bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of individualized brain anatomies and EEG electrode positions for auditory cortex localization
Authors: Ignatiadis Karolina , Barumerli Roberto , Tóth Brigitta , Baumgartner Robert 
Published: June 2022

ABSTRACTDue to its high temporal resolution and non-invasive nature, electroencephalography (EEG) is considered a method of great value for the field of auditory cognitive neuroscience. In performing source space analyses, localization accuracy poses a bottleneck, which precise forward models based on individualized attributes such as subject anatomy or electrode locations aim to overcome. Yet acquiring anatomical images or localizing EEG electrodes requires significant additional funds and processing time, making it an oftentimes inaccessible asset. Neuroscientific software offers template solutions, on which analyses can be based. For localizing the source of auditory evoked responses, we here compared the results of employing such template anatomies and electrode positions versus the subject-specific ones, as well as combinations of the two. All considered cases represented approaches commonly used in electrophysiological studies. We considered differences between two commonly used inverse solutions (dSPM, sLORETA) and targeted the primary auditory cortex; a notoriously small cortical region that is located within the lateral sulcus, thus more prone to errors in localization. Through systematical comparison of the outcomes in terms of auditory activity attributes and leakage quantification, we assessed how the individualization steps impacted the analyses outcomes. Both electrode locations as well as subject anatomies were found to have an effect, which though varied based on the configuration considered. When comparing the inverse solutions, we moreover found that dSPM more consistently benefited from individualization of subject characteristics. Based on the scientific question considered, our results may be used to facilitate the planning of auditory neuroscientific experiments in terms of expected infrastructure, personnel and funds.
Isolation of a novel heterodimeric PSII complex via strep-tagged PsbO
Authors: Lambertz Jan , Meier-Credo Jakob , Kucher Svetlana , Bordignon Enrica , Langer Julian D. , Nowaczyk Marc M. 
Published: June 2022

AbstractThe multi-subunit membrane protein complex Photosystem II (PSII) catalyzes the light-driven oxidation of water and with this the initial step of photosynthetic electron transport in plants, algae, and cyanobacteria. Its biogenesis is coordinated by a network of auxiliary proteins that facilitate the stepwise assembly of individual subunits and cofactors, forming various intermediate complexes until fully functional mature PSII is present at the end of the process. In the current study, we purified PSII complexes from a mutant line of the thermophilic cyanobacterium Thermosynechococcus vestitus BP-1 in which the extrinsic subunit PsbO, characteristic for active PSII, was fused with an N-terminal Twin-Strep-tag. Three distinct PSII complexes were separated by ion-exchange chromatography after the initial affinity purification. Two complexes differ in their oligomeric state (monomeric and dimeric) but share the typical subunit composition of mature PSII. They are characterized by the very high oxygen-evolving activity of approx. 6,000 µmol O2· (mg Chl·h)-1. Analysis of the third (heterodimeric) PSII complex revealed lower oxygen-evolving activity of approx. 3,000 µmol O2· (mg Chl·h)-1 and manganese content of 2.7 (± 0.2) per reaction center compared to 3.7 (± 0.2) of fully active PSII. Mass spectrometry and time-resolved fluorescence spectroscopy further indicated that PsbO is partially replaced by Psb27 in this PSII fraction, thus implying a role in the repair of the complex.
Analyzing single-cell bisulfite sequencing data withMethSCAn
Authors: Kremer Lukas P. M. , Braun Martina M. , Ovchinnikova Svetlana , Küchenhoff Leonie , Cerrizuela Santiago , Martin-Villalba Ana , Anders Simon 
Published: June 2022

AbstractSingle-cell bisulfite sequencing (scBS) is a technique that enables the assessment of DNA methylation at single-base pair and single-cell resolution. The analysis of large datasets obtained from scBS requires preprocessing to reduce data size, improve signal-to-noise ratio, and provide interpretability. Typically, this is achieved by dividing the genome into large tiles and averaging the methylation signals within each tile.Here, we demonstrate that this coarse-graining approach can lead to signal dilution. As an alternative, we propose improved strategies to identify more informative regions for methylation quantification, and a more accurate quantitation method than simple averaging. Our approach enables better discrimination of cell types and other features of interest and reduces the need for large numbers of cells. We also present an approach to detect differentially methylated regions (DMRs) between groups of cells, and demonstrate its ability to identify biologically meaningful regions that are associated with genes involved in the core functions of specific cell types.To facilitate the analysis of scBS data, we have developed a software tool calledMeth-SCAnthat implements these methods and provides additional functionality.
Sensory input to cortex encoded on low-dimensional periphery-correlated subspaces
Authors: Barreiro Andrea K , Fontenele Antonio J , Ly Cheng , Raju Prashant , Gautam Shree Hari , Shew Woodrow L 
Published: June 2022

AbstractAs information about the world is conveyed from the sensory periphery to central neural circuits, it mixes with complex ongoing cortical activity. How do neural populations keep track of sensory signals, separating them from noisy ongoing activity? Here we show that sensory signals are encoded more reliably in certain low-dimensional subspaces. These coding subspaces are defined by correlations between neural activity in primary sensory cortex and upstream sensory brain regions; the most correlated dimensions were best for decoding. We analytically show that these correlation-based coding subspaces improve, reaching optimal limits (without an ideal observer) as noise correlations between cortex and upstream regions are reduced. We show that this principle generalizes across diverse sensory stimuli in the olfactory system and the visual system of awake mice. Our results demonstrate an algorithm the cortex may use to multiplex different functions, processing sensory input in low dimensional subspaces separate from other ongoing functions.Significance statementTraditionally, primary sensory cortex was thought to have one job – processing sensory signals. As technical advances allow more holistic measurements of the brain and body in action, it has become clear that primary sensory cortex is involved with many other aspects of brain function, not just dealing with sensory input. How can a single neural circuit juggle multiple jobs simultaneously? Here we use numerical, analytical, and experimental methods to demonstrate an algorithm the brain may use to solve this problem by separating different jobs into different subspaces defined by correlations between primary sensory cortex and the brain regions that source the sensory input signals.
Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency
Authors: Leithner Alexander , Staufer Oskar , Mitra Tanmay , Liberta Falk , Valvo Salvatore , Kutuzov Mikhail , Dada Hannah , Spaeth Jacob , Zhou Sally , Schiele Felix , Reindl Sophia , Nar Herbert , Hoerer Stefan , Crames Maureen , Comeau Stephen , Young David , Low Sarah , Jenkins Edward , Davis Simon J. , Klenerman David , Nixon Andrew , Pefaur Noah , Wyatt David , Dushek Omer , Kasturirangan Srinath , Dustin Michael L. 
Published: June 2022

AbstractBispecific T-cell engagers (TcEs) link T cell receptors to tumor-associated antigens on cancer cells, forming cytotoxic immunological synapses (IS). Close membrane-to-membrane contact (≤13 nm) has been proposed as a key mechanism of TcE function. To investigate this and identify potential additional mechanisms, we compared four immunoglobulin G1-based (IgG1) TcE Formats (A-D) targeting CD3ε and Her2, designed to create varying intermembrane distances (A<B<C<D). Small-angle X-ray scattering (SAXS) and modelling of the conformational states of isolated TcEs and TcE-antigen complexes predicted close-contacts (≤13 nm) for Formats A and B and far-contacts (≥18 nm) for Formats C and D. In supported lipid bilayer (SLB) model interfaces, Formats A and B recruited, whereas Formats C and D repelled, CD2-CD58 interactions. Formats A and B also excluded bulky Quantum dots more effectively. SAXS also revealed that TcE-antigen complexes formed by Formats A and C were less flexible than complexes formed by Formats B and D. Functional data with Her2-expressing tumor cells showed cytotoxicity, surface marker expression and cytokine release following the order A>B=C>D. In a minimal system for IS formation on SLBs, TcE performance followed the trend A=B=C>D. Addition of close-contact requiring CD58 co-stimulation revealed phospholipase C-γ activation matching cytotoxicity with A>B=C>D. Our findings suggest that, when adhesion is equivalent, TcE potency is determined by two parameters: contact distance and flexibility. Both the close/far-contact formation axis and the low/high flexibility axis significantly impact TcE potency, explaining the similar potency of Format B (close-contact/high flexibility) and C (far-contact/low flexibility).Significance statementBispecific T-cell engagers (TcEs) are immunotherapeutic drugs that trigger the destruction of cancer cells by linking T cells to cancer cell through specific surface molecules (antigens). We designed a series of TcEs with varying distances between their binding sites and flexibilities of the TcE-antigen complexes. By combining structural and functional analyses, we confirmed close-contact formation between T cells and cancer cells as a critical determinant, mediated by co-activating receptors. Furthermore, we also identified molecular flexibility of the TcE-antigen complex as a further critical parameter for TcE potency. These findings provide novel insights into TcE function and highlight the importance of both parameters for future research and the design of improved immunotherapies.
qHTSWaterfall: 3-dimensional visualization software for quantitative high-throughput screening (qHTS) data
Authors: Queme Bryan , Braisted John C. , Dranchak Patricia , Inglese James 
Published: June 2022

AbstractHigh throughput screening (HTS) is widely used in drug discovery and chemical biology to identify and characterize agents having pharmacologic properties often by evaluation of large chemical libraries. Standard HTS data can be simply plotted as an x-y graph usually represented as % activity of a compound tested at a single concentration vs compound ID, whereas quantitative HTS (qHTS) data incorporates a third axis represented by concentration. By virtue of the additional data points arising from the compound titration and the incorporation of logistic fit parameters that define the concentration-response curve, such as EC50 and Hill slope, qHTS data has been challenging to display on a single graph. Here we provide a flexible solution to the rapid plotting of complete qHTS data sets to produce a 3-axis plot we call qHTS Waterfall Plots. The software described here can be generally applied to any 3-axis dataset and is available as both an R package and an R shiny application.
Brain-Controlled Electrical Stimulation Restores Continuous Finger Function
Authors: Nason-Tomaszewski Samuel R. , Mender Matthew J. , Kennedy Eric , Lambrecht Joris M. , Kilgore Kevin L. , Chiravuri Srinivas , Kumar Nishant Ganesh , Kung Theodore A. , Willsey Matthew S. , Chestek Cynthia A. , Patil Parag G. 
Published: June 2022

ABSTRACTBrain-machine interfaces have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user’s own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. In a one-dimensional, continuous, finger-related target acquisition task, the monkey improved his success rate to 83% (1.5s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5s median acquisition, equivalent to chance) when attempting to use his temporarily paralyzed hand. With two monkeys under general anesthesia, we found FES alone could control the monkeys’ fingers to rapidly reach targets in a median 1.1s but caused oscillation about the target. Finally, when attempting to perform a virtual two-finger continuous target acquisition task in brain-control mode following temporary hand paralysis, we found performance could be completely recovered by executing recalibrated feedback-intention training one time following temporary paralysis. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting performance factor in a BCFES neuroprosthesis.
Evaluation of OCT biomarker changes in treatment-naive neovascular AMD using a deep semantic segmentation algorithm
Authors: Asani Ben , Holmberg Olle , Schiefelbein Johannes B , Hafner Michael , Herold Tina , Spitzer Hannah , Siedlecki Jakob , Kern Christoph , Kortuem Karsten U. , Frishberg Amit , Theis Fabian J. , Priglinger Siegfried G 
Published: June 2022

AbstractPurposeTo determine real life quantitative changes in OCT biomarkers in a large set of treatment naive patients undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing, to the best of our knowledge, the first benchmark results for automatic segmentation of 11 OCT features including biomarkers that are in line with the latest consensus nomenclature of the AAO for age-related macular degeneration (AMD).DesignRetrospective study.ParticipantsSegmentation algorithm training set of 458 volume scans as well as single scans from 363 treatment naive patients for the analysis.MethodsTraining of a Deep U-net based semantic segmentation ensemble algorithm leveraging multiple deep convolutional neural networks for state of the art semantic segmentation performance as well as analyzing OCT features prior to, after 3 and 12 months of anti-VEGF therapy.Main outcome measuresF1 score for the segmentation efficiency and the quantified volumes of 11 OCT features.ResultsThe segmentation algorithm achieved high F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03µm3to 0.01µm3, p<0.001), subretinal fluid (0.08µm3to 0.01µm3, p<0.001), subretinal hyperreflective material (0.02µm3to 0.01µm3, p<0.001), fibrovascular PED (0.12µm3to 0.09µm3, p=0.02) and central retinal thickness C0 (225.78µm3to 169.40µm3).The amounts of intraretinal fluid, fibrovascular PED and ERM were predictive of poor outcome.ConclusionsThe segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF therapy provokes most potent changes in the first 3 months and afterwards only acts as a stabilizing agent. Furthermore, a gradual loss of RPE hints at a progressing decline of visual acuity even beyond month 12. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen.PrécisNovel high performance segmentation algorithm shows most volumetric changes under anti-VEGF therapy in oct biomarkers occur in the first 3 months. Afterwards the injections seem only to serve as a stabilizing agent.
Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors
Authors: Buss Lewis F , Prete Carlos A , Whittaker Charles , Salomon Tassila , Oikawa Marcio K. , Pereira Rafael H. M. , Moura Isabel C. G. , Delerino Lucas , Franca Rafael F. O. , Miyajima Fabio , Mendrone-Junior Alfredo , de Almeida Neto César , Salles Nanci A. , Ferreira Suzete C. , Fladzinski Karine A. , de Souza Luana M. , Schier Luciane K. , Inoue Patricia M. , Xabregas Lilyane A. , Crispim Myuki A. E. , Fraiji Nelson , Carlos Luciana M. B. , Pessoa Veridiana , Ribeiro Maisa A. , de Souza Rosenvaldo E. , Cavalcante Anna F. , Valença Maria I. B. , da Silva Maria V. , Lopes Esther , Filho Luiz A. , Mateos Sheila O. G. , Nunes Gabrielle T. , Schlesinger David , da Silva Sônia Mara Nunes , Silva-Junior Alexander L. , Castro Marcia C , Nascimento Vítor H. , Dye Christopher , Busch Michael P , Faria Nuno R , Sabino Ester C 
Published: June 2022

AbstractBackgroundSARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants which nears 100% in many settings. New analytic approaches are required to exploit the full information in serosurvey data.MethodUsing a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titres in serial cross-sectional monthly samples of routine blood donations across seven Brazilian state capitals (March 2021-November 2021). In an ecological analysis (unit of analysis: age-city-calendar month) we assessed the relative contributions of prior attack rate and vaccination to antibody titre in blood donors. We compared blood donor anti-S titre across the seven cities during the growth phase of the Delta variant of concern (VOC) and use this to predict the resulting age-standardized incidence of severe COVID-19 cases.ResultsOn average we tested 780 samples per month in each location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven proximally by vaccination, mean antibody titre increased 16-fold over the study. The extent of prior natural infection shaped this process, with the greatest increases in antibody titres occurring in cities with the highest prior attack rates. Mean anti-S IgG was a strong predictor (adjusted R2 =0.89) of the number of severe cases caused by the Delta VOC in the seven cities.ConclusionsSemi-quantitative anti-S antibody titres are informative about prior exposure and vaccination coverage and can inform on the potential impact of future SARS-CoV-2 variants.SummaryIn the face of near 100% SARS-CoV-2 seroprevalence, we show that average semi-quantitative anti-S titre predicted the extent of the Delta variant’s spread in Brazil. This is a valuable metric for future seroprevalence studies.
White matter microstructure in face and body networks predicts facial expression and body posture perception across development
Authors: Ward Isobel L. , Raven Erika P. , de la Rosa Stephan , Jones Derek K. , Teufel Christoph , von dem Hagen Elisabeth 
Published: June 2022

AbstractFacial expression and body posture recognition have protracted developmental trajectories. Interactions between face and body perception, such as the influence of body posture on facial expression perception, also change with development. While the brain regions underpinning face and body processing are well-defined, little is known about how white-matter tracts linking these regions relate to perceptual development. Here, we obtained complementary diffusion magnetic resonance imaging (MRI) measures (fractional anisotropy FA, spherical mean), and a quantitative MRI myelin-proxy measure (R1), within white-matter tracts of face- and body-selective networks in children and adolescents and related these to perceptual development. In tracts linking occipital and fusiform face areas, facial expression perception was predicted by age-related microstructural development, as measured byand R1, as well as age-independent individual differences in microstructure, as measured by FA. Tract microstructure linking the body region in posterior superior temporal sulcus with anterior temporal lobe (ATL) was related to the influence of body on facial expression perception, supporting ATL as a site of face and body network convergence. Overall, our results highlight age-dependent and age-independent constraints that white-matter microstructure poses on perceptual abilities during development and the importance of complementary microstructural measures in linking brain structure and behaviour.
Axo-vascular coupling mediated by oligodendrocytes
Authors: Restrepo Alejandro , Trevisiol Andrea , Restrepo-Arango Camilo , Depp Constanze , Sasmita Andrew Octavian , Keller Annika , Tzvetanova Iva D. , Hirrlinger Johannes , Nave Klaus-Armin 
Published: June 2022

AbstractThe high energy requirements of the cortical gray matter are met by the precise cooperation of neurons, glia, and vascular cells in a process known as neurovascular coupling (NVC). In contrast, the existence and significance of NVC in white matter (WM) are still debated and basic regulatory mechanisms are unknown. We recently discovered that oligodendrocytes sense the spiking axons’ activity via NMDA receptors and regulate their cell surface expression of glucose transporter GLUT1 allowing an increase in glycolytic metabolism that enables lactate release to metabolically support the axons. Here, we show for the mouse optic nerve (ON), a model WM tract, that the vascular support is also dynamically controlled. Axonal spiking activity induces small vessel dilations which are sustained for more than 20 minutes upon the ending of electrical stimulation. Pharmacological inhibition shows that the electrically evoked dilation is mediated by the prostaglandin E2 receptor EP4 and can be modulated by the oxygen concentration, as has been shown in the grey matter. Importantly, we found in ONs from conditional mouse mutants that oligodendroglial NMDA receptors are required for this type of neurovascular response, demonstrating a critical role of oligodendrocytes in coupling axonal activity to pericyte function. Reminiscent of NVC in cortical slices, the “axo-vascular” response is slower and may represent a more rudimentary form of neurovascular coupling.
Sequence-independent substrate selection by the eukaryotic wobble base deaminase ADAT2/3 involves multiple protein domains and distortion of the tRNA anticodon loop
Authors: Dolce Luciano G. , Zimmer Aubree A. , Tengo Laura , Weis Félix , Rubio Mary Anne T. , Alfonzo Juan D. , Kowalinski Eva 
Published: June 2022

AbstractThe essential deamination of adenosine A34 to inosine at the wobble base is the individual tRNA modification with the greatest effects on mRNA decoding, empowering a single tRNA to translate three different codons. To date, many aspects of how eukaryotic deaminases specifically select their multiple substrates remain unclear. Here, using cryo-EM, we present the first structure of a eukaryotic ADAT2/3 deaminase bound to a full-length tRNA, revealing that the enzyme distorts the anticodon loop, but in contrast to the bacterial enzymes, selects its substrate via sequence-independent contacts of eukaryote-acquired flexible or intrinsically unfolded motifs distal from the conserved catalytic core. A novel gating mechanism for substrate entry to the active site is identified. Our multi-step tRNA recognition model yields insights into how RNA editing by A34 deamination evolved, shaped the genetic code, and directly impacts the eukaryotic proteome.