bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha suppression during prehension indicates neural motor drive inhibition
Authors: Ortiz Oscar , Kuruganti Usha , Chester Victoria , Wilson Adam , Blustein Daniel 
Published: December 2022

AbstractChanges in alpha band activity (8-12 Hz) have been shown to indicate the inhibition of engagement of brain regions during cognitive tasks, reflecting real-time cognitive load. Despite this, its feasibility to be used in a more dynamic environment with ongoing motor corrections has not been studied. This research used electroencephalography (EEG) to explore how different brain regions are engaged during a simple grasp and lift task where unexpected changes to the object’s properties are introduced. To our knowledge, this is the first study to show alpha activity changes related to motor error correction occur only in motor-related areas (i.e. central areas), but not in error processing areas (ie. fronto-parietal network). This suggests that oscillations over motor areas could reflect inhibition of motor drive related to motor error correction, thus being a potential cortical electrophysiological biomarker for the process, and not solely as a proxy for cognitive demands. This observation is particularly relevant in scenarios where these signals are used to evaluate high cognitive demands co-occurring with high levels of motor errors and corrections, such as prosthesis use. The establishment of electrophysiological biomarkers of mental resource allocation during movement and cognition can help identify indicators of mental workload and motor drive, which may be useful for improving brain-machine interfaces.New and NoteworthyThis research expands on previous fMRI literature by demonstrating that alpha band suppression, an EEG metric with high temporal resolution, occurs over the primary sensorimotor area during error correction of hand movements. This furthers our understanding of alpha suppression beyond processes related to cognitive demands by highlighting how motor control also influences this frequency band. Recognizing that alpha band activity is modulated by both motor and cognitive processes is important in situations where high cognitive demands can lead to a high level of movement errors. Interpretations of such modulation are often attributed only to cognitive demands, whereas a motor process may also play a factor. Furthermore, alpha suppression could be used as a biomarker for error correction with applications in human machine interfaces, such as neuroprostheses.
Transcriptomic and DNA methylation modifications during fruit ripening and in response to ABA treatment in sweet cherry
Authors: Kuhn Nathalie , Arellano Macarena , Ponce Claudio , Hodar Christian , Correa Francisco , Multari Salvatore , Martens Stefan , Carrera Esther , Donoso José Manuel , Meisel Lee A. 
Published: December 2022

AbstractAbscisic acid (ABA) plays a key role in the ripening process of non-climacteric fruits, triggering pigment production, fruit softening, and sugar accumulation. Transcriptomic studies show that ABA modifies the expression of several ripening-related genes, but to date, the epigenetic approach has not been utilized to characterize the role of ABA during this process. Therefore, this work aimed to perform transcriptomic and DNA methylation analyses of fruit samples treated with ABA during the fruit ripening process in the non-climacteric sweet cherry model. RNA-seq analyses revealed an overrepresentation of transcripts annotated in functional categories related to ABA response, secondary metabolism, and sugar synthesis. In contrast, Whole Genome Bisulfite Sequencing (WGBS) revealed DNA hypomethylation in the 5’UTR region of genes related to carotene catabolism. Genes encoding xyloglucan enzymes were regulated transcriptionally and epigenetically during ripening. ABA treatment enhanced color development and ripening. GO analysis of DEGs in the RNA-seq of the ABA treatment revealed expression variations in genes encoding members of the Aux/IAA and ARF families. In the WGBS, genes encoding enzymes of the cytokinin biosynthesis had differential DNA methylation after the ABA treatment. Our work shows the genetic factors modulated by ABA at the genetic and epigenetic levels during non-climacteric ripening.
Investigating the conformational landscape of AlphaFold2-predicted protein kinase structures
Authors: Al-Masri Carmen , Trozzi Francesco , Patek Marcel , Cichońska Anna , Ravikumar Balaguru , Rahman Rayees 
Published: December 2022

AbstractProtein kinases are a family of signalling proteins, crucial for maintaining cellular homeostasis. When dysregulated, kinases drive the pathogenesis of several diseases, and are thus one of the largest target categories for drug discovery. Kinase activity is tightly controlled by switching through several active and inactive conformations in their catalytic domain. Kinase inhibitors have been designed to engage kinases in specific conformational states, where each conformation presents a unique physico-chemical environment for therapeutic intervention. Thus, modeling kinases across conformations can enable the design of novel and optimally selective kinase drugs. Due to the recent success of AlphaFold2 in accurately predicting the 3D structure of proteins based on sequence, we investigated the conformational landscape of protein kinases as modeled by AlphaFold2. We observed that AlphaFold2 is able to model several kinase conformations across the kinome, however, certain conformations are only observed in specific kinase families. Furthermore, we show that the per residue predicted local distance difference test can capture information describing conformational dynamics of kinases. Finally, we evaluated the docking performance of AlphaFold2 kinase structures for enriching known ligands. Taken together, we see an opportunity to leverage AlphaFold2 models for structure-based drug discovery against kinases across several pharmacologically relevant conformational states.
Cell-Sized Lipid Vesicles as Artificial Antigen-Presenting Cells for Antigen-Specific T Cell Activation
Authors: Chen Jui-Yi , Agrawal Sudhanshu , Yi Hsiu-Ping , Vallejo Derek , Agrawal Anshu , Lee Abraham 
Published: December 2022

AbstractIn this study, efficient T cell activation is demonstrated using cell-sized artificial antigen-presenting cells (aAPCs) with protein-conjugated bilayer lipid membranes that mimic biological cell membranes. The highly uniform aAPCs are generated by a facile method based on standard droplet microfluidic devices. These aAPCs are able to activate the T cells in peripheral blood mononuclear cells (PBMCs), showing a 28-fold increase in IFNγ secretion, a 233-fold increase in antigen-specific CD8 T cells expansion, and a 16-fold increase of CD4 T cell expansion. The aAPCs do not require repetitive boosting or additional stimulants and can function at a relatively low aAPC-to-T cell ratio (1-to-17). The research presents strong evidence that the surface fluidity and size of the aAPCs are critical to the effective formation of immune synapses essential for T cell activation. The findings demonstrate that the microfluidic-generated aAPCs can be instrumental in investigating the physiological conditions and mechanisms for T cell activation. Finally, this method demonstrates the feasibility of customizable aAPCs for a cost-effective off-the-shelf approach to immunotherapy.
Ovule cell wall composition is a maternal determinant of grain size in barley
Authors: Yang Xiujuan , Wilkinson Laura G. , Aubert Matthew K. , Houston Kelly , Shirley Neil J. , Tucker Matthew R. 
Published: December 2022

SummaryIn cereal species, seed and grain size is influenced by growth of the ovule integuments (seed coat), the spikelet hull (lemma and palea) and the filial endosperm. It has remained unclear whether a highly conserved ovule tissue, the nucellus, has any impact on grain size.Immunolabelling revealed that the barley nucellus comprises two distinct cell types that differ in terms of cell wall homogalacturonan (HG) accumulation. Transcriptional profiling of the nucellus identified two pectin methylesterase genes,OVULE PECTIN MODIFIER 1(OPM1) andOPM2, which are expressed in the ovule but absent from the seed.Ovules from anopm1 opm2mutant, and plants expressing an ovule-specific pectin methylesterase inhibitor (PMEI), exhibit reduced HG accumulation. This results in changes to ovule cell size and shape, and ovules that are longer than wild-type controls. At grain maturity, this is manifested as significantly longer grain.These findings indicate that cell wall composition during ovule development acts to limit ovule and seed growth. The investigation of ovule PME and PMEI activity reveals an unexpected role of maternal tissues in controlling grain growth prior to fertilisation, one that has been lacking from models exploring improvements in grain size.
Type I Interferon Signaling on Antigen-Presenting Cells Blunts Cell-Mediated Immunity TowardListeria monocytogenes
Authors: Morrow Zachary T. , Sauer John-Demian 
Published: December 2022

AbstractListeria monocytogenesis a facultative intracellular pathogen that has been used for decades to understand mechanisms of bacterial pathogenesis and both innate and adaptive immunity.L. monocytogenesis a potent activator of CD8+T-cell mediated immunity. Yet how the innate immune response to infection modulates CD8+T-cell responses is incompletely understood. Here, we utilize an attenuatedL. monocytogenesvaccine platform to understand the impact of two innate immune pathways, type I interferon and inflammasomes, on CD8+T-cell responses using a combination of mutant mice and genetically engineeredL. monocytogenes. IFNAR−/−mice had the most robust T-cell response, while Caspase-1−/−mice were not different from WT. We uncover a role for inflammasomes in the absence of type I interferon as Caspase-1−/−/IFNAR−/−mice had fewer T-cells than IFNAR−/−. IFNAR−/−had more than twice as many memory precursors, promoting enhanced protection from rechallenge. Importantly, increased memory precursor T-cell abundance did not come at the expense of short-lived effectors. Vaccines genetically modified to induce lower type I interferon production yielded enhanced T-cell responses. Deficits from type I interferon signaling are dendritic cell-intrinsic, rather than acting on T-cells, as IFNAR−/−dendritic cells induced two-fold more T-cell proliferation than WT inex vivoT-cell proliferation assays. Thus, modulating type I IFN signaling during vaccination may lead to more potent T-cell-based vaccines. Importantly, this suggests innate immune signaling significantly impacts the CD8+T-cell response and suggests CD8+T-cell quantity and quality are important factors to consider during rational vaccine design.
Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein
Authors: Stelfox Alice J. , Oguntuyo Kasopefoluwa Y. , Rissanen Ilona , Harlos Karl , Rambo Robert , Lee Benhur , Bowden Thomas A. 
Published: December 2022

AbstractIncreased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the presence of a receptor-binding protein, RBP, which facilitates host-cell attachment and plays a fundamental role in determining host-range. Here, we study the RBP presented on the surface of rodent-borne paramyxoviruses Mossman and Nariva (MosV and NarV, respectively), viruses that constitute founding members of the recently definedNarmovirusgenus within theParamyxoviridaefamily. Crystallographic analysis of the C-terminal head region of the dimeric MosV and NarV RBPs demonstrates that while these glycoproteins retain the canonical six-bladed β-propeller fold found in other paramyxoviral RBPs, they lack the structural motifs associated with established paramyxovirus host-cell receptor entry pathways. Consistent with MosV-RBP and NarV-RBP undergoing a distinct entry pathway from other characterized paramyxoviruses, structure-based phylogenetic analysis demonstrates that these six-bladed β-propeller head domains form a singular structural class that is distinct from other paramyxoviral RBPs. Additionally, using an integrated crystallographic and small angle X-ray scattering analysis, we confirm that MosV-RBP and NarV-RBP form homodimeric arrangements that are distinct from those adopted by other paramyxovirus RBPs. Altogether, this investigation provides a molecular-level blueprint of the narmovirus RBP that broadens our understanding of the structural space and functional diversity available to paramyxovirus RBPs.ImportanceGenetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genusNarmovirus, familyParamyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely a six-bladed β-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses.
Divisively normalized neuronal processing of uncertain visual feedback for visuomotor learning
Authors: Makino Yuto , Hayashi Takuji , Nozaki Daichi 
Published: December 2022

AbstractWhen encountering a visual error during a reaching movement, the motor system improves the motor command for the subsequent trial. The degree of improvement is well-known to be degraded with visual error uncertainty, which is considered evidence that the motor system optimally estimates the error. However, it remains unclear how such statistical computation is accomplished. Here, we propose an alternative motor learning scheme implemented with a divisive normalization (DN) mechanism. This scheme assumes that when an uncertain visual error is provided by multiple cursors, the motor system processes the error conveyed by each cursor and integrates the information using DN. The DN scheme can reproduce the patterns of learning response when 1, 2, or 3 cursors are concurrently displayed and predict how the increase in the visual error uncertainty degrades the learning response. Our proposed scheme provides a novel view of how the motor learning system updates the motor command according to uncertain visual error information.
Time scales of human mpox transmission in the Netherlands
Authors: Miura Fuminari , Backer Jantien A. , van Rijckevorsel Gini , Bavalia Roisin , Raven Stijn , Petrignani Mariska , Ainslie Kylie E. C. , Wallinga Jacco ,   the Dutch Mpox Response Team
Published: December 2022

AbstractMpox has spread rapidly to many countries in non-endemic regions. After reviewing detailed exposure histories of 109 pairs of mpox cases in the Netherlands, we identified 34 pairs where transmission was likely and the infectee reported a single potential infector with a mean serial interval of 10.1 days (95% CI: 6.6–14.7 days). Pre-symptomatic transmission may have occurred in five out of eighteen pairs. These findings emphasize that precaution remains key, regardless of the presence of recognizable symptoms of mpox.
Detection of Left Ventricular Systolic Dysfunction from Single-Lead Electrocardiography Adapted for Wearable Devices
Authors: Khunte Akshay , Sangha Veer , Oikonomou Evangelos K , Dhingra Lovedeep S , Aminorroaya Arya , Mortazavi Bobak J , Coppi Andreas , Krumholz Harlan M , Khera Rohan 
Published: December 2022

ABSTRACTArtificial intelligence (AI) can detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs). Wearable devices could allow for broad AI-based screening but frequently obtain noisy ECGs. We report a novel strategy that automates the detection of hidden cardiovascular diseases, such as LVSD, adapted for noisy single-lead ECGs obtained on wearable and portable devices. Overall, 385,601 ECGs were used for development of a standard and noise-adapted model. For the noise-adapted model, ECGs were augmented during training with random gaussian noise within four distinct frequency ranges, each emulating real-world noise sources. Both models performed comparably on clean ECGs with an AUROC of 0.90. The noise-adapted model performed significantly better on the same test set augmented with four distinct real-world noise recordings at multiple signal-to-noise ratios (SNRs), including noise isolated from a portable device ECG. The standard and noise-adapted models had an AUROC of 0.72 and 0.87, respectively when evaluated on ECGs augmented with portable ECG device noise at an SNR of 0.5. This approach represents a novel strategy for the development of wearable adapted tools from clinical ECG repositories.
The kinematics of 3D arm movements in sub-acute stroke: impaired inter-joint coordination caused by both weakness and flexor synergy intrusion
Authors: Avni Inbar , Arac Ahmet , Binyamin-Netser Reut , Kramer Shilo , Krakauer John W. , Shmuelof Lior 
Published: December 2022

AbstractIt has long been of interest to characterize the components that generate the motor control abnormalities in the arm after stroke. One approach has been to decompose the hemiparesis phenotype into negative signs, such as weakness, and positive signs, such as intrusion of synergies. Here, we sought to identify the contributions of weakness and the flexor synergy to motor function and impairment, as defined by kinematic and clinical scales, respectively, in sub-acute stroke using two 3D arm tasks that differed in their requirement for elbow extension. Thirty-three sub-acute post-stroke participants and sixteen healthy controls performed a cup-to-mouth task, requiring shoulder and elbow flexion (within flexor synergy), and a reaching task, requiring shoulder flexion and elbow extension (out of flexor synergy). Using markerless 3D pose-estimation, we analyzed upper limb kinematics to assess overall task performance and intrusion of pathological synergies. Weakness was measured using a grip dynamometer. Performance in both tasks was impaired to a similar degree in the stroke participants compared to controls. Subsequent analysis of coordination patterns between the elbow and the shoulder joints revealed intrusion of synergies in the reaching task based on the time spent within a flexion-flexion pattern (flexor synergy proportion) and the correlation between shoulder and elbow angles when the shoulder was flexing (flexion synergy strength). Regression analysis indicated that the significant predictors of poor task performance were weakness and flexor synergy intrusion. Notably, the Fugl-Meyer Assessment was abnormal even when just weakness caused the impairment, which means that caution is required when using this scale to quantify synergies. We conclude that both weakness and synergy intrusion contribute to impaired coordination of the elbow and shoulder joints in the sub-acute post-stroke period. This study shows that careful kinematic analysis of naturalistic movements is required to better characterize the components of upper limb impairment after stroke.
The developmental basis for scaling of mammalian tooth size
Authors: Christensen Mona M. , Hallikas Outi , Roy Rishi Das , Väänänen Vilma , Stenberg Otto E. , Häkkinen Teemu J. , François Jean-Christophe , Asher Robert J. , Klein Ophir D. , Holzenberger Martin , Jernvall Jukka 
Published: December 2022

ABSTRACTWhen evolution leads to differences in body size, organs generally scale along. A well-known example of the tight relationship between organ and body size is the scaling of mammalian molar teeth. To investigate how teeth scale during development and evolution, we compared molar development in mouse and rat from initiation through final size. Whereas the linear dimensions of the rat first lower molar are twice that of the mouse molar, their shapes are largely the same. We found that scaling of the molars starts early, and that the rat molar is patterned equally as fast but in a larger size than the mouse molar. Using transcriptomics, we discovered that a known regulator of body size, insulin-like growth factor 1 (Igf1), is more highly expressed in the rat molars compared to the mouse molars.Ex vivoandin vivomouse models demonstrated that modulation of the IGF pathway reproduces several aspects of the observed scaling process. Furthermore, analysis of IGF1-treated mouse molars and computational modeling indicate that IGF signaling scales teeth by simultaneously enhancing growth and by inhibiting the cusp patterning program, thereby providing a relatively simple mechanism for scaling teeth during development and evolution. Finally, comparative data from shrews to elephants suggest that this scaling mechanism regulates the minimum tooth size possible, as well as the patterning potential of large teeth.