bluuebunny/crossref_metadata_2025 huggingface dataset:
Reopening Universities without Testing During COVID-19: Evaluating a Possible Alternative Strategy in Low Risk Countries
Authors: Xi Jing Yang (Sunny) , Chan Wai Kin (Victor)
Published: March 2021

The safety of students worldwide remains a key issue during COVID-19. The reopening of universities in high risk countries during Fall 2020 resulted in numerous outbreaks. While regular screening and testing on campus can prevent the transmission of SARS-CoV-2, they are extremely challenging to implement due to various reasons such as cost and logistics. However, for low risk countries with minimal to no community spread, our study suggests that universities can fully reopen without testing, if students self-quarantine for 14 days on arrival and adopt proper nonpharmaceutical interventions (NPIs). This alternative strategy might save institutions millions of dollars. We adopt agent-based simulation to model virus transmission on campus and test the effectiveness of several NPIs when school reopens. Assuming one initially infected student, results indicate that transmission between roommates causes the most infections with visitors, ground floors, and elevators, being the next main contributors. Limiting density and/or population are not impactful at flattening the curve. However, adopting masks, minimizing movement, and increasing the frequency of cleaning can effectively minimize infection and prevent outbreak, allowing for classes and activities to resume as normal.
Day by day symptoms following positive and negative PCR tests for SARS-CoV-2 in non-hospitalised health-care workers: a 90-day follow-up study
Authors: Nielsen Kent J. , Vestergaard Jesper Medom , Schlünssen Vivi , Bonde Jens Peter , Kaspersen Kathrine Agergård , Biering Karin , Carstensen Ole , Greve Thomas , Hansen Karoline Kærgaard , Dalbøge Annett , Flachs Esben Meulengracht , Jespersen Sanne , Hansen Mette Lausten , Mikkelsen Susan , Thomsen Marianne Kragh , Redder Jacob Dvinge , Würtz Else Toft , Østergaard Lars , Erikstrup Christian , Kolstad Henrik Albert
Published: March 2021

Background

Little is known about the long-term course of symptoms for mild coronavirus disease 2019 (COVID-19) when accounting for symptoms due to other causes. We aimed to compare symptoms day by day for non-hospitalised individuals who tested positive and negative with polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

We followed 210 test-positive and 630 individually matched test-negative health-care workers of the Central Denmark Region up to 90 days after the test, April-June 2020. They daily reported seven COVID-19 related symptoms. Symptom courses were compared graphically and by conditional multivariable logistic regression.

Results

Thirty % of test-positive and close to zero of test-negative participants reported a reduced sense of taste and smell during all 90 days of follow-up (adjusted odds ratio [aOR] 86.07, 95% CI 22.86-323). Dyspnoea was reported by an initial 20% of test-positive with a gradual decline to about 5% after 30 days without ever reaching the level of the test-negative participants (aOR 6.88, 95% CI 2.41-19.63). Cough, headache, sore throat, muscle aches, and fever were temporarily more prevalent among the test positive participants, but after 30 days, no increases were seen. Women and participants aged 45 years or older tended to be more susceptible to SARS-CoV-2 infection.

Conclusion

Prevalence of long-lasting reduced sense of taste and smell is highly increased after being diagnosed with mild COVID-19. This pattern is also seen for dyspnoea at a low level but not for cough, sore throat, headache, muscle ache or pain, or fever.

Key messages

Reduced sense of taste and smell is present at a highly increased level of 30% during 90 days after testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).

Test-positive participants experience dyspnoea persistently more often than test-negative participants but affect only few.

The prevalence of cough, sore throat, headache, muscle ache or pain, and fever following a positive test reach the level seen after a negative test within 30 days.

Women and participants aged 45 years or older tend to be more susceptible to symptoms following SARS-CoV-2 infection.
Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study
Authors: McKeigue Paul M , McAllister David A , Caldwell David , Gribben Ciara , Bishop Jen , McGurnaghan Stuart , Armstrong Matthew , Delvaux Joke , Colville Sam , Hutchinson Sharon , Robertson Chris , Lone Nazir , McMenamin Jim , Goldberg David , Colhoun Helen M
Published: March 2021

Background

Clinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate: (1) the risk of severe COVID-19 in those eligible for shielding, and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population.

Methods

All 178578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1744283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal.

Results

With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. To test for causality, a case-crossover analysis was undertaken; with less recent exposure only (15 to 24 days before first testing positive) as reference category, the rate ratio associated with recent exposure only was 5.9 (95% CI 3.6 to 9.7). The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020.

Conclusions

The effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. For solid organ transplant recipients, in whom the efficacy of vaccines is uncertain, these results support a policy of offering vaccination to household contacts. Mitigating the impact of the epidemic requires control of nosocomial transmission.
Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity
Authors: Izgi Hamit , Han DingDing , Isildak Ulas , Huang Shuyun , Kocabiyik Ece , Khaitovich Philipp , Somel Mehmet , Dönertaş Handan Melike
Published: March 2021

Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we termDivergence followed byConvergence, or DiCo. We found that DiCo was most prevalent among tissue-specific genes and associated with loss of tissue identity, which is confirmed using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell type composition and also by cell-autonomous expression changes within particular cell types.
Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly
Authors: Credle Joel J. , Gunn Jonathan , Sangkhapreecha Puwanat , Monaco Daniel R. , Zheng Xuwen Alice , Tsai Hung-Ji , Wilbon Azaan , Morgenlander William R. , Dong Yi , Jayaraman Sahana , Tosi Lorenzo , Parekkadan Biju , Baer Alan N. , Roederer Mario , Bloch Evan M. , Tobian Aaron A. R. , Zyskind Israel , Silverberg Jonathan I. , Rosenberg Avi Z. , Cox Andrea L. , Lloyd Tom , Mammen Andrew L. , Larman H. Benjamin
Published: March 2021

Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-λ3) autoantibodies. At-risk individuals with anti-IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation.

One-Sentence Summary

Molecular Indexing of Proteins by Self Assembly (MIPSA) identifies neutralizing IFNL3 autoantibodies in patients with severe COVID-19.

Graphical Abstract
Hematopoietic progenitors passing through early embryonic CD4-positive stage are long-lived and give rise to myeloid and lymphoid progeny
Authors: Apostolov Apostol K. , Marie Julien C.
Published: March 2021

This manuscript has been withdrawn as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Body mass, temperature, and depth shape the maximum intrinsic rate of population increase in sharks and rays
Authors: A. Pardo Sebastián , Dulvy Nicholas K.
Published: March 2021

An important challenge in ecology is to understand variation in species’ maximum intrinsic rate of population increase,rmax, not least becausermaxunderpins our understanding of the limits of fishing, recovery potential, and ultimately extinction risk. Across many vertebrates, terrestrial and aquatic, body mass and environmental temperature across important correlatesrmaxacross species. In sharks and rays, specifically,rmaxis known be lower in larger species, but also in deep-sea ones. We use an information-theoretic approach that accounts for phylogenetic relatedness to evaluate the relative importance of body mass, temperature and depth onrmax. We show that both temperature and depth have separate effects on shark and rayrmaxestimates, such that species living in deeper waters have lowerrmax. Furthermore, temperature also correlates with changes in the mass scaling coefficient, suggesting that as body size increases, decreases inrmaxare much steeper for species in warmer waters. These findings suggest that there (as-yet understood) depth-related processes that limit the maximum rate at which populations can grow in deep sea sharks and rays. While the deep ocean is associated with colder temperatures, other factors that are independent of temperature, such as food availability and physiological constraints, may influence the lowrmaxobserved in deep sea sharks and rays. Our study lays the foundation for predicting the intrinsic limit of fishing, recovery potential, and extinction risk species based on easily accessible environmental information such as temperature and depth, particularly for data-poor species.
Genome-wide screens identify calcium signaling as a key regulator of IgE+plasma cell differentiation and survival
Authors: Newman Rebecca , Tolar Pavel
Published: March 2021

IgE antibodies protect against toxins and parasites, however, they also mediate allergic reactions. In contrast to other antibody isotypes, B cells switched to IgE respond transiently and do not give rise to long-lived plasma cells (PCs) or memory B cells. Although the intrinsic differences of IgE+B cells have been linked to signaling by the IgE-B cell receptor (BCR), the molecular pathways controlling their behavior remain poorly understood. Here we employ whole-genome CRISPR screening to identify genes regulating IgE+B cell proliferation, survival and differentiation into PCs. We show that IgE+B cells are selectively suppressed by the IgE-BCR signaling to intracellular calcium, which inhibits PC differentiation and limits their lifespan after differentiation. Consequently, manipulation of calcium signalingin vivoenhances IgE+PC responses. Insights from this pathway shed new light on the self-limiting character of IgE responses and open new avenues to eliminate IgE+PCs in allergy.
A study of the neuronal injury biomarkers pNF-H and UCHL1 in serum, CSF and urine in a cohort of thoracic endovascular aortic repair (TEVAR) patients
Authors: Beck Adam , Marin Vedrana , Deng Jay , Madorsky Irina , Ren Bin , Guo Yichen , Neal Dan , Shaw Gerry
Published: March 2021

A collection of longitudinal serum, cerebrospinal fluid (CSF) and urine samples were collected from a cohort of 50 patients undergoing thoracic endovascular aortic repairs (TEVAR). Samples were taken multiple time per day out to 5 days post operation and were probed with novel electrochemiluminescent assays specific for the phosphorylated axonal form of the major neurofilament subunit NF-H (pNF-H) and for ubiquitin C-terminal hydrolase 1 (UCHL1). Control blood samples showed small signals for pNF-H and in some cases rather larger signals for UCHL1. The presence of UCHL1 in these control blood samples was convincingly verified by western blotting with multiple well characterized UCHL1 antibodies and by mass spectroscopy. Elevated levels of both pNF-H and UCHL1 in blood and CSF in recovering TEVAR patients were associated with poorer outcomes. In particular release of UCHL1 into blood over several hours following TEVAR and peaking at any time over 1 ng/ml was a very strong predictor of patient death and was associated with renal failure and spinal cord ischemia (SCI). An unexpected finding was that high levels of UCHL1 were detected in certain urine samples, again in association with SCI, renal failure and poor patient outcome. We also present epitope mapping data on the UCHL1 monoclonal antibodies used including data on the widely used commercially available MCA-BH7. These studies suggest that measurement of the levels of both proteins in the blood, CSF and urine of TEVAR patients may be of clinical utility. However this study also raises questions about the origin and significance of UCHL1 both in control blood, in patient blood samples and in urine.
A New Straightforward Method for Automated Segmentation of Trabecular Bone from Cortical Bone in Diverse and Challenging Morphologies
Authors: Herbst Eva C. , Felder Alessandro A. , Evans Lucinda A. E. , Ajami Sara , Javaheri Behzad , Pitsillides Andrew A.
Published: March 2021

Many physiological, biomechanical, evolutionary and clinical studies that explore skeletal structure and function require successful separation of trabecular from cortical compartments of a bone that has been imaged by X-ray micro-computed tomography (microCT) prior to analysis. Separation is often time-consuming, involves user bias and needs manual sub-division of these two similarly radio-opaque compartments. We have developed an objective, automated protocol which reduces user bias and enables straightforward, user-friendly segmentation of trabecular from cortical bone without requiring sophisticated programming expertise. This method can conveniently be used as a “recipe” in commercial programmes (Avizo herein) and applied to a variety of datasets. Here, we characterise and share this recipe, and demonstrate its application to a range of murine and human bone types, including normal and osteoarthritic specimens, and bones with distinct embryonic origins and spanning a range of ages. We validate the method by testing inter-user bias during the scan preparation steps and confirm utility in the architecturally challenging analysis of growing murine epiphyses. We also report details of the recipe, so that other groups can readily re-create a similar method in open access programs. Our aim is that this method will be adopted widely to create a more standardized and time efficient method of segmenting trabecular and cortical bone.
High-content screening of coronavirus genes for innate immune suppression reveals enhanced potency of SARS-CoV-2 proteins
Authors: Olson Erika J. , Brown David M. , Chang Timothy Z. , Ding Lin , Ng Tai L. , Weiss H. Sloane , Koide Yukiye , Koch Peter , Rollins Nathan , Mach Pia , Meisinger Tobias , Bricken Trenton , Rollins Joshua , Zhang Yun , Molloy Colin , Zhang Yun , Queenan Bridget N. , Mitchison Timothy , Marks Debora , Way Jeffrey C. , Glass John I. , Silver Pamela A.
Published: March 2021

Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2, SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e.g., NSP1, Orf6, NSP3, and NSP5) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.
DeepMOCCA: A pan-cancer prognostic model identifies personalized prognostic markers through graph attention and multi-omics data integration
Authors: Althubaiti Sara , Kulmanov Maxat , Liu Yang , Gkoutos Georgios V , Schofield Paul , Hoehndorf Robert
Published: March 2021

Combining multiple types of genomic, transcriptional, proteomic, and epigenetic datasets has the potential to reveal biological mechanisms across multiple scales, and may lead to more accurate models for clinical decision support. Developing efficient models that can derive clinical outcomes from high-dimensional data remains problematical; challenges include the integration of multiple types of omics data, inclusion of biological background knowledge, and developing machine learning models that are able to deal with this high dimensionality while having only few samples from which to derive a model. We developed DeepMOCCA, a framework for multi-omics cancer analysis. We combine different types of omics data using biological relations between genes, transcripts, and proteins, combine the multi-omics data with background knowledge in the form of protein–protein interaction networks, and use graph convolution neural networks to exploit this combination of multi-omics data and background knowledge. DeepMOCCA predicts survival time for individual patient samples for 33 cancer types and outperforms most existing survival prediction methods. Moreover, DeepMOCCA includes a graph attention mechanism which prioritizes driver genes and prognostic markers in a patient-specific manner; the attention mechanism can be used to identify drivers and prognostic markers within cohorts and individual patients.

Author summary

Linking the features of tumors to a prognosis for the patient is a critical part of managing cancer. Many methods have been applied to this problem but we still lack accurate prognostic markers for many cancers. We now have more information than ever before on the state of the cancer genome, the epigenetic changes in tumors, and gene expression at both RNA and protein levels. Here, we address the question of how this data can be used to predict cancer survival and discover which tumor genes make the greatest contribution to the prognosis in individual tumor samples. We have developed a computational model, DeepMOCCA, that uses artificial neural networks underpinned by a large graph constructed from background knowledge concerning the functional interactions between genes and their products. We show that with our method, DeepMOCCA can predict cancer survival time based entirely on features of the tumor at a cellular and molecular level. The method confirms many existing genes that affect survival but for some cancers suggests new genes, either not implicated in survival before or not known to be important in that particular cancer. The ability to predict the important features in individual tumors provided by our method raises the possibility of personalized therapy based on the gene or network dominating the prognosis for that patient.
Predicting biological pathways of chemical compounds with a profile-inspired aproach
Authors: Lopez-Ibañez Javier , Pazos Florencio , Chagoyen Monica
Published: March 2021

Assignment of chemical compounds to biological pathways is a crucial step to understand the relationship between the chemical repertory of an organism and its biology. Protein sequence profiles are very successful in capturing the main structural and functional features of a protein family, and can be used to assign new members to it based on matching of their sequences against these profiles. In this work, we extend this idea to chemical compounds, constructing a profile-inspired model for a set of related metabolites (those in the same biological pathway), based on a fragment-based vectorial representation of their chemical structures. We use this representation to predict the biological pathway of a chemical compound with good overall accuracy (AUC 0.74-0.90 depending on the database tested), and analyzed some factors that affect performance. The approach, which is compared with equivalent methods, can in addition detect those molecular fragments characteristic of a pathway. The method is available as a graphical interactive web serverhttp://csbg.cnb.csic.es/iFragMent
Decline in large-seeded species in Danish grasslands over an eight-year period
Authors: Damgaard Christian
Published: March 2021

A time-series analysis of cover data from 236 Danish grassland sites demonstrated community selection on seed mass. Across four grassland habitat types and during an eight-year period there was a significant decline in large-seeded species. In the analysis, the continuous seed size variable was used to group plant species into functional types. This method was chosen in order to account for the sampling process of the abundance data, and is in contrast to most other analyses of trait selection, where the community weighted mean of the traits is used as the dependent variable. Generally, little is known on the causes for seed size community selection in semi-natural grasslands that are not subjected to successional processes.
Transient beta activity and connectivity during sustained motor behaviour
Authors: Echeverria-Altuna Irene , Quinn Andrew J. , Zokaei Nahid , Woolrich Mark W. , Nobre Anna C. , van Ede Freek
Published: March 2021

Neural oscillations are thought to play a central role in orchestrating activity states between distant neural populations. In humans, long-range neural connectivity has been particularly well characterised for 13-30 Hz beta activity which becomes phase coupled between the motor cortex and the contralateral muscle during isometric contraction. Based on this and related observations, beta activity and connectivity have been linked to sustaining stable cognitive and motor states – or the ‘status quo’ – in the brain. Recently, however, beta activity has been shown to be short-lived, as opposed to sustained – though so far this has been reported for regional beta activity in tasks without sustained motor demands. Here, we measured magnetoencephalography (MEG) and electromyography (EMG) in 18 human participants performing an isometric-contraction (gripping) task designed to yield sustained behavioural output. If cortico-muscular beta connectivity is directly responsible for sustaining a stable motor state, then beta activity should be (or become) sustained in this context. In contrast, we found that beta activity and connectivity with the downstream muscle were transient, even when participants engaged in sustained gripping. Moreover, we found that sustained motor requirements did not prolong beta-event duration in comparison to rest. These findings suggest that long-range neural synchronisation may entail short ‘bursts’ of frequency-specific connectivity, even when task demands – and behaviour – are sustained.

Highlights

Trial-average 13-30 Hz beta activity and connectivity with the muscle appear sustained during stable motor behaviour

Single-trial beta activity and connectivity are short-lived, even when motor behaviour is sustained

Sustained task demands do not prolong beta-event duration in comparison to resting state
Cooperative Stabilization of Close-Contact Zones Leads to Sensitivity and Selectivity in T-Cell Recognition
Authors: Różycki Bartosz , Weikl Thomas R.
Published: March 2021

T cells are sensitive to 1 to 10 foreign-peptide-MHC complexes among a vast majority of self-peptide-MHC complexes, and discriminate selectively between peptide-MHC complexes that differ not much in their binding affinity to T-cell receptors (TCRs). Quantitative models that aim to explain this sensitivity and selectivity largely focus on single TCR/peptide-MHC complexes, but T cell adhesion involves a multitude of different complexes. In this article, we demonstrate in a three-dimensional computational model of T-cell adhesion that the cooperative stabilization of close-contact zones is sensitive to 1 to 3 foreign-peptide-MHC complexes and occurs at a rather sharp threshold affinity of these complexes, which implies selectivity. In these close-contact zones with lateral extensions of hundred to several hundred nanometers, few TCR/foreign-peptide-MHC complexes and many TCR/self-peptide-MHC complexes are segregated from LFA-1/ICAM-1 complexes that form at larger membrane separations. Previous high-resolution microscopy experiments indicate that the sensitivity and selectivity in the formation of closed-contact zones reported here is relevant for T-cell recognition, because the stabilization of close-contact zones by foreign, agonist peptide-MHC complexes precedes T-cell signaling and activation in the experiments.
Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85
Authors: Lauzon-Joset Jean-Francois , Mincham Kyle T , Scott Naomi M , Khandan Yasmine , Stumbles Philip A , Holt Patrick G , Strickland Deborah H
Published: March 2021

Objectives

Incomplete maturation of immune regulatory functions at birth are antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the benign microbial-derived immune modulating agent OM-85 during pregnancy promotes accelerated maturation of immune regulatory networks in the developing fetal bone marrow. Here, we aimed to establish proof-of-concept that this would enhance resilience to severe early life respiratory viral infection during the neonatal period.

Methods

Pregnant BALB/c mice were treated orally with OM-85 during gestation and their offspring infected intranasally with a mouse-adapted rhinovirus (vMC0) at postnatal day 2. We then assessed clinical course, lung viral titres and lung immune parameters to determine whether offspring from OM-85 treated mothers demonstrate enhanced immune protection against neonatal vMC0infection.

Results

Offspring from OM-85 treated mothers display enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with a concomitant reduction in the exaggerated nature of the ensuing immune response. These treatment effects were associated with accelerated postnatal myeloid cell seeding of neonatal lungs and enhanced expression of microbial sensing receptors in lung tissues, coupled in particular with enhanced capacity to rapidly expand and maintain networks of lung dendritic cells expressing function-associated markers crucial for maintenance of local immune homeostasis in the face of pathogen challenge.

Conclusion

Maternal OM-85 treatment may represent a novel therapeutic strategy to reduce the burden, and potential long-term sequlae, of severe neonatal respiratory viral infection by accelerating development of innate immune competence.
Slow rTMS to the left DLPFC enhances verbal memory formation
Authors: van der Plas Mircea , Braun Verena , Stauch Benjamin Johannes , Hanslmayr Simon
Published: March 2021

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. 40 healthy human participants engaged in a list learning paradigm. Half of the subjects (N=20) received 1 Hz rTMS to the left DLPFC while the other half (N=20) received 1 Hz rTMS to the vertex and served as a control group. Subjects receiving left DLPFC stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a double-blind within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state which is known to be beneficial for memory encoding. Further analysis indicated, that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.
Multiple targets of balancing selection inLeishmania donovanicomplex parasites
Authors: Grace Cooper Alastair , Forrester Sarah , Silva Vladimir Costa , Aare Aleksander , Kilford Hannah , Chew Yen Peng , James Sally , Costa Dorcas L. , Mottram Jeremy C. , Costa Carlos C. H. N. , Jeffares Daniel C.
Published: March 2021

TheLeishmania donovanispecies complex are the causative agents of visceral leishmaniasis, which cause 20-40,000 fatalities a year. Here, we conduct a screen for balancing selection in this species complex. We used 387 publicly-availableL. donovaniandL. infantumgenomes, and sequence 93 isolates ofL. infantumfrom Brazil to describe the global diversity of this species complex. We identify five genetically-distinct populations that are sufficiently represented by genomic data to search for signatures of selection. We find that signals of balancing selection are generally not shared between populations, consistent with transient adaptive events, rather than long-term balancing selection. We then apply multiple diversity metrics to identify candidate genes with robust signatures of balancing selection, identifying a curated set of 19 genes with robust signatures. These include zeta toxin, nodulin-like and flagellum attachment proteins. This study highlights the extent of genetic divergence betweenL. donovani complexparasites and provides genes for further study.
A pan-ontology view of machine-derived knowledge representations and feedback mechanisms for curation
Authors: Konopka Tomasz , Smedley Damian
Published: March 2021

Biomedical ontologies are established tools that organize knowledge in specialized research areas. They can also be used to train machine-learning models. However, it is unclear to what extent representations of ontology concepts learned by machine-learning models capture the relationships intended by ontology curators. It is also unclear whether the representations can provide insights to improve the curation process. Here, we investigate ontologies from across the spectrum of biological research and assess the concordance of formal ontology hierarchies with representations based on plain-text definitions. By comparing the internal properties of each ontology, we describe general patterns across the pan-ontology landscape and pinpoint areas with discrepancies in individual domains. We suggest specific mechanisms through which machine-learning approaches can lead to clarifications of ontology definitions. Synchronizing patterns in machine-derived representations with those intended by the ontology curators will likely streamline the use of ontologies in downstream applications.
Spatio-temporal modelling for the evaluation of an altered Indian saline Ramsar site and its drivers for ecosystem management and restoration
Authors: Naik Rajashree , Sharma L.K.
Published: March 2021

Saline wetlands are keystone ecosystems in arid and semi-arid landscapes that are currently under severe threat. This study conducted spatio-temporal modelling of the largest saline Ramsar site of India, in Sambhar wetland from 1963-2059. One CORONA aerial photograph of 1963 and Landsat images of 1972, 1981, 1992, 2009, and 2019 were acquired and classified under 8 classes as Aravalli, barren land, saline soil, salt crust, saltpans, waterbody, settlement, and vegetation for spatial modelling integrated with bird census, soil-water parameters, GPS locations, and photographs. Past decadal area statistics state reduction of waterbody from 30.7 to 3.4% at constant rate (4.23%) to saline soil. Saline soil increased from 12.4 to 21.7% and saline soil converted to barren land from 45.4 to 49.6%; saltpans from 7.4 to 14% and settlement from increased 0.1 to 1.3% till 2019. Future predictions hint at a net increase of 20% by wetland, vegetation by 30%, settlement by 40%, saltpan by 10%, barren land by 5%, and net loss of 20%, each by Aravalli and salt crust. The biggest loss of 120% was seen by saline soil converted to barren land. Notably, 40% of the current wetland will be lost by 2059. Additionally, soil-water parameters result state a loss of saline character of wetland ecosystem; subsequently bird statistics indicate a shift in migratory birds disturbing the wetland food web. India has been losing a critical habitat of migratory birds, halophytes, and halophiles, along with livelihood. This study looks to bridge the missing link from local to global wetland ecological disconnect, providing thereby lake management and restoration strategies.
Panakeia - A universal tool for bacterial pangenome analysis
Authors: Beier Sina , Thomson Nicholas R.
Published: March 2021

Abstract

We present Panakeia, a tool which strives to be easy to use and providing a detailed view of the pangenome structure which can efficiently be utilised for discovery, or further in-depth analysis, of features of interest. It analyses synteny and multiple structural patterns of the pangenome, giving insights into the biological diversity and evolution of the studied taxon. Panakeia hence provides both broad and detailed information on the structure of a pangenome, for diverse and highly clonal populations of bacteria. Development of new pan-genome analysis tools is important, as the pangenome of a microbial species has become an important method to define the diversity of a selected taxon, most commonly a species, in the last years. This enables comparison of strains from different ecological niches and can be used to define the functional potential in a bacterial population. It gives us a much better view of microbial genomics than can be gained from singular genomes which after all are just single representatives of a much more varied population.

Previously published pangenome tools often reduce the information to a presence/absence matrix of unconnected genes or generate massive hard to interpret output graphs. However, Panakeia includes synteny and structural information and presents it in a way that can readily be used for further analysis. Panakeia can be downloaded athttps://github.com/BioSina/Panakeia.
Human stem cell-based retina-on-chip as new translational model for validation of AAV retinal gene therapy vectors
Authors: Achberger Kevin , Cipriano Madalena , Düchs Matthias , Schön Christian , Michelfelder Stefan , Stierstorfer Birgit , Lamla Thorsten , Kauschke Stefan G. , Chuchuy Johanna , Roosz Julia , Mesch Lena , Cora Virginia , Pars Selin , Pashkovskaia Natalia , Corti Serena , Kleger Alexander , Kreuz Sebastian , Maier Udo , Liebau Stefan , Loskill Peter
Published: March 2021

Gene therapies using adeno-associated viruses (AAVs) are amongst the most promising strategies to treat or even cure hereditary and acquired retinal diseases. However, the development of new efficient AAV vectors is slow and costly, largely because of the lack of suitable non-clinical models. By faithfully recreating structure and function of human tissues, human induced pluripotent stem cell (iPSC)-derived retinal organoids could become an essential part of the test cascade addressing translational aspects. Organ-on-Chip (OoC) technology further provides the capability to recapitulate microphysiological tissue environments as well as a precise control over structural and temporal parameters. By employing our recently developed Retina-on-chip that merges organoid and OoC-technology, we analyzed the efficacy, kinetics and cell tropism of seven first and second generation AAV vectors. The presented data demonstrate the potential of iPSC-based OoC models as the next generation of screening platforms for future gene therapeutic studies.
Optimal BR signalling is required for adequate cell wall orientation in the Arabidopsis root meristem
Authors: Li Zhenni , Sela Ayala , Fridman Yulia , Höfte Herman , Savaldi-Goldstein Sigal , Wolf Sebastian
Published: March 2021

The plant steroid hormones brassinosteroids (BRs) regulate growth in part through altering the properties of the cell wall, the extracellular matrix of plant cells. Conversely, cell wall signalling connects the state of cell wall homeostasis to the BR receptor complex and modulates BR activity. Here we report that both pectin-triggered cell wall signalling and impaired BR signalling result in altered cell wall orientation in the Arabidopsis root meristem. BR-induced defects in the orientation of newly placed walls are associated with aberrant localization of the cortical division zone but with normal specification of its positioning. Tissue- specific perturbations of BR signalling revealed that the cellular malfunction is unrelated to previously described whole organ growth defects. Thus, tissue type separates the pleiotropic effects of cell wall/BR signals and highlights their importance during cell wall placement.
Intracellular Oxidative Stress Levels are Significantly Associated with the Green Autofluorescence Intensity of Buthionine Sulfoximine-Treated B16-F10 Cells
Authors: Tang Wanzhi , Ying Weihai
Published: March 2021

Since oxidative stress is a critical common pathological factor of numerous diseases, it is critical to find biomarkers for non-invasive evaluations of the levels of oxidative stress in the body. Our previous studies have indicated that epidermal green autofluorescence (AF) is a novel biomarker of this type: The oxidative stress inducer buthionine sulfoximine (BSO) can dose-dependently increase the epidermal green AF of mice, with BSO doses being significantly associated with the AF intensity. However, it is necessary to use skin cell cultures to investigate the mechanisms underlying the relationships between BSO and the green AF intensity. In our current study we found that BSO concentration-dependently increased the green AF intensity of B16-F10 cells a skin cell line, with BSO concentrations being significantly associated with the AF intensity. BSO also concentration-dependently increased the intracellular DCF signals an index of ROS levels. The green AF intensity of the cells was also significantly associated with the intracellular ROS levels. Moreover, we found that the green AF intensity was significantly associated with the cell death induced by BSO. Collectively, our study has provided first evidence indicating that the green AF intensity of skin cells is significantly associated with both intracellular ROS levels and cell death of the skin cells exposed to oxidative stress, which has indicated that green AF is a novel biomarker for both oxidative stress and cell death.
Multitaper Estimates of Phase-Amplitude Coupling
Authors: Lepage Kyle Q. , Fleming Cavan N. , Witcher Mark , Vijayan Sujith
Published: March 2021

Phase-amplitude coupling (PAC) is the association of the amplitude of a high-frequency oscillation with the phase of a low-frequency oscillation. In neuroscience, this relationship provides a mechanism by which neural activity might be coordinated between distant regions. The dangers and pitfalls of assessing phase-amplitude coupling with existing statistical measures have been well-documented. The limitations of these measures include: (i) response to non-oscillatory, high-frequency, broad-band activity, (ii) response to high-frequency components of the low-frequency oscillation, (iii) adhoc selection of analysis frequency-intervals, and (iv) reliance upon data shuffling to assess statistical significance. In this work, a multitaper phase-amplitude coupling estimator is proposed that addresses issues (i)-(iv) above. Specifically, issue (i) is addressed by replacing the analytic signal envelope estimator computed using the Hilbert transform with a multitaper estimator that down-weights non-sinusoidal activity using a classical, multitaper super-resolution technique. Issue (ii) is addressed by replacing coherence between the low-frequency and high-frequency components in a standard PAC estimator with multitaper partial coherence, while issue (iii) is addressed with a physical argument regarding meaningful neural oscillation. Finally, asymptotic statistical assessment of the multitaper estimator is introduced to address issue (iv).
Leveraging joint mechanics simplifies the neural control of movement
Authors: Ludvig Daniel , Whitmore Mariah W. , Perreault Eric J.
Published: March 2021

Behaviors we perform every day, such as manipulating an object or walking, require precise control of interaction forces between our bodies and the environment. These forces are generated by active muscle contractions, specified by the nervous system, and by joint mechanics, determined by the intrinsic properties of the musculoskeletal system. Depending on behavioral goals, joint mechanics might simplify or complicate control of movement by the nervous system. However, whether humans can exploit joint mechanics to simplify neural control remains unclear. Here we evaluated if leveraging joint mechanics can simplify neural control by comparing performance in three tasks that required subjects to generate specified torques about the ankle during imposed sinusoidal movements; only one task required torques that could be generated by leveraging the intrinsic mechanics of the joint. We developed a novel approach that used continuous estimates of impedance, a quantitative description of joint mechanics, and measures of muscle activity to determine the mechanical and neural contributions to the net ankle torque generated in each motor task. We found that the torque resulting from changes in neural control was reduced when ankle impedance was consistent with the task being performed, resulting in a task that required less muscular effort. Subjects perceived this task to be easier than those that were not consistent with the impedance of the ankle and were able to perform it with the highest level of consistency. These results demonstrate that leveraging the mechanical properties of a joint can simplify task completion and improve performance.

KEY POINTS

Interacting with our environment requires production of interaction forces, which are generated by muscle contractions, specified by the nervous system, and by joint mechanics, determined by the intrinsic properties of the musculoskeletal system.

We assessed whether leveraging joint mechanics can simplify neural control by having subjects complete 3 tasks, only one of which could be accomplished by leveraging joint mechanics.

We found that subjects reduced their muscular effort, perceived the task to be easier and completed the task more consistently when the mechanics of the ankle were consistent with the task.

These results highlight the importance of considering limb mechanics when interpreting measures of neural control related to movement and may benefit the design of mechanical interfaces that optimize human performance.
On the capacity of putative plant odorant-binding proteins to bind volatile plant isoprenoids
Authors: Giordano Deborah , Facchiano Angelo , D’Auria Sabato , Loreto Francesco
Published: March 2021

Plants use odors not only to recruit other organisms for symbioses, but to ‘talk’ to each other. Volatile organic compounds (VOCs) from “emitting” plants inform the “receiving” (listening) plants of impending stresses or simply of their presence. However, the receptors that allow receivers to perceive the volatile cue are elusive. Most likely, plants (as animals) have odorant bind proteins (OBPs), and in fact few OBPs are known to bind “stress-induced” plant VOCs. We investigated whether OBPs may bind volatile constitutive and stress-induced isoprenoids, the most emitted plant VOCs, with well-established roles in plant communication. First, we performed a data base search that generated a list of candidate plant OBPs. Second, we investigatedin silicothe ability of the identified candidate plant OBPs to bind VOCs by molecular simulation experiments. Our results show that monoterpenes can bind the same OBPs that were described to bind other stress-induced VOCs. Whereas, the constitutive hemiterpene isoprene does not bind any investigated OBP and may not have an info-chemical role. We conclude that, as for animal, plant OBPs may bind different VOCs. Despite being generalist and not specialized, plant OBPs may play an important role in allowing plants to eavesdrop messages sent by neighboring plants.