April 2021

Most literature on market competition in the banking industry neglects to address strategic interaction among banks. This paper studies interaction among Chinese banks by dividing banks into two groups: dominant banks (the “Big 5” state‐owned banks) and small‐ and medium‐sized banks (joint‐stock banks and large city commercial banks). We test an oligopolistic model with conjectural variation developed by Spiller and Favaro (1984). Using data from 2007 to 2016, we find that banking competition is not in the form of Stackelberg competition per se. Some strategic interactions exist between small‐ and medium‐sized banks and the largest state‐owned bank. We also study the effect of interest rate deregulation on oligopolies' strategic interactions. Our results show that interest rate deregulation stimulates banking competition by reducing collusiveness among the dominant state‐owned banks and enhancing the market power of small and medium banks.
“Ex‐vivo” T‐cell depletion in allogeneic hematopoietic stem cell transplantation: New clinical approaches for old challenges
Authors: Diaz Miguel A. , Gasior Mercedes , Molina Blanca , Pérez‐Martínez Antonio , González‐Vicent Marta
Published: April 2021

Allogeneic transplantation still remains as standard of care for patients with high‐risk hematological malignancies at diagnosis or after relapse. However, GvHD remains yet as the most relevant clinical complication in the early post‐transplant period. TCD allogeneic transplant is now considered a valid option to reduce severe GvHD and to provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.
Homozygous SCN1B variants causing early infantile epileptic encephalopathy 52 affect voltage‐gated sodium channel function
Authors: Scala Marcello , Efthymiou Stephanie , Sultan Tipu , De Waele Jolien , Panciroli Marta , Salpietro Vincenzo , Maroofian Reza , Striano Pasquale , Van Petegem Filip , Houlden Henry , Bosmans Frank
Published: April 2021

We identified nine patients from four unrelated families harboring three biallelic variants in SCN1B (NM_001037.5: c.136C>T; p.[Arg46Cys], c.178C>T; p.[Arg60Cys], and c.472G>A; p.[Val158Met]). All subjects presented with early infantile epileptic encephalopathy 52 (EIEE52), a rare, severe developmental and epileptic encephalopathy featuring infantile onset refractory seizures followed by developmental stagnation or regression. Because SCN1B influences neuronal excitability through modulation of voltage‐gated sodium (NaV) channel function, we examined the effects of human SCN1BR46C (β1R46C), SCN1BR60C (β1R60C), and SCN1BV158M (β1V158M) on the three predominant brain NaV channel subtypes NaV1.1 (SCN1A), NaV1.2 (SCN2A), and NaV1.6 (SCN8A). We observed a shift toward more depolarizing potentials of conductance–voltage relationships (NaV1.2/β1R46C, NaV1.2/β1R60C, NaV1.6/β1R46C, NaV1.6/β1R60C, and NaV1.6/β1V158M) and channel availability (NaV1.1/β1R46C, NaV1.1/β1V158M, NaV1.2/β1R46C, NaV1.2/β1R60C, and NaV1.6/β1V158M), and detected a slower recovery from fast inactivation for NaV1.1/β1V158M. Combined with modeling data indicating perturbation‐induced structural changes in β1, these results suggest that the SCN1B variants reported here can disrupt normal NaV channel function in the brain, which may contribute to EIEE52.
Being Heard and Remembered: Young Adults’ Experiences of Recognition in the Social and Health Care Systems in Denmark
Authors: Andersen Julie Høgsgaard , Tjørnhøj‐Thomsen Tine , Reventlow Susanne , Davidsen Annette Sofie
Published: April 2021

This article draws on ethnographic material from a study among young Danish adults who have complex psychosocial problems and are not engaged in education or employment. Engaging the concepts of recognition (Honneth 2003, 2006) and care (Tronto 1994), we examine the young adults’ experiences of attitudinal, practical and relational aspects of encounters with professionals and services in the social and health care systems. We track how the young adults are socially visible or invisible as individuals depending on whether professionals show a genuine interest in the young adults’ specific stories and help meeting their needs over time. Social visibility is a prerequisite of recognition (Honneth 2003). We argue that at stake in the young adults’ encounters with professionals and services is the recognition of them as equal members of society, who deserve help with overcoming their problems and have something to contribute with. We examine the consequences of lack of recognition, and we conclude that paradoxically the efforts made by the system to help the young adults in some cases contribute to their experience of marginalization.