bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infection-induced immunity and the duration of viral shedding: results from a Nicaraguan household cohort study
Authors: Maier Hannah E. , Plazaola Miguel , Lopez Roger , Sanchez Nery , Saborio Saira , Ojeda Sergio , Barilla Carlos , Kuan Guillermina , Balmaseda Angel , Gordon Aubree 
Published: June 2022

BackgroundMuch of the world’s population has been infected with SARS-CoV-2. Thus, infection-induced immunity will play a critical role in future SARS-CoV-2 transmission. We investigated the impact of immunity from prior infection on viral shedding duration and viral load.MethodsWe conducted a household cohort study in Managua, Nicaragua with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity, respectively. Blood samples were collected in Feb/March and Oct/Nov 2020 and 2021, and surrounding household intensive monitoring periods. We used accelerated failure time models to compare shedding times. Participants vaccinated ≥14 days prior to infection were excluded from primary analyses.ResultsThere were 600 RT-PCR-confirmed SARS-CoV-2 infections between May 1, 2020 and March 10, 2022 with ELISA data prior to infection. Prior infection was associated with 48% shorter shedding times, event time ratio (ETR) 0.52 (95% CI: 0.39-0.69, mean shedding: 13.7 vs 26.4 days). A 4-fold higher anti-SARS-CoV-2 spike titer was associated with 17% shorter shedding (ETR 0.83, 95% CI: 0.78-0.90). Similarly, maximum viral loads (lowest CT) were lower for previously infected individuals (mean CT 29.8 vs 28.0, p = 4.02×10−3). Shedding was shorter in previously infected adults and children ≥10 years, but not in children 0-9 years; there was little difference in CT levels for previously infected vs naïve adults above age 60.ConclusionsPrior infection-induced immunity was associated with shorter viral shedding and lower viral loads.
Seasonal plasticity in morphology and metabolism differs between migratory North American and resident Costa Rican monarch butterflies
Authors: Tenger-Trolander Ayşe , Julick Cole R. , Lu Wei , Green Delbert André , Montooth Kristi L. , Kronforst Marcus R. 
Published: June 2022

AbstractEnvironmental heterogeneity in temperate latitudes is expected to maintain seasonally plastic life-history strategies that include the tuning of morphologies and metabolism that support overwintering. For species that have expanded their ranges into tropical latitudes, it is unclear the extent to which the capacity for plasticity will be maintained or will erode with disuse. The migratory generations of the North American (NA) monarch butterflyDanaus plexippuslead distinctly different lives from their summer generation NA parents and their tropical descendants living in Costa Rica (CR). NA migratory monarchs postpone reproduction, travel thousands of kilometers south to overwinter in Mexico, and subsist on little food for months. Whether recently dispersed populations of monarchs such as those in Costa Rica, which are no longer subject to selection imposed by migration, retain ancestral seasonal plasticity is unclear. To investigate differences in seasonal plasticity, we reared NA and CR monarchs in summer and autumn in Illinois, USA, and measured seasonal reaction norms for aspects of morphology and metabolism related to flight. NA monarchs were seasonally plastic in forewing and thorax size, increasing wing area and thorax to body mass ratio in autumn. While CR monarchs increased thorax mass in autumn, they did not increase the area of the forewing. NA monarchs maintained similar resting and maximal flight metabolic rates across seasons. However, CR monarchs had elevated metabolic rates in autumn. Our findings suggest that the recent expansion of monarchs into habitats that support year-round breeding may be accompanied by (1) the loss of some aspects of morphological plasticity as well as (2) the underlying physiological mechanisms that maintain metabolic homeostasis in the face of temperature heterogeneity.
Functional and pharmacological analyses of visual habituation learning in larval zebrafish
Authors: Lamiré Laurie-Anne , Haesemeyer Martin , Engert Florian , Granato Michael , Randlett Owen 
Published: June 2022

AbstractHabituation allows animals to learn to ignore persistent but inconsequential stimuli. Despite being the most basic form of learning, a consensus model on the underlying mechanisms has yet to emerge. To probe relevant mechanisms we took advantage of a visual habituation paradigm in larval zebrafish, where larvae reduce their reactions to abrupt global dimming (a dark flash). We used Ca2+imaging during repeated dark flashes and identified 12 functional classes of neurons that differ based on their rate of adaptation, stimulus response shape, and anatomical location. While most classes of neurons depressed their responses to repeated stimuli, we identified populations that did not adapt, or that potentiated their response. These neurons were distributed across brain areas, consistent with a distributed learning process. Using a small molecule-screening approach, we confirmed that habituation manifests from multiple distinct molecular mechanisms, and we have implicated molecular pathways in habituation, including: Melatonin, Estrogen and GABA signaling. However, by combining anatomical analyses and pharmacological manipulations with Ca2+imaging, we failed to identify a simple relationship between pharmacology, altered activity patterns, and habituation behaviour. Collectively, our work indicates that habituation occurs via a complex and distributed plasticity processes that cannot be captured by a simple model. Therefore, untangling the mechanisms of habituation will likely require dedicated approaches aimed at sub-component mechanisms underlying this multidimensional learning process.
Coopting T cell proximal signaling molecules enables Boolean logic-gated CAR T cell control
Authors: Tousley Aidan M. , Rotiroti Maria Caterina , Labanieh Louai , Rysavy Lea Wenting , Rietberg Skyler P. , de la Serna Eva L. , Dalton Guillermo Nicolas , Klysz Dorota , Weber Evan W. , Kim Won-Ju , Xu Peng , Sotillo Elena , Dunn Alexander R. , Mackall Crystal L. , Majzner Robbie G. 
Published: June 2022

Introductory paragraphWhile CAR T cells have altered the treatment landscape for B cell malignancies, the risk of on-target, off-tumor toxicity has hampered their development for solid tumors because most target antigens are shared with normal cells1,2. Researchers have attempted to apply Boolean logic gating to CAR T cells to prevent on-target, off-tumor toxicity3–7; however, a truly safe and effective logic-gated CAR has remained elusive8. Here, we describe a novel approach to CAR engineering in which we replace traditional ITAM-containing CD3ζ domains with intracellular proximal T cell signaling molecules. We demonstrate that certain proximal signaling CARs, such as a ZAP-70 CAR, can activate T cells and eradicate tumorsin vivowhile bypassing upstream signaling proteins such as CD3ζ. The primary role of ZAP-70 is to phosphorylate LAT and SLP-76, which form a scaffold for the propagation of T cell signaling. We leveraged the cooperative role of LAT and SLP-76 to engineerLogic-gatedIntracellularNetworK(LINK) CAR, a rapid and reversible Boolean-logic AND-gated CAR T cell platform that outperforms other systems in both efficacy and the prevention of on-target, off-tumor toxicity. LINK CAR will dramatically expand the number and types of molecules that can be targeted with CAR T cells, enabling the deployment of these powerful therapeutics for solid tumors and diverse diseases such as autoimmunity9and fibrosis10. In addition, this work demonstrates that the internal signaling machinery of cells can be repurposed into surface receptors, a finding that could have broad implications for new avenues of cellular engineering.
Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models
Authors: de Wildt Bregje W.M , van der Meijden Robin , Bartels Paul A.A. , Sommerdijk Nico A.J.M. , Akiva Anat , Ito Keita , Hofmann Sandra 
Published: June 2022

AbstractHuman in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell-matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone-mimetic template was developed in this study, inspired by bone’s extracellular matrix composition and organization. Silk fibroin (SF) was used as an organic matrix, poly-aspartic acid (pAsp) was used to mimic the functionality of non-collagenous proteins, and 10x simulated body fluid served as mineralization solution. By using pAsp in the mineralization solution, minerals were guided towards the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments were performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts was tracked with non-destructive micro-computed tomography and medium analyses over a period of 42 days. The mineralized scaffolds supported osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell-matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell-matrix interactions need to be targeted.
COVFlow: phylodynamics analyses of viruses from selected SARS-CoV-2 genome sequences
Authors: Danesh Gonché , Boennec Corentin , Verdurme Laura , Roussel Mathilde , Trombert-Paolantoni Sabine , Visseaux Benoit , Haim-Boukobza Stéphanie , Alizon Samuel 
Published: June 2022

AbstractPhylodynamic analyses can generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce theCOVFlowpipeline, accessible athttps://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in theBeast2software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
3D single-cell shape analysis using geometric deep learning
Authors: De Vries Matt , Dent Lucas , Curry Nathan , Rowe-Brown Leo , Bousgouni Vicky , Tyson Adam , Dunsby Christopher , Bakal Chris 
Published: June 2022

AbstractAberrations in 3D cell morphogenesis are linked to diseases such as cancer. Yet there is little systems-level understanding of cell shape determination in 3D, largely because there is a paucity of data-driven methods to quantify and describe 3D cell shapes. We have addressed this need using unsupervised geometric deep learning to learn shape representations of over 95,000 melanoma cells imaged by 3D high-throughput light-sheet microscopy. We used a dynamic graph convolutional foldingnet autoencoder with improved deep embedded clustering to simultaneously learn lower-dimensional representations and classes of 3D cell shapes. We describe a landscape of 3D cell morphology using deep learning-derived 3D quantitative morphological signatures (3DQMS) across different substrate geometries, following treatment by different clinically relevant small molecules and systematic gene depletion in high-throughput. By data integration, we predict modes of action for different small molecules providing mechanistic insights and blueprints for biological re-engineering. Finally, we provide explainability and interpretability for deep learning models.
Alternative host shapes transmission and life-history trait correlations in a multi-host plant pathogen
Authors: Susi Hanna 
Published: June 2022

AbstractMost pathogens are generalists capable of infecting multiple host species or strains. Trade-offs in performance among different hosts are expected to limit the evolution of generalism. Despite the commonness of generalism, the variation in infectivity, transmission, and trade-offs in performance among host species have rarely been studied in the wild. To understand the ecological and evolutionary drivers of multi-host pathogen infectivity and transmission potential, I studied disease severity, transmission dynamics and infectivity variation of downy mildew pathogenPeronospora sparsaon its three host plantsRubus arcticus, R. chamaemorus, andR. saxatilis. In a survey of 19 wild and cultivated sites of the three host species, disease severity varied by host species and by whether the focal host species grew in shared habitat with other host species. Generally, the presence of an alternative host resulted in lower disease severity. To understand how alternative host presence and plant diversity affect on transmission of the pathogen, I conducted a trap plant experiment. In contrast to the field survey observations, the presence ofR. saxatiliswas positively correlated with transmission to trap plants. To understand how resistance toP. sparsavaries among host species and genotypes, I conducted an inoculation experiment using 10P. sparsastrains from different locations and 20 genotypes of the three host species. Significant variation in infectivity was found among host genotypes but not among host species. The pathogens strains originating form sites withR. saxatiliswere less infective than those without. When trade-offs for infectivity were tested, high infectivity in one host species correlated with high infectivity in another host species. However, when pathogen transmission-related life-history correlations were tested, a positive correlation was found inR. arcticusbut not inR. saxatilis. The results suggest that host resistance may shape pathogen life-history evolution with epidemiological consequences in a multi-host pathogen.
Influence of short and long term processes on SAR11 communities in open ocean and coastal systems
Authors: Bolaños Luis M. , Tait Karen , Somerfield Paul J. , Parsons Rachel J. , Giovannoni Stephen J. , Smyth Timothy , Temperton Ben 
Published: June 2022

AbstractSAR11 bacteria dominate the surface ocean and are major players in converting fixed carbon back to atmospheric carbon dioxide. The SAR11 clade is comprised of niche-specialized ecotypes that display distinctive spatiotemporal transitions. We analysed SAR11 ecotype seasonality in two long-term 16S rRNA amplicon time series representing different North Atlantic regimes: the Sargasso Sea (subtropical ocean-gyre; BATS) and the temperate coastal Western English Channel (WEC). Using phylogenetically resolved amplicon sequence variants (ASVs), we evaluated seasonal environmental constraints on SAR11 ecotype periodicity. Despite large differences in temperature and nutrient availability between the two sites, at both SAR11 succession was defined by summer and winter clusters of ASVs. Summer cluster was dominated by ecotype Ia.3 in both sites. Winter clusters were dominated by ecotypes Ib and IIa.A at BATS and Ia.1 and IIa.B at WEC. A two-year weekly analysis within the WEC time series showed that the response of SAR11 communities to short-term environmental fluctuations was variable. In 2016, community shifts were abrupt and synchronised to environmental shifts. However, in 2015, changes were gradual and decoupled from environmental fluctuations, likely due to increased mixing from strong winds. We demonstrate that interannual weather variability disturb the pace of SAR11 seasonal progression.
Water Network in the Binding Pocket of Fluorinated BPTI-Trypsin Complexes - Insights from Simulation and Experiment
Authors: Wehrhan Leon , Leppkes Jakob , Dimos Nicole , Loll Bernhard , Koksch Beate , Keller Bettina G. 
Published: June 2022

AbstractStructural waters in the S1 binding pocket ofβ-trypsin are critical for the stabilization of the complex ofβ-trypsin with its inhibitor bovine pancreatic trypsin inhibitor (BPTI). The inhibitor strength of BPTI can be modulated by replacing the critical lysine residue at the P1 position by non-natural amino acids. We study BPTI variants in which the critical Lys15 in BPTI has been replaced byα-aminobutyric acid (Abu) and its fluorinated derivatives monofluoroethylglycine (MfeGly), difluoroethylglycine (DfeGly) and trifluoroethylglycine (TfeGly). We investigate the hypothesis that additional water molecules in the binding pocket can form specific non-covalent interactions to the fluorinated side chains and thereby act as an extension of the inhibitors. We report potentials of mean force (PMF) of the unbinding process for all four complexes and enzyme activity inhibition assays. Additionally, we report the protein crystal structure of the Lys15MfeGly-BPTI-β-trypsin complex (pdb: 7PH1). Both, experimental and computational data, show a step-wise increase in inhibitor strength with increasing fluorination of the Abu side chain. The PMF additionally shows a minimum for the encounter complex and an intermediate state just before the bound state. In the bound state, the computational analysis of the structure and dynamics of the water molecules in the S1 pocket shows a highly dynamic network of water molecules that does not indicate a rigidification or stabilizing trend in regards to energetic properties that could explain the increase in inhibitor strength. The analysis of the enthalpy and the entropy of the water molecules in the S1 binding pocket using Grid Inhomogeneous Solvation Theory confirms this result. Overall, fluorination systematically changes the binding affinity but the effect cannot be explained by a persistent water network in the binding pocket. Other effects, such as the hydrophobicity of fluorinated amino acids and the stability of the encounter complex as well as the additional minimum in the potential of mean force in the bound state, likely influence the affinity more directly.TOC GRAPHIC
A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings
Authors: Stam M.J. , van Wijk B.C.M. , Sharma P. , Beudel M. , Piña-Fuentes D.A. , de Bie R.M.A. , Schuurman P.R. , Neumann W.-J. , Buijink A.W.G. 
Published: June 2022

AbstractObjectiveSensing-enabled neurostimulators for deep brain stimulation (DBS) therapy record neural activity directly from the stimulating electrodes in the form of local field potentials (LFPs). However, these LFPs are often contaminated with electrocardiographic (ECG) artifacts that impede the detection of physiomarkers for adaptive DBS research. This study systematically compared the ability of different ECG suppression methods to recover disease-specific electrical brain activity from ECG-contaminated LFPs.ApproachThree ECG suppression methods were evaluated: (1) QRS interpolation of the Perceive toolbox, (2) four variants of a template subtraction method, and (3) sixteen variants of a singular value decomposition (SVD) method. The performance of these methods was examined using LFPs recorded with the Medtronic PerceptTM PC system from the subthalamic nucleus in nine patients with Parkinson’s disease while stimulation was turned off (“OFF-DBS”; anode disconnected) and while stimulation was turned on at 0 mA (“ON-DBS 0 mA”; anode connected). In addition, ECG-contaminated LFPs were simulated by scaling a co-recorded external ECG signal and adding it to the OFF-DBS LFPs.Main ResultsECG artifacts were present in 10 out of 18 ON-DBS 0 mA recordings. All ECG suppression methods were able to drastically reduce the percent difference of beta band (13 – 35 Hz) spectral power and at least partly recover the beta peak and beta burst dynamics. Using predetermined R-peaks improved the performance of the ECG suppression methods. Lengthening the time window around the R-peaks resulted in stronger reduction in artifact-induced beta band power but at an increased risk of flattening the beta peak and loss of beta burst dynamics.SignificanceThe SVD method formed the preferred trade-off between artifact cleaning and signal loss, as long as its parameter settings (time window around the R-peaks; number of components) are adequately chosen.
The IgCAM BT-IgSF (IgSF11) is essential for connexin43-mediated astrocyte-astrocyte and ependymal cell-cell coupling in mice
Authors: Pelz Laura , Dossou Laura , Kompier Nine , Juttner Rene , Siemonsmeier Gabrielle , Meyer Niklas , Lowenstein Elijah David , Lahmann Ines , Kettenmann Helmut , Birchmeier Carmen , Rathjen Fritz Gunter 
Published: June 2022

AbstractThe type I transmembrane protein BT-IgSF is predominantly localized in the brain and testes. It belongs to the CAR subgroup of Ig cell adhesion proteins, which have been hypothesized to regulate connexin expression or localization. Here, we studied the putative link between BT-IgSF and connexins in astrocytes, ependymal cells and neurons of the mouse. Global knockout of BT-IgSF caused an increase in the clustering of connexin43 (Gja1), but not of connexin30 (Gjb6), on astrocytes and ependymal cells. Additionally, knockout animals displayed reduced expression levels of connexin43 protein in the cortex and hippocampus. Importantly, analysis of biocytin spread in hippocampal or cortical slices from mature mice of either sex revealed a decrease in astrocytic cell-cell coupling in the absence of BT-IgSF. Blocking either protein biosynthesis or proteolysis showed that the lysosomal pathway increased connexin43 degradation. Localization of connexin43 in subcellular compartments was not impaired in the mutant. In contrast to connexin43 the localization and expression of connexin36 (Gjd2) on neurons was not affected by the absence of BT-IgSF. Overall, our data indicate that the IgCAM BT-IgSF is essential for correct gap junction-mediated astrocyte-to-astrocyte and ependymal cell-to-ependymal cell communication.Significance StatementAstrocytes regulate a variety of physiological processes in the developing and adult brain that are essential for proper brain function. Astrocytes form extensive networks in the brain and communicate via gap junctions. Disruptions of gap junction coupling are found in several diseases such as neurodegeneration or epilepsy. Here, we demonstrate that the cell adhesion protein BT-IgSF is essential for gap junction mediated coupling between astrocytes in the cortex and hippocampus.