bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody binding and ACE2 binding inhibition is significantly reduced for the Omicron variant compared to all other variants of concern
Authors: Junker Daniel , Becker Matthias , Wagner Teresa R. , Kaiser Philipp D. , Maier Sandra , Grimm Tanja M. , Griesbaum Johanna , Marsall Patrick , Gruber Jens , Traenkle Bjoern , Heinzel Constanze , Pinilla Yudi T. , Held Jana , Fendel Rolf , Kreidenweiss Andrea , Nelde Annika , Maringer Yacine , Schroeder Sarah , Walz Juliane S. , Althaus Karina , Uzun Gunalp , Mikus Marco , Bakchoul Tamam , Schenke-Layland Katja , Bunk Stefanie , Haeberle Helene , Göpel Siri , Bitzer Michael , Renk Hanna , Remppis Jonathan , Engel Corinna , Franz Axel R. , Harries Manuela , Kessel Barbora , Strengert Monika , Krause Gerard , Zeck Anne , Rothbauer Ulrich , Dulovic Alex , Schneiderhan-Marra Nicole
Published: January 2022

The rapid emergence of the Omicron variant and its large number of mutations has led to its classification as a variant of concern (VOC) by the WHO(1). Initial studies on the neutralizing response towards this variant within convalescent and vaccinated individuals have identified substantial reductions(2-8). However many of these sample sets used in these studies were either small, uniform in nature, or were compared only to wild-type (WT) or, at most, a few other VOC. Here, we assessed IgG binding, (Angiotensin-Converting Enzyme 2) ACE2 binding inhibition, and antibody binding dynamics for the omicron variant compared to all other VOC and variants of interest (VOI)(9), in a large cohort of infected, vaccinated, and infected and then vaccinated individuals. While omicron was capable of binding to ACE2 efficiently, antibodies elicited by infection or immunization showed reduced IgG binding and ACE2 binding inhibition compared to WT and all VOC. Among vaccinated samples, antibody binding responses towards omicron were only improved following administration of a third dose. Overall, our results identify that omicron can still bind ACE2 while pre-existing antibodies can bind omicron. The extent of the mutations appear to inhibit the development of a neutralizing response, and as a result, omicron remains capable of evading immune control.
Retinal fundus photographs capture hemoglobin loss after blood donation
Authors: Mitani Akinori , Traynis Ilana , Singh Preeti , Corrado Greg S. , Webster Dale R. , Peng Lily H. , Varadarajan Avinash V. , Liu Yun , Hammel Naama
Published: January 2022

Recently it was shown that blood hemoglobin concentration could be predicted from retinal fundus photographs by deep learning models. However, it is unclear whether the models were quantifying current blood hemoglobin level, or estimating based on subjects’ pretest probability of having anemia. Here, we conducted an observational study with 14 volunteers who donated blood at an on site blood drive held by the local blood center (ie, at which time approximately 10% of their blood was removed). When the deep learning model was applied to retinal fundus photographs taken before and after blood donation, it detected a decrease in blood hemoglobin concentration within each subject at 2-3 days after donation, suggesting that the model was quantifying subacute hemoglobin changes instead of predicting subjects’ risk. Additional randomized or controlled studies can further validate this finding.
From Delta to Omicron: analysing the SARS-CoV-2 epidemic in France using variant-specific screening tests (September 1 to December 18, 2021)
Authors: Sofonea Mircea T. , Roquebert Bénédicte , Foulongne Vincent , Verdurme Laura , Trombert-Paolantoni Sabine , Roussel Mathilde , Haim-Boukobza Stéphanie , Alizon Samuel
Published: January 2022

We analysed 131,478 SARS-CoV-2 variant screening tests performed in France from September 1st to December 18, 2021. Tests consistent with the presence of the Omicron variant exhibit significantly higher cycle threshold Ct values, which could indicate lower amounts of virus genetic material. We estimate that the transmission advantage of the Omicron variant over the Delta variant is +105% (95% confidence interval: 96-114%). Based on these data, we use mechanistic mathematical modelling to explore scenarios for early 2022.
Social isolation and psychological distress among southern US college students in the era of COVID-19
Authors: Giovenco Danielle , Shook-Sa Bonnie E , Hutson Bryant , Buchanan Laurie , Fisher Edwin B , Pettifor Audrey
Published: January 2022

Objective

To examine the prevalence of psychological distress and its association with social isolation among University of North Carolina Chapel Hill (UNC-CH) students.

Methods

A cross-sectional survey was emailed to all students in June 2020. Students reported self-isolating none, some, most, or all of the time and were screened for clinically significant symptoms of depression (CSSD). Data were weighted to the UNC-CH population.

Results

7,012 students completed surveys-64% reported self-isolating most or all of the time and 64% reported CSSD. Compared to those self-isolating none of the time, students self-isolating some of the time were 1.78 (95% CI 1.37-2.30) times as likely to report CSSD, and students self-isolating most and all of the time were 2.12 (95% CI 1.64-2.74) and 2.27 (95% CI 1.75-2.94) times as likely to report CSSD, respectively.

Conclusions

Universities should prioritize student mental health and prepare support services to mitigate mental health consequences of the pandemic.
Inter-individual deep image reconstruction
Authors: Ho Jun Kai , Horikawa Tomoyasu , Majima Kei , Cheng Fan , Kamitani Yukiyasu
Published: January 2022

The sensory cortex is characterized by general organizational principles such as topography and hierarchy. However, measured brain activity given identical input exhibits substantially different patterns across individuals. Although anatomical and functional alignment methods have been proposed in functional magnetic resonance imaging (fMRI) studies, it remains unclear whether and how hierarchical and fine-grained representations can be converted between individuals while preserving the encoded perceptual content. In this study, we trained a method of functional alignment called neural code converter that predicts a target subject’s brain activity pattern from a source subject given the same stimulus, and analyzed the converted patterns by decoding hierarchical visual features and reconstructing perceived images. The converters were trained on fMRI responses to identical sets of natural images presented to pairs of individuals, using the voxels on the visual cortex that covers from V1 through the ventral object areas without explicit labels of the visual areas. We decoded the converted brain activity patterns into the hierarchical visual features of a deep neural network using decoders pre-trained on the target subject and then reconstructed images via the decoded features. Without explicit information about the visual cortical hierarchy, the converters automatically learned the correspondence between visual areas of the same levels. Deep neural network feature decoding at each layer showed higher decoding accuracies from corresponding levels of visual areas, indicating that hierarchical representations were preserved after conversion. The visual images were reconstructed with recognizable silhouettes of objects even with relatively small numbers of data for converter training. The decoders trained on pooled data from multiple individuals through conversions lead to a slight improvement over those trained on a single individual. These results demonstrate that the hierarchical and fine-grained representation can be converted by functional alignment, while preserving sufficient visual information to enable inter-individual visual image reconstruction.

Highlights

● Neural code converters convert brain activity patterns across individuals with moderate conversion accuracy and learn reasonable visual area correspondences at the same level between individuals.

● The converted brain activity patterns can be decoded into hierarchical DNN features to reconstruct visual images, even though the converter is trained on a small number of data samples.

● The information of hierarchical and fine-scale visual features that enable visual image reconstruction are preserved after functional alignment.
Testing the state-dependent model of subsecond time perception against experimental evidence
Authors: Ravichandran-Schmidt Pirathitha , Hass Joachim
Published: January 2022

Coordinated movements, speech, and other actions are impossible without precise timing. Computational models of interval timing are expected to provide key insights into the underlying mechanisms of timing, which are currently largely unknown. So far, existing models have only been partially replicating key experimental observations, such as the linear psychophysical law, the linear increase of the standard deviation (the scalar property or Weber’s law), and the modulation of subjective duration via dopamine. Here, we incorporate the state-dependent model for subsecond timing as proposed by Buonomano (2000) into a strongly data-driven computational network model of PFC We show that this model variant, the state-dependent PFC model, successfully encodes time up to 750 milliseconds and reproduces all key experimental observations mentioned above, including many of its details. Investigating the underlying mechanisms, we find that the representations of different intervals are based on the natural heterogeneity in the parameters of the network, leading to stereotypic responses of subsets of neurons. Furthermore, we propose a theory for the mechanism underlying subsecond timing in this model based on correlation and ablation analyses as well as mathematical analyses explaining the emergence of the scalar property and Vierordt law. The state-dependent PFC model proposed here constitutes the first data-driven model of subsecond timing in the range of hundreds of milliseconds that has been thoroughly tested against a variety of experimental data, providing an ideal starting point for further investigations of subsecond timing.

Highlights

The state-dependent model of time perception also encodes durations in the subsecond range when embedded into a data-driven network model of the prefrontal cortex.

The model reproduces three key experimental findings of time perception: the linear psychophysical law, the scalar property (Weber’s law) and dopaminergic modulation of subjective durations.

Many details of experimental observations can be reproduced and explained by the model without specific parameter tuning.

A new theory for the emergence of Weber’s law and Vierordt’s law (overestimation of short durations and underestimation of long durations) is provided.

The current variant of the state-dependent model is the first model of time perception to be thoroughly tested against a wide range of experimental evidence and can now be considered to be experimentally validated.
P2RX7 inhibition reduces breast cancer induced osteolytic lesions - implications for bone metastasis
Authors: Shah Karan M. , Tattersall Luke , Hussain Aleana , Macfarlane Sarah C. , Williamson Alexander , Acosta-Martin Adelina E. , Erler Janine T. , Ottewell Penelope D. , Gartland Alison
Published: January 2022

Breast cancer metastasis to bone is a major contributor to morbidity and mortality in patients and remains an unmet clinical need. Purinergic signalling via the P2X7 receptor (P2RX7) in the primary tumour microenvironment is associated with progression of several cancers. It has also now become evident that intra-tumoural hypoxia facilitates cancer metastasis and reduces patient survival. In this study, we present data suggesting that hypoxia regulates the expression of P2RX7 in the primary tumour microenvironment; and importantly, inhibition with a selective antagonist (10mg/kg A740003) increased cancer cell death via apoptosis in a E0771/C57BL-6J syngeneic murine model. Furthermore, micro-computed tomography demonstrated reduced number of osteolytic lesions and lesion area following P2RX7 inhibition in absence of overt metastases by decreasing osteoclast numbers. We also demonstrate that activation of P2RX7 plays a role in the secretion of extracellular vesicles (EVs) from breast cancer cells. Mass-spectrometric analyses showed a distinct protein signature for EVs derived from hypoxic compared with normoxic cancer cells which elicit specific responses in bone cells that are associated with pre-metastatic niche formation. Thus, inhibiting P2RX7 provides a novel opportunity to preferentially target the hypoxic breast cancer cells preventing tumour progression and subsequent metastasis to bone
Northward Expansion ofAmblyomma americanum(Acari: Ixodidae) into Southern Michigan
Authors: Fowler Peter D. , Nguyentran S. , Quatroche L. , Porter M.L. , Kobbekaduwa V. , Tippin S. , Miller Guy , Dinh E. , Foster E. , Tsao J.I.
Published: January 2022

Amblyomma americanum(Linnaeus) (Acari: Ixodidae) (lone star tick) is an aggressive, generalist parasite that vectors numerous important human and animal pathogens. In recent decades its geographic range has expanded northwards from endemic regions in the southeastern and southcentral US. In 2019 five questingA. americanumcomprising two life stages were detected at one site in Berrien County, in southwestern Michigan, satisfying one CDC criterium for an established population for the first time in the state. To better characterize the northern extent of emergingA. americanum, we conducted active surveillance (i.e., drag sampling) in summer 2020 throughout Michigan’s southern counties and detected one adultA. americanumfrom each of six widespread sites, including where they had been detected in 2019. A larger established population was identified at another site in Berrien County, which yielded 691A. americanumcomprising three life stages. Questing tick phenologies at this site were similar to that reported for other regions. Statewide surveillance in 2021 revealed noA. americanumoutside of Berrien County, but establishment criteria were met again at the two sites where established populations were first detected respectively in 2019 and 2020. These observations may represent the initial successful invasion ofA. americanuminto Michigan. Data from passive (1999-2020) and active surveillance (2004-2021) efforts, including a domestic animal sentinel program (2015-2018), are reported to provide context for this nascent invasion. Continued active surveillance is needed to help inform the public, medical professionals, and public health officials of the health risks associated with this vector.
The TOG protein Stu2 is regulated by acetylation
Authors: Greenlee Matt , Witt Braden , Sabo Jeremy , Morris Savannah , Miller Rita K.
Published: January 2022

Stu2 in S. cerevisiae is a member of the XMAP215/Dis1/Alp14/Msps/CKAP5/ch-TOG family of MAPs and has multiple functions in controlling microtubules, including microtubule polymerization, microtubule depolymerization, linking chromosomes to the kinetochore, and assembly of γ-TuSCs at the SPB. Whereas phosphorylation has been shown to be critical for Stu2 localization at the kinetochore, other regulatory mechanisms that control Stu2 function are still poorly understood. Here, we show that a novel form of Stu2 regulation occurs through the acetylation of three lysine residues at K252, K469, and K870, which are located in three distinct domains of Stu2. Alteration of acetylation through acetyl-mimetic and acetyl-blocking mutations did not impact the essential function of Stu2. Instead, these mutations lead to both positive and negative changes in chromosome stability, as well as changes in resistance to the microtubule depolymerization drug, benomyl. In agreement with our in silico modeling, several acetylation-mimetic mutants displayed increased interactions with γ-tubulin. Taken together, these data suggest that Stu2 acetylation can govern multiple Stu2 functions in both a positive and negative manner, including chromosome stability and interactions at the SPB.
Analyzing the relationship between distracted driving and eye movement using multimodal data collected during car driving
Authors: Uraki Daigo , Tanioka Kensuke , Hiwa Satoru , Furutani Hiroshi , Hiroyasu Tomoyuki
Published: January 2022

Human error is the leading cause of traffic accidents and originates from the distraction caused by various factors, such as the driver’s physical condition and mental state. One of the significant factors causing driver distraction is the presence of stress. In a previous study, multiple stressors were used to examine distraction while driving. Multiple stressors were given to the driver and the corresponding driver biometric data were obtained, and a multimodal dataset was published thereafter. In this study, we reiterate the results of existing studies and investigated the relationship between gaze variability while driving and stressor intervention, which has not yet been examined. We also examined whether biometric and vehicle information can estimate the presence or absence of secondary tasks during driving.
PlasmidMaker: a Versatile, Automated, and High Throughput End-to-End Platform for Plasmid Construction
Authors: Enghiad Behnam , Xue Pu , Singh Nilmani , Boob Aashutosh , Shi Chengyou , Petrov Vassily Andrew , Liu Roy , Peri Siddhartha Suryanarayana , Lane Stephan Thomas , Gaither Emily Danielle , Zhao Huimin
Published: January 2022

Plasmids are used extensively in basic and applied biology. However, design and construction of plasmids, specifically the ones carrying complex genetic information, remains one of the most time-consuming, labor-intensive, and rate-limiting steps in performing sophisticated biological experiments. Here, we report the development of a versatile, robust, automated end-to-end platform named PlasmidMaker that allows error-free construction of plasmids with virtually any sequences in a high-throughput manner. This platform consists of a most versatile DNA assembly method using Pyrococcus furiosus Argonaute (PfAgo)-based artificial restriction enzymes, a user-friendly frontend for plasmid design, and a backend that streamlines the workflow and integration with a robotic system. As a proof of concept, we used this platform to generate 101 plasmids from six different species ranging from 5 to 18 kb in size from up to 11 DNA fragments within 3 days. PlasmidMaker should greatly expand the potential of synthetic biology.
Single-cell transcriptome reveals the redifferentiation trajectories of the early stage of de novo shoot regeneration in Arabidopsis thaliana
Authors: Liu Guangyu , Li Jie , Li Ji-Ming , Chen Zhiyong , Yuan Peisi , Chen Ruiying , Yin Ruilian , Liao Zhiting , Li Xinyue , Gu Ying , Sun Hai-Xi , Xia Keke
Published: January 2022

De novo shoot regeneration from a callus plays a crucial role in both plant biotechnology and the fundamental research of plant cell totipotency. Recent studies have revealed many regulatory factors involved in this developmental process. However. our knowledge of the cell heterogeneity and cell fate transition during de novo shoot regeneration is still limited. Here, we performed time-series single-cell transcriptome experiments to reveal the cell heterogeneity and redifferentiation trajectories during the early stage of de novo shoot regeneration. Based on the single-cell transcriptome data of 35,669 cells at five-time points, we successfully determined seven major cell populations in this developmental process and reconstructed the redifferentiation trajectories. We found that all cell populations resembled root identities and undergone gradual cell-fate transitions. In detail, the totipotent callus cells differentiated into pluripotent QC-like cells and then gradually developed into less differentiated cells that have multiple root-like cell identities, such as pericycle-like cells. According to the reconstructed redifferentiation trajectories, we discovered that the canonical regeneration-related genes were dynamically expressed at certain stages of the redifferentiation process. Moreover, we also explored potential transcription factors and regulatory networks that might be involved in this process. The transcription factors detected at the initial stage, QC-like cells, and the end stage provided a valuable resource for future functional verifications. Overall, this dataset offers a unique glimpse into the early stages of de novo shoot regeneration, providing a foundation for a comprehensive analysis of the mechanism of de novo shoot regeneration.
Efficient simulation of 3D reaction-diffusion in models of neurons and networks
Authors: McDougal Robert A. , Conte Cameron , Eggleston Lia , Newton Adam J.H. , Galijasevic Hana
Published: January 2022

Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma.

We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON’s 1D mechanisms for ion channels, synapses, etc. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.
Temporal control of the integrated stress response by a stochastic molecular switch
Authors: Klein Philipp , Kallenberger Stefan M. , Roth Hanna , Roth Karsten , Ly-Hartig Thi Bach Nga , Magg Vera , Aleš Janez , Talemi Soheil Rastgou , Qiang Yu , Wolf Steffen , Oleksiuk Olga , Kurilov Roma , Di Ventura Barbara , Bartenschlager Ralf , Eils Roland , Rohr Karl , Hamprecht Fred A. , Höfer Thomas , Fackler Oliver T. , Stoecklin Georg , Ruggieri Alessia
Published: January 2022

Stress granules (SGs) are formed in the cytosol as an acute response to environmental cues and activation of the integrated stress response (ISR), a central signaling pathway controlling protein synthesis. Using chronic virus infection as stress model, we previously uncovered a unique temporal control of the ISR resulting in recurrent phases of SG assembly and disassembly. Here, we elucidate the molecular network generating this fluctuating stress response, by integrating quantitative experiments with mathematical modeling, and find that the ISR operates as a stochastic switch. Key elements controlling this switch are the cooperative activation of the stress-sensing kinase PKR, the ultrasensitive response of SG formation to the phosphorylation of the translation initiation factor eIF2α, and negative feedback via GADD34, a stress-induced subunit of protein phosphatase 1. We identify GADD34 mRNA levels as the molecular memory of the ISR that plays a central role in cell adaptation to acute and chronic stress.
Synthetic Data Resource and Benchmarks for Time Cell Analysis and Detection Algorithms
Authors: Ananthamurthy Kambadur Gundu , Bhalla Upinder S
Published: January 2022

Hippocampal CA1 cells take part in reliable, time-locked activity sequences in tasks that involve an association between temporally separated stimuli, in a manner that tiles the interval between the stimuli. Such cells have been termed time cells. Here we adopt a first-principles approach to comparing diverse analysis and detection algorithms for identifying time cells. We generated synthetic activity datasets using calcium signals recordedin vivofrom the mouse hippocampus using 2-Photon imaging, as template response waveforms. We assigned known, ground truth values to perturbations applied to perfect activity signals, including noise, calcium event width, timing imprecision, hit-trial ratio and background (untuned) activity. We tested a range of published and new algorithms and their variants on this dataset. We find that most algorithms correctly classify over 80% of cells, but have different balances between true and false positives, and different sensitivity to the five categories of perturbation. Reassuringly, most methods are reasonably robust to perturbations, including background activity, and show good concordance in classification of time cells. The same algorithms were also used to analyse and identify time cells in experimental physiology datasets recordedin vivoand most show good concordance.

Significance Statement

Numerous approaches have been developed to analyze time cells and neuronal activity sequences, but it is not clear if their classifications match, nor how sensitive they are to various sources of data variability. We provide two main contributions to address this: 1) A resource to generate ground truth labelled synthetic 2-P Calcium activity data with defined distributions for confounds such as noise and background activity, and 2) a survey of several methods for analyzing time-cell data using our synthetic data as ground truth. As a further resource, we provide a library of efficient C++ implementations of several algorithms with a Python interface. The synthetic dataset and its generation code are useful for profiling future methods, testing analysis toolchains, and as input to computational and experimental models of sequence detection.
Dealing with the promise of metabarcoding in mega-event biomonitoring: EXPO2015 unedited data
Authors: Agostinetto Giulia , Bruno Antonia , Sandionigi Anna , Brusati Alberto , Manzari Caterina , Chiodi Alice , Siani Eleonora , Borruso Luigimaria , Galimberti Andrea , Pesole Graziano , Labra Massimo , Casiraghi Maurizio
Published: January 2022

As human activities on our planet persist, causing widespread and irreversible environmental degradation, the need to biomonitor ecosystems has never been more pressing. These circumstances have required a renewal in monitoring techniques, encouraged by necessity to develop more rapid and accurate tools which will support timely observations of ecosystem structure and function. The World Exposition (from now ‘EXPO2015’) hosted in Milan from May to October 2015 was a global event that could be categorized as a mega-event, which can be defined as an acute environmental stressor, possibly generating biodiversity alteration and disturbance.

During the six months of EXPO2015, exhibitors from more than 135 countries and 22 million visitors insisted on a 1.1 million square meters area. Faced with such a massive event, we explore the potential of DNA metabarcoding using three molecular markers to improve the understanding of anthropogenic impacts in the area, both considering air and water monitoring. Furthermore, we explore the effectiveness of the taxonomy assignment phase considering different taxonomic levels of analysis and the use of data mining approaches to predict sample origin. Unless the degree of taxa identification still remains open, our results showed that DNA metabarcoding is a powerful genomic-based tool to monitor biodiversity at the microscale, allowing us to capture exact fingerprints of specific event sites and to explore in a comprehensive manner the eukaryotic community alteration. With this work, we aim to disentangle and overcome the crucial issues related to the generalization of DNA metabarcoding in order to support future applications.
Cell-based screen identifies human type I interferon-stimulated regulators ofToxoplasma gondiiInfection
Authors: Gossner Anton , Raper Anna , Hassan Musa A.
Published: January 2022

Macrophages activated with interferons (IFNs) respond with transcriptional changes that enhance clearance of intracellular pathogens such asToxoplasma, a ubiquitous apicomplexan parasite that infects more than a billion people worldwide. Although IFNs generally inhibitToxoplasma, the parasite can also induce components of the host IFN signalling pathway to enhance survival in host cells. Compared to the type II IFN gamma (IFNγ), the role of type I IFNs in macrophage response toToxoplasmais relatively not well characterized. Here, using fluorescentToxoplasmaand a CRISPR/Cas9 knockout library that only targets interferon-stimulated genes (ISGs), we adapted a loss-of-function flow cytometry-based approach to systematically identify type I ISGs that controlToxoplasmagrowth in THP-1 cells, a human macrophage cell line. The system enabled the rapid screening of more than 1900 ISGs for type I (IFNα)-induced inhibitors and enhancers ofToxoplasmagrowth in THP-1 cells. We identified 26 genes that are associated withToxoplasmagrowth arrest out of which we confirmedMAX, SNX5, F2RL2, andSSB, as potent IFNα-induced inhibitors ofToxoplasmain THP1 cells. These findings provide a genetic and experimental roadmap to elucidate type I IFN-induced cell-autonomous responses toToxoplasma.
COVID-19 disease progression according to initial symptoms. A telemedicine cohort study
Authors: Murillo-Villanueva Karla , Velázquez-Hernández Blanca , Jácome-Mondragón José A. , Cervantes-Llamas Judit J. , Talavera Juan O.
Published: January 2022

Objective

COVID-19 progression to severe or critical illness may be related to initial clinical presentation. Main objective was to identify initial symptoms related to highest risk of disease progression, in mild or moderate suspected or confirmed COVID-19 patients or in asymptomatic subjects in contact with a recently diagnosed patient.

Design and methods

Historic cohort study of Mexican patients with suspected or confirmed mild or moderate COVID-19 or asymptomatic subjects in recent contact with positive patients. They sought medical attention in “Centro Médico ABC” or claimed for remote attention, and daily telemedicine follow up until recovery or illness progression, from April 17th to October 08th 2020. Data excerpted for analysis were sex, age, body mass index, comorbidities, and signs, and symptoms presented in first day of disease manifestations and during follow up. We used logistic regression to identify initial symptoms associated with progression disease and through a conjunctive consolidation analysis a symptom index was created.

Results

120 of 1635 patients (7.2%) had clinical progression disease. By logistic regression we found as initial symptoms related to progression: fever OR 3 (1.89-4.77, p<0.001), cough OR 2.34 (1.56-3.52, p<0.001), myalgias or arthralgias OR 1.69 (1.09-2.63, p=0.018), and fatigue OR 1.65 (1.08-2.53, p=0.019). Conjunctive consolidation was processed with the previous symptoms, and a 3 groups score resulted C-19PAIS Index: 1) Fever with cough or fever with fatigue, with a probability of progression disease of 29% (31/106 patients), 2) Fever or cough or fatigue or cough with fatigue, 10.7% (66/615 patients) and 3) No fever, no cough, no fatigue, 2% (23/914).

Conclusions

Initial symptoms predict clinical progression in COVID-19 patients.
Comparative plant transcriptome profiling of Arabidopsis and Camelina infested withMyzus persicaeaphids acquiring circulative and non-circulative viruses reveals virus- and plant-specific alterations relevant to aphid feeding behavior and transmission
Authors: Chesnais Quentin , Golyaev Victor , Velt Amandine , Rustenholz Camille , Brault Véronique , Pooggin Mikhail , Drucker Martin
Published: January 2022

Background

Evidence accumulates that plant viruses alter host-plant traits in ways that modify their insect vectors’ behavior. These alterations often enhance virus transmission, which has led to the hypothesis that these effects are manipulations caused by viral adaptation. However, the genetic basis of these indirect, plant-mediated effects on vectors and their dependence on the plant host and the mode of virus transmission is hardly known.

Results

Transcriptome profiling ofArabidopsis thalianaandCamelina sativaplants infected with turnip yellows virus (TuYV) or cauliflower mosaic virus (CaMV) and infested with the common aphid vectorMyzus persicaerevealed strong virus- and host-specific differences in the gene expression patterns. CaMV infection caused more severe effects on the phenotype of both plant hosts than did TuYV infection, and the severity of symptoms correlated strongly with the proportion of differentially expressed genes, especially photosynthesis genes. Accordingly, CaMV infection modified aphid behavior and fecundity stronger than did infection with TuYV.

Conclusions

Overall, infection with CaMV – relying on the non-circulative transmission mode – tends to have effects on metabolic pathways with strong potential implications for insect-vector / plant-host interactions (e.g. photosynthesis, jasmonic acid, ethylene and glucosinolate biosynthetic processes), while TuYV – using the circulative transmission mode – alters these pathways only weakly. These virus-induced deregulations of genes that are related to plant physiology and defense responses might impact aphid probing and feeding behavior on both infected host plants, with potentially distinct effects on virus transmission.
hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function
Authors: Majd Homa , Samuel Ryan M , Ramirez Jonathan T , Kalantari Ali , Barber Kevin , Ghazizadeh Zaniar , Chemel Angeline K , Cesiulis Andrius , Richter Mikayla N , Das Subhamoy , Keefe Matthew G , Wang Jeffrey , Shiv Rahul K , McCann Conor J , Bhat Samyukta , Khoroshkin Matvei , Yu Johnny , Nowakowski Tomasz J , Goodarzi Hani , Thapar Nikhil , Kaltschmidt Julia A , Fattahi Faranak
Published: January 2022

The enteric nervous system (ENS) plays a central role in gut physiology and mediating the crosstalk between the gastrointestinal (GI) tract and other organs. The human ENS has remained elusive, highlighting the need for an in vitro modeling and mapping blueprint. Here we map out the developmental and functional features of the human ENS, by establishing robust and scalable 2D ENS cultures and 3D enteric ganglioids from human pluripotent stem cells (hPSCs). These models recapitulate the remarkable neuronal and glial diversity found in primary tissue and enable comprehensive molecular analyses that uncover functional and developmental relationships within these lineages. As a salient example of the power of this system, we performed in-depth characterization of enteric nitrergic neurons (NO neurons) which are implicated in a wide range of GI motility disorders. We conducted an unbiased screen and identified drug candidates that modulate the activity of NO neurons and demonstrated their potential in promoting motility in mouse colonic tissue ex vivo. We established a high-throughput strategy to define the developmental programs involved in NO neuron specification and discovered that PDGFR inhibition boosts the induction of NO neurons in enteric ganglioids. Transplantation of these ganglioids in the colon of NO neuron-deficient mice results in extensive tissue engraftment, providing a xenograft model for the study of human ENS in vivo and the development of cell-based therapies for neurodegenerative GI disorders. These studies provide a framework for deciphering fundamental features of the human ENS and designing effective strategies to treat enteric neuropathies.
New genomic signals underlying the emergence of human proto-genes
Authors: Grandchamp Anna , Berk Katrin , Dohmen Elias , Bornberg-Bauer Erich
Published: January 2022

De novo genes are novel genes which emerge from non-coding DNA. Until now, little is known about de novo genes properties, correlated to their age and mechanisms of emergence. In this study, we investigate four properties: introns, upstream regulatory motifs, 5’ UTRs and protein domains, in 23135 human proto-genes. We found that proto-genes contain introns, whose number and position correlates with the genomic position of proto-gene emergence. The origin of these introns is debated, as our result suggest that 41% proto-genes might have captured existing introns, as well as the fact that 13.7% of them do not splice the ORF. We show that proto-genes which emerged via overprinting tend to be more enriched in core promotor motifs, while intergenic and intronic ones are more enriched in enhancers, even if the motif TATA is most expressed upstream these genes. Intergenic and intronic 5’ UTRs of protogenes have a lower potential to stabilise mRNA structures than exonic proto-genes and established human genes. Finally, we confirm that proto-genes gain new putative domains with age. Overall, we find that regulatory motifs inducing transcription and translation of previously non-coding sequences may facilitate proto-gene emergence. Our paper demonstrates that introns, 5’UTRs, and domains have specific properties in proto-genes. We also show the importance of studying proto-genes in relation to their genomic position, as it strongly impacts these properties.
Maternal cytokine response after SARS-CoV-2 infection during pregnancy
Authors: Gigase Frederieke A.J. , Molenaar Nina M. , Missall Roy D. , Rommel Anna-Sophie , Lieb Whitney , Ibroci Erona , Ohrn Sophie , Lynch Jezelle , Krammer Florian , Brody Rachel , Jessel Rebecca H. , Sperling Rhoda S. , Lesseur Corina , Callipari Francesco , Galang Romeo R. , Snead Margaret C. , Janevic Teresa , Stone Joanne , Howell Elizabeth A. , Chen Jia , Pop Victor J.M. , Dolan Siobhan M. , Bergink Veerle , De Witte Lotje D.
Published: January 2022

Objective: Dysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels.
Study design: We conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured.
Results: Individual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy.
Conclusion: Our findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy.
The tetraspanin TSPAN5 regulates AMPARs exocytosis by interacting with the AP-4 complex
Authors: Edoardo Moretto , Anna Longatti , Miozzo Federico , Bonnet Caroline , Coussen Francoise , Jaudon Fanny , Cingolani Lorenzo A. , Maria Passafaro
Published: January 2022

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses in both basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 specifically promotes exocytosis of newly synthesised GluA2-containing AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with AP-4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. In addition, it provides a possible mechanism for the intellectual disability symptoms that occur in AP-4 deficiency syndrome.
Reduced local mechanical stimuli in spaceflight diminishes osteocyte lacunar morphometry and spatial heterogeneity in mouse cortical bone
Authors: Coulombe Jennifer C. , Mullen Zachary A. , Weins Ashton M. , Fisher Liam E. , Lynch Maureen E. , Stodieck Louis S. , Ferguson Virginia. L
Published: January 2022

Three-dimensional (3D) imaging of osteocyte lacunae has recently substantiated the connection between lacunar shape and size, and osteocyte age, viability, and mechanotransduction. Yet it remains unclear why individual osteocytes reshape their lacunae and how networks of osteocytes change in response to local alterations in mechanical loads. We evaluated the effects of local mechanical stimuli on osteocyte lacunar morphometrics in tibial cortical bone from young female mice flown on the Space Shuttle for ∼13 days. We optimized scan parameters, using a laboratory-based submicrometer-resolution X-Ray Microscope, to achieve large ∼ 0.3 mm3 fields of view with sufficient resolution (≥ 0.3 μm) to visualize and measure thousands of lacunae per scan. Our novel approach avoids large measurement errors that are inherent in 2D and enables a facile 3D solution as compared to the lower resolution from benchtop micro-computed tomography (CT) systems or the cost and inaccessibility of synchrotron-based CT. Osteocyte lacunae were altered following microgravity exposure in a region-specific manner: more elongated (+7.0% Stretch) in predominately tensile-loaded bone as compared to those in compressively-loaded regions. In compressively-loaded bone, lacunae formed in microgravity were significantly larger (+6.9% Volume) than in the same region formed on Earth. We also evaluated lacunar heterogeneity (i.e., spatial autocorrelation of lacunar morphometric parameters) via kriging models. These statistical models demonstrated that heterogeneity varied with underlying spatial contributors, i.e. the local mechanical and biological environment. Yet in the absence of gravitational loading, osteocyte lacunae in newly formed bone were larger and were collectively more homogenous than in bone formed on Earth. Overall, this study shows that osteocyte reshape their lacunae in response to changes, or absence, in local mechanical stimuli and different biological environments. Additionally, spatial relationships among osteocytes are complex and necessitate evaluation in carefully selected regions of interest and of large cell populations.

GRAPHICAL ABSTRACT
Exploring the rules of chimeric antigen receptor phenotypic output using combinatorial signaling motif libraries and machine learning
Authors: Daniels K.G. , Wang S. , Simic M.S. , Bhargava H.K. , Capponi S. , Tonai Y. , Yu W. , Bianco S. , Lim W.A.
Published: January 2022

Chimeric antigen receptor (CAR) costimulatory domains steer the phenotypic output of therapeutic T cells. In most cases these domains are derived from native immune receptors, composed of signaling motif combinations selected by evolution. To explore if non-natural combinations of signaling motifs could drive novel cell fates of interest, we constructed a library of CARs containing ∼2,300 synthetic costimulatory domains, built from combinations of 13 peptide signaling motifs. The library produced CARs driving diverse fate outputs, which were sensitive to motif combinations and configurations. Neural networks trained to decode the combinatorial grammar of CAR signaling motifs allowed extraction of key design rules. For example, the non-native combination of TRAF- and PLCγ1-binding motifs was found to simultaneously enhance cytotoxicity and stemness, a clinically desirable phenotype associated with effective and durable tumor killing. The neural network accurately predicts that addition of PLCγ1-binding motifs improves this phenotype when combined with TRAF-binding motifs, but not when combined with other immune signaling motifs (e.g. PI3K-or Grb2-binding motifs). This work shows how libraries built from the minimal building blocks of signaling, combined with machine learning, can efficiently guide engineering of receptors with desired phenotypes.

Graphical Abstract
Understanding host response to infectious salmon anaemia virus in an Atlantic salmon cell line using single-cell RNA sequencing
Authors: Gervais Ophélie , Gratacap Remi , Papadopoulou Athina , Houston Ross D. , Hassan Musa A. , Robledo Diego
Published: January 2022

Background

Infectious Salmon Anaemia Virus (ISAV) is an Orthomixovirus that currently represents a large problem for salmonid aquaculture worldwide. Prevention and treatment methods are only partially effective. Genetic selection and genome engineering strategies have potential to develop ISAV resistant salmon stocks. However, this requires a detailed understanding of the genomic regulation of ISAV pathogenesis. Here, we used single cell RNA sequencing on a salmonid cell line to provide a high dimensional insight into the transcriptional landscape that underpin host-virus interactions during ISAV infection at the single cell level.

Results

Salmon head kidney 1 (SHK-1) cells were single-cell RNA sequenced before challenge, and at 24h, 48h, and 96h post-ISAV challenge. The results revealed marked changes in the host transcriptome at 48h and 96h post-infection, even in uninfected cells, potentially suggesting paracrine signalling. This paracrine activation of uninfected cells seemed to be unspecific, involving pathways such as mRNA sensing, ubiquitination or proteasome, and also the up-regulation of the mitochondrial ribosome genes. At 24h post infection, cells showed expression signatures consistent with viral entry, with up-regulation of genes such as PI3K, FAK or JNK. At 48h and 96h, infected cells showed a clear anti-viral response, characterised by the expression of IFNA2 or IRF2.

Conclusions

This study has increased our understanding of the cellular response of Atlantic salmon during ISAV infection, and revealed potential host-virus interactions at the cellular level. The results highlight the value of single-cell sequencing to characterise cell culture models of viral infection, and the results can be exploited in future functional studies to increase the resistance of Atlantic salmon to ISAV.
A gas migration law study of a large-scale 3D physical similarity simulation with an adaptive Kalman filter algorithm
Authors: Hao Yuyu , Li Shugang , Zhang Tianjun
Published: January 2022

Purpose

In this study, a physical similarity simulation plays a significant role in the study of crack evolution and the gas migration mechanism. A sensor is deployed inside a comparable artificial rock formation to assure the accuracy of the experiment results. During the building of the simulated rock formation, a huge volume of acidic gas is released, causing numerous sensor measurement mistakes. Additionally, the gas concentration estimation approach is subject to uncertainty because of the complex rock formation environment. As a result, the purpose of this study is to introduce an adaptive Kalman filter approach to reduce observation noise, increase the accuracy of the gas concentration estimation model and, finally, determine the gas migration law.

Design/methodology/approach

First, based on the process of gas floatation-diffusion and seepage, the gas migration model is established according to Fick’s second law, and a simplified modeling method using diffusion flux instead of gas concentration is presented. Second, an adaptive Kalman filter algorithm is introduced to establish a gas concentration estimation model, taking into account the model uncertainty and the unknown measurement noise. Finally, according to a large-scale physical similarity simulation platform, a thorough experiment about gas migration is carried out to extract gas concentration variation data with certain ventilation techniques and to create a gas chart of the time-changing trend.

Findings

This approach is used to determine the changing process of gas distribution for a certain ventilation mode. The results match the rock fissure distribution condition derived from the microseismic monitoring data, proving the effectiveness of the approach.

Originality/value

For the first time in large-scale three-dimensional physical similarity simulations, the adaptive Kalman filter data processing method based on the inverse Wishart probability density function is used to solve the problem of an inaccurate process and measurement noise, laying the groundwork for studying the gas migration law and determining the gas migration mechanism.