bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections
Authors: Kennedy Allison E. , Cook Laura , Breznik Jessica A. , Cowbrough Braeden , Wallace Jessica G. , Huynh Angela , Smith James W , Son Kiho , Stacey Hannah , Ang Jann , McGeer Alison , Coleman Brenda L. , Larché Maggie , Larché Mark , Hambly Nathan , Nair Parameswaran , Ask Kjetil , Miller Matthew S. , Bramson Jonathan , Levings Megan K. , Nazy Ishac , Svenningsen Sarah , Mukherjee Manali , Bowdish Dawn M. E. 
Published: September 2021

AbstractSurvivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n=22) compared to those that had recovered from other mild respiratory infections (n=11). Individuals who had mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, polyclonal activation of T cells was higher in individuals who had recently experienced a mild SARS-CoV-2 infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for up to three months after mild or asymptomatic SARS-CoV-2 infections.
Simultaneous passive acoustic monitoring uncovers evidence of potentially overlooked temporal variation in an Amazonian bird community
Authors: Hopping W. Alexander , Sayers Christopher J. , Huaraca-Charca Noe Roger , Klinck Holger 
Published: September 2021

AbstractThe vocal activity and detectability of tropical birds are subject to high levels of temporal heterogeneity, but quantifying patterns of diel and day-to-day variation in complex systems is challenging with traditional point count methods. As a result, research concerning stochastic temporal effects on tropical avian assemblages is limited, typically offering only broad conclusions, e.g., overall activity is highest in the first few hours of the morning and some species are active at different times of the day. Passive acoustic monitoring introduces several advantages for studying temporal variation, particularly by enabling simultaneous and continuous data collection across adjacent sites. Here, we employed autonomous recording units to quantify temporal variation in avian vocal activity and observed species richness at an Amazonian reserve in Madre de Dios, Peru—a region featuring some of Earth’s richest, most complex avian assemblages. We manually annotated 18 dawn hour recordings, collected simultaneously from three separate days at the same six sites, which represent various microhabitats and avian community compositions. We documented significant and consistent temporal variation in avian vocal activity levels and observed species richness within the dawn hour and across days. We found that temporal effects were stronger for vocal activity than for observed species richness and that vocal activity patterns over the course of the dawn hour varied on a species-to-species basis. Our results indicate that overlooked temporal variation in Amazonian soundscapes may obfuscate the results of surveys that fail to sufficiently account for temporal variables with simultaneous monitoring. While manual analysis of large volumes of soundscape data remains challenging, such data should be collected as a supplement to traditional surveys whenever possible. Rapidly advancing research concerning the automated processing of acoustic data could lead to more efficient methods for reducing temporal bias and improving the calibration and accuracy of ornithological surveys in the tropics.
SARS-CoV-2 vaccines breakthrough infection hospitalizations after one dose in Libya: cohort study
Authors: Abdelhamid Mohamed Hadi Mohamed , Almsellati Iman A. , Annajar Badereddin B , Abdelhamid Alaa .H , Alemam Hafsa .A , Etikar Mohammed 
Published: September 2021

AbstractSARS-CoV-2 infection is widely spread over people, from youth to the elderly. Vaccination against SARS-CoV-2 is an important preventive measurement to help end the SARS-CoV-2 pandemic. From 30 April to 15 July, we collected the number of people infected with SARS-COV-2 and the mortality rate from daily reports issued by the National Center for Disease Control of Libya (NCDC). Approximately 445000 doses have been administered in Libya since 10 April, and 5 thousand doses are now being administered during this period on a daily basis. To estimate the rate of breakthrough vaccine infection of the SARS-COV-2 in Libya. We found that one dose of the three different types of vaccines had decreased the virus transmission across people and mortality rate until 10 weeks after the first dose. This study highlights the dramatic success of the early months of the nation’s coronavirus vaccines rollout.
Transient dendritic cell activation diversifies the T cell response to acute infection
Authors: Hiam-Galvez Kamir J. , DeBarge Rachel , Lareau Caleb A. , Cho Nam Woo , Yee Jacqueline L. , Okholm Trine Line H. , Spitzer Matthew H. 
Published: September 2021

AbstractThe precise timing of T cell priming during infection remains unclear. Here, we mapped the cellular dynamics of all immune lineages during acute infection with Listeria monocytogenes (Lm). We identified highly transient DC activation 2 days post-infection that functions as a critical time window for priming effector T cells. Regulation of this transient state was mediated by DC extrinsic IFNγ provided by lymphocytes. Furthermore, antigen-specific T cells that arrive late to the site of priming and miss peak DC activation acquire only memory T cell fates. This temporal regulation of fate is recapitulated by CD8+ DCs ex vivo, suggesting that shifts in activation state of a single antigen presenting cell population alter T cell fates. These results uncover a novel mechanism for temporal regulation of T cell differentiation during a dynamic immune response to acute infection.One-Sentence SummaryThe immune system generates a balanced protective response through rapidly shifting activation states and recruitment of new cells into an ongoing inflammatory landscape.
Gene flow biases population genetic inference of recombination rate
Authors: Samuk K. , Noor M.A.F. 
Published: September 2021

AbstractAccurate estimates of the rate of recombination are key to understanding a host of evolutionary processes as well as the evolution of recombination rate itself. Model-based population genetic methods that infer recombination rates from patterns of linkage disequilibrium (LD) in the genome have become a popular method to estimate rates of recombination. However, these LD-based methods make a variety of simplifying assumptions about the populations of interest that are often not met in natural populations. One such assumption is the absence of gene flow from other populations. Here, we use forward-time population genetic simulations of isolation-with-migration scenarios to explore how gene flow affects the accuracy of LD-based estimators of recombination rate. We find that moderate levels of gene flow can result in either the overestimation or underestimation of recombination rates by up to 20-50% depending on the timing of divergence. We also find that these biases can affect the detection of interpopulation differences in recombination rate, causing both false positive and false negatives depending on the scenario. We discuss future possibilities for mitigating these biases and recommend that investigators exercise caution and confirm that their study populations meet assumptions before deploying these methods.
Spatio-temporal, optogenetic control of gene expression in organoids
Authors: Legnini Ivano , Emmenegger Lisa , Zappulo Alessandra , Wurmus Ricardo , Martinez Anna Oliveras , Jara Cledi Cerda , Boltengagen Anastasiya , Hessler Talé , Mastrobuoni Guido , Rybak-Wolf Agnieszka , Kempa Stefan , Zinzen Robert , Woehler Andrew , Rajewsky Nikolaus 
Published: September 2021

AbstractOrganoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions and revealed new insights into SHH’s contribution to gene regulation in neurodevelopment.With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids.
Cytotoxic T-cell-based vaccine against SARS-CoV2: a hybrid immunoinformatic approach
Authors: Tîrziu Alexandru , Păunescu Virgil 
Published: September 2021

AbstractThis paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile and physiologically appropriate immunization method using either intra-nasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. SLPs comprising HLA class I and class II epitopes are used to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The result is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Peptides isolated from COVID-19 convalescent patients were screened for the best HLA population coverage and were tested for toxicity and allergenicity. 3D peptide folding followed by molecular docking studies provided positive results, suggesting a favourable antigen presentation.
Insight into Cross-Amyloid Interactions and Morphologies: Molecular Dynamics Simulations of Model Peptide Fragments of Amyloid-β (Aβ16-22) and Islet Amyloid Polypeptide (IAPP20-29)
Authors: Cramer N. , Kawecki G. , King K. M. , Bevan D. R. , Brown A.M. 
Published: September 2021

AbstractAmyloid-beta (Aβ) and islet amyloid polypeptide (IAPP) are small peptides, classified as amyloids, that have the potential to self-assemble and form cytotoxic species, such as small soluble oligomers and large insoluble fibrils. The formation of Aβ aggregates facilitates the progression of Alzheimer’s disease (AD), while IAPP aggregates induce pancreatic β-cell apoptosis, leading to exacerbation of Type 2 diabetes (T2D). Cross-amyloid interactions between Aβ and IAPP have been described both in vivo and in vitro, implying the role of Aβ or IAPP as modulators of cytotoxic self-aggregation of each peptide, and suggesting that Aβ-IAPP interactions are a potential molecular link between AD and T2D. Using molecular dynamics simulations, “hot spot” regions of the two peptides were studied to understand the formation of hexamers in a heterogenous and homogenous peptide-containing environment. Systems of only Aβ(16-22) peptides formed antiparallel, β-barrel-like structures, while systems of only IAPP(20-29) peptides formed stacked, parallel beta strands and had relatively unstable aggregation structures after 2 μs of simulation time. Systems containing both Aβ and IAPP (1:1 ratio) hexamers showed antiparallel, β-barrel-like structures, with an interdigitated arrangement of Aβ(16-22) and IAPP(20-29). These β-barrel structures have features of cytotoxic amyloid species identified in previous literature. Ultimately, this work seeks to provide atomistic insight into both the mechanism behind cross-amyloid interactions and structural morphologies of these toxic amyloid species.Statement of SignificanceMolecular knowledge, biophysical characterization, structural morphologies, and formation pathways of amyloid oligomers - specifically low-molecular weight, cross-amyloid oligomers - remain preliminary and undefined. Characterizing interactions between homogenous and heterogenous amyloid oligomers is of great interest given that certain oligomer morphologies contribute to cytotoxicity, eventually resulting in comorbid diseases such as Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM). Utilizing model systems (e.g., fragments of full-length peptides) and molecular dynamics (MD) simulations to probe the biophysical underpinnings of cross-amyloid oligomer structures is the first step in understanding the dynamics, stability, and potential modes of cytotoxicity of these species, providing important insights into targetable biomolecular structures.
KLC4 shapes axon arbors during development and mediates adult behavior
Authors: Haynes Elizabeth M. , Burnett Korri H. , He Jiaye , Jean-Pierre Marcel , Jarzyna Martin , Eliceiri Kevin W. , Huisken Jan , Halloran Mary C. 
Published: September 2021

AbstractDevelopment of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.
How to model DNA replication in stochastic models of synthetic gene circuits (and why)
Authors: Clamons Samuel E. , Murray Richard M. 
Published: September 2021

AbstractBiocircuit modeling sometimes requires explicit tracking of a self-replicating DNA species. The most obvious, straightforward way to model a replicating DNA is structurally unstable and leads to pathological model behavior. We describe a simple, stable replication mechanism with good model behavior and show how to derive it from a mechanistic model of ColE1 replication.
Different plasticity of bud outgrowth at cauline and rosette nodes in Arabidopsis thaliana
Authors: Fichtner Franziska , Barbier Francois F. , Kerr Stephanie C. , Dudley Caitlin , Cubas Pilar , Turnbull Colin , Brewer Philip B. , Beveridge Christine A. 
Published: September 2021

ABSTRACTShoot branching is a complex mechanism in which secondary shoots grow from buds that are initiated from meristems established in leaf axils. The model plant Arabidopsis thaliana has a rosette leaf growth pattern in the vegetative stage. After flowering initiation, the main stem starts to elongate with the top leaf primordia developing into cauline leaves. Meristems in arabidopsis are initiated in the axils of rosette or cauline leaves, giving rise to rosette or cauline buds, respectively. Plasticity in the process of shoot branching is regulated by resource and nutrient availability as well as by plant hormones. However, few studies have attempted to test whether cauline and rosette branching are subject to the same plasticity. Here, we addressed this question by phenotyping cauline and rosette branching in three arabidopsis ecotypes and several arabidopsis mutants with varied shoot architectures. Our results show that there is no negative correlation between cauline and rosette branch numbers in arabidopsis, demonstrating that there is no trade-off between cauline and rosette bud outgrowth. Through investigation of the altered branching pattern of flowering pathway mutants and arabidopsis ecotypes grown in various photoperiods and light regimes, we further elucidated that the number of cauline branches is closely related to flowering time. The number or rosette branches has an enormous plasticity compared with cauline branches and is influenced by genetic background, flowering time, light intensity and temperature. Our data reveal different plasticity in the regulation of branching at rosette and cauline nodes and promote a framework for future branching analyses.One sentence summaryDifferent plasticity of branching at cauline and rosette nodes of arabidopsis is revealed through detailed correlative analyses of branching under varied genetic and environmental contexts.
Elucidation of the molecular interactions that enable stable interaction between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study
Authors: Mohan Monisha , Anindya Roy 
Published: September 2021

ABSTRACTThe human DNA repair enzyme AlkB homologue-2 and 3 (ALKBH2 and ALKKBH3) repairs methyl adducts from genomic DNA. Overexpression of ALKBH2 and ALKBH3 has been implicated in both tumorigenesis and chemotherapy resistance in some cancers, including glioblastoma and renal cancer rendering it a potential therapeutic target and a diagnostic marker. However, no inhibitor is available against these important DNA repair proteins. Intending to repurpose a drug as an inhibitor of ALKBH2/ALKBH3, we performedin silicoevaluation of HIV protease inhibitors and identified Ritonavir as an ALKBH2-interacting molecule. Using molecular dynamics simulation, we elucidated the molecular details of Ritonavir-ALKBH2 interaction. The present work highlights that Ritonavir might be used to target the ALKBH2-mediated DNA alkylation repair.
The scratch-digging lifestyle of the Permian “microsaur”Batropetesas a model for the exaptative origin of jumping locomotion in frogs
Authors: Jansen Maren , Marjanović David 
Published: September 2021

AbstractRecent studies have shown that the Triassic stem-frogTriadobatrachuslacked the ability to jump off, but nonetheless had the forelimb strength to withstand the impact of landing from a jump. We propose a hypothesis to resolve this pseudoparadox: the strengthened forelimbs are former adaptations to forelimb-based digging that later made jumping possible by exaptation.Micro-CT data from a skeleton ofBatropetes palatinusreveal thin cortical bone, confirmingBatropetesas terrestrial. Combining adaptations to walking and digging, confirmed by statistical analyses,Batropetesis thought to have searched for food in leaf litter or topsoil. We interpretBatropetesas having used one forelimb at a time to shove leaf litter aside.Batropetesmay thus represent an analog or possibly a homolog of the digging stage that preceded the origin of Salientia.We discuss the possibility of homology with the digging lifestyles of other “microsaurs” and other amphibians.
Bioorthogonally Cross-Linked Hyaluronan-Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication
Authors: Jury Michael , Matthiesen Isabelle , Boroojeni Fatemeh Rasti , Ludwig Saskia L. , Civitelli Livia , Winkler Thomas E. , Selegård Robert , Herland Anna , Aili Daniel 
Published: September 2021

AbstractLaminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons towards development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here we show a modular hydrogel system for neural 3D cell culture, based on hyaluronan (HA) and poly(ethylene glycol) (PEG), that is cross-linked and functionalized with human recombinant LN 521 using bioorthogonal copper-free click chemistry. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of syringe extruded lt-NES, which can facilitate the development of advanced neuronal tissue and disease models and translation of stem cell-based therapies.The authors present an extracellular matrix mimicking hydrogel for 3D culture of neural cell models. Based on hyaluronic acid and poly(ethylene glycol), the hydrogel immobilizes recombinant laminin 521, associated with neuronal development. The study demonstrates support of neuroblastoma cell viability, spontaneous human neuroepithelial stem cell differentiation, and the protective effect of the hydrogels during bioprinting and syringe needle ejection.