bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision MRI Phenotyping Enables Detection of Small Changes in Body Composition for Longitudinal Cohorts
Authors: Whitcher Brandon , Thanaj Marjola , Cule Madeleine , Liu Yi , Basty Nicolas , Sorokin Elena P. , Bell Jimmy D. , Thomas E. Louise 
Published: August 2021

ABSTRACTLongitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease. Here we investigate changes in body composition in 3,088 free-living participants, part of the UK Biobank in-depth imaging study. All participants underwent neck-to-knee MRI scans at the first imaging visit and after approximately two years (second imaging visit). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline, including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), as well as fat and iron content in liver, pancreas and spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanning interval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, but statistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in the thighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting for disease status at the first imaging visit did not have an additional impact on the changes observed. In summary, we show that even after a relatively short period of time significant changes in body composition can take place, probably reflecting the obesogenic environment currently inhabited by most of the general population in the United Kingdom.
Task-related, intrinsic oscillatory and aperiodic neural activity predict performance in naturalistic team-based training scenarios
Authors: Cross Zachariah R. , Chatburn Alex , Melberzs Lee , Temby Philip , Pomeroy Diane , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina 
Published: August 2021

AbstractEffective teams are essential for optimally functioning societies. However, little is known regarding the neural basis of two or more individuals engaging cooperatively in real-world tasks, such as in operational training environments. In this exploratory study, we recruited forty individuals paired as twenty dyads and recorded dual-EEG at rest and during realistic training scenarios of increasing complexity using virtual simulation systems. We estimated markers of intrinsic brain activity (i.e., individual alpha frequency and aperiodic activity), as well as task-related theta and alpha oscillations. Using nonlinear modelling and a logistic regression machine learning model, we found that resting-state EEG predicts performance and can also reliably differentiate between members within a dyad. Task-related theta and alpha activity during easy training tasks predicted later performance on complex training to a greater extent than prior behaviour. These findings complement laboratory-based research on both oscillatory and aperiodic activity in higher-order cognition and provide evidence that theta and alpha activity play a critical role in complex task performance in team environments.
Real-Time Brain-Machine Interface Achieves High-Velocity Prosthetic Finger Movements using a Biologically-Inspired Neural Network Decoder
Authors: Willsey Matthew S. , Nason Samuel R. , Ensel Scott R. , Temmar Hisham , Mender Matthew J. , Costello Joseph T. , Patil Parag G. , Chestek Cynthia A. 
Published: August 2021

AbstractDespite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. The algorithm that converts brain signals to a control signal for the prosthetic device is one of the limitations in achieving rapid and realistic finger movements. To achieve more realistic finger movements, we developed a shallow feed-forward neural network, loosely inspired by the biological neural pathway, to decode real-time two-degree-of-freedom finger movements. Using a two-step training method, a recalibrated feedback intention–trained (ReFIT) neural network achieved a higher throughput with higher finger velocities and more natural appearing finger movements than the ReFIT Kalman filter, which represents the current standard. The neural network decoders introduced herein are the first to demonstrate real-time decoding of continuous movements at a level superior to the current state-of-the-art and could provide a starting point to using neural networks for the development of more naturalistic brain-controlled prostheses.
Conservation and divergence of poly(A) tail regulation during the mammalian oocyte-to-embryo transition
Authors: Liu Yusheng , Jin Junxue , Zhang Yiwei , Wang Le-Yun , Zhang Chuanxin , Hou Zhenzhen , Li Wei , Liu Zhonghua , Lu Falong , Wang Jiaqiang 
Published: August 2021

SUMMARYPoly(A) tail length and non-A residues are vital for oocyte-to-embryo transition (OET) in mice and humans1–5. However, the role of poly(A) tail length and non-A residues during OET in other commonly used mammalian animal models for human diseases remains unexplored. In addition, the degree of conservation in maternal mRNA poly(A) tail dynamics during OET across different mammal species is unknown. Here, we conduct a comparative analysis of the poly(A) tails during OET across four species: mice, rats, pigs, and humans. Dynamics during OET found to be conserved across all four species include: maternal mRNA deadenylation during oocyte maturation and re-polyadenylation after fertilization; a fall-rise trend in poly(A) tail length distribution; a rise-fall trend in the ratio of poly(A) tails with non-A residues; higher abundance of non-A residues in poly(A) tails of maternal mRNA than in zygotic genome activation (ZGA) mRNA; maternal mRNA with U residues degrades faster than those without U residues at the stage when ZGA takes place. While in mice and rats maternal mRNA deadenylation is impaired in parthenogenetic embryos and ZGA inhibition leads to blocked maternal mRNA deadenylation in mice and humans. In contrast, the length of consecutive U residues and the duration time of U residues in poly(A) tail diverges across the four species. Together, these findings reveal that the poly(A) tail mediated maternal mRNA post-transcriptional regulation is highly conserved in mammals with unique divergences in the length and life-span of U residues, providing new insights for the further understanding of OET across different mammals.
Dynamics of mitochondrial mRNA abundance and poly(A) tail during the mammalian oocyte-to-embryo transition
Authors: Liu Yusheng , Zhang Yiwei , Liu Zhonghua , Lu Falong , Wang Jiaqiang 
Published: August 2021

AbstractMitochondria are responsible for producing a cell’s energy and play a central role in many metabolic tasks, as well as signaling transduction and cell death1. Mitochondria dysfunctions cause several human diseases and aging processes2–8. Mammalian oocytes contain far more mitochondria than somatic cells. The nuclear localization of mitochondrial tricarboxylic acid cycle (TCA) cycle enzymes, which normally localize in the mitochondria, is critical for zygotic genome activation (ZGA) and the oocyte-to-embryo transition (OET) in mice9. However, during the mammalian OET, the abundance and post-transcriptional regulation of mitochondrial mRNA (MT-mRNA), particularly the poly(A) tail, has never been studied. Here, we used two independent sequencing methods (PAIso-seq1 and PAIso-seq2) to describe the features of MT-mRNA in mouse cell lines, thirteen mouse tissues and during the OET in mouse, rat, pig, and humans. These features included expression abundance, poly(A) tail length, and non-A residues in poly(A) tails. Unlike nuclear mRNA, we discovered that MT-mRNA has a stable distribution pattern of poly(A) tail length in different cell lines, across tissues, and during mammalian OET. MT-mRNA possesses non-A residues in the poly(A) tail (non-A residues hereafter), which change slightly across tissues and during the OET. We also found that the abundance of MT-mRNA varies substantially across tissues, increases during the OET, and increases along major ZGA in mice, rats, pigs, and humans. These findings provide insights into changes in MT-mRNA abundance and poly(A) tail during the mammalian OET and provide a resource for future studies on the posttranscriptional regulation of mitochondrial transcripts.
Abundant non-A residues in the poly(A) tail orchestrate the mouse oocyte-to-embryo transition
Authors: Liu Yusheng , Nie Hu , Wang Le-Yun , Wu Shuang , Li Wei , Zhou Qi , Wang Jiaqiang , Lu Falong 
Published: August 2021

AbstractNon-A (U, G, and C) residues can be added to the 5’-end, internal, and 3’-end positions of poly(A) tails of RNA transcripts1–3, and some of these have been shown to regulate mRNA stability4, 5. The mammalian oocyte-to-embryo transition (OET) relies on post-transcriptional regulation of maternal RNA, because transcription is silent during this process until the point of zygotic genome activation (ZGA)6–9. Although the regulation of mRNA translation by poly(A) tail length plays an important role in the mammalian OET, the dynamics and functions of non-A residues in poly(A) tails are completely unknown. In this study, we profiled the genome-wide presence, abundance, and roles of non-A residues during the OET in mice using PAIso-seq1 and PAIso-seq22, 10, two complementary methods of poly(A) tail analysis. We found that non-A residues are highly dynamic in maternal mRNA, following a general pattern of beginning to increase at the MII stage, becoming highly abundant after fertilization with U residues in about half of poly(A) tails in 1-cell embryos, and declining in 2-cell embryos. We revealed that Btg4-mediated global maternal mRNA deadenylation created the substrates for U residue addition by Tut4/7 at their 3’-ends and further re-polyadenylation. In addition, G residues can be added by Tent4a/b. Finally, we demonstrate that G residues stabilize the modified mRNA, while the U residues mark maternal RNA for faster degradation in 2-cell mouse embryos. Taken together, these findings demonstrate that non-A residues are abundant and re-sculpt the maternal transcriptome to initiate zygotic development, which reveals the functional importance of the post-transcriptional regulation mediated by non-A residues in mRNA poly(A) tails.
Cross-frequency slow oscillation–spindle coupling in a biophysically realistic thalamocortical neural mass model
Authors: Jajcay Nikola , Cakan Caglar , Obermayer Klaus 
Published: August 2021

AbstractSleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often timelock and are implicated in the memory formation. Here, we analyze a neural mass model of the thalamocortical loop of which the cortical node can generate slow oscillations (approx. 1 Hz) while its thalamic component can generate fast sleep spindles of σ-band activity (12–15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic node’s potassium leak and anomalous rectifying currents, and for different parameter regimes of the cortical node. The latter are: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced σ-band activity in the cortical node, however, is typically strongest during the UP state, which follows a DOWN state “window of opportunity” for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.
The polyglutamine amyloid nucleus in living cells is a monomer with competing dimensions of order
Authors: Kandola Tej , Venkatesan Shriram , Zhang Jiahui , Lerbakken Brooklyn , Blanck Jillian F , Wu Jianzheng , Unruh Jay , Berry Paula , Lange Jeffrey J. , Von Schulze Alex , Box Andrew , Cook Malcolm , Sagui Celeste , Halfmann Randal 
Published: August 2021

AbstractA long-standing goal of the study of amyloids has been to characterize the structural basis of the rate-determining nucleating event. However, the ephemeral nature of that event has made it inaccessible to classical biochemistry, structural biology, and computational approaches. Here, we addressed that limitation by measuring the dependence of amyloid formation on concentration and conformational templates in living cells, whose volumes are sufficiently small to resolve the outcomes of independent nucleation events. We characterized numerous rationally designed sequence variants of polyglutamine (polyQ), a polypeptide that precipitates Huntington’s and other amyloid-associated neurodegenerative diseases when its length exceeds a characteristic threshold. This effort uncovered a pattern of approximately twelve Qs, only for polypeptides exceeding the clinical length threshold, that allow for amyloid nucleation to occur spontaneously within single polypeptides. Nucleation was inhibited by intermolecular phase separation. Using atomistic molecular dynamics simulations, we found that the pattern encodes a minimal steric zipper of interdigitated side chains. Lateral growth of the steric zipper competed with axial growth to produce “pre-amyloid” oligomers. By illuminating the structural mechanism of polyQ amyloid formation in cells, our findings reveal a potential molecular etiology for polyQ diseases, and may provide a roadmap for the design of new therapies.
Simpler and Faster Development of Tumor Phylogeny Pipelines
Authors: Ali Sarwan , Ciccolella Simone , Lucarella Lorenzo , Vedova Gianluca Della , Patterson Murray 
Published: August 2021

AbstractIn the recent years there has been an increasing amount of single-cell sequencing (SCS) studies, producing a considerable number of new datasets. This has particularly affected the field of cancer analysis, where more and more papers are published using this sequencing technique that allows for capturing more detailed information regarding the specific genetic mutations on each individually sampled cell.As the amount of information increases, it is necessary to have more sophisticated and rapid tools for analyzing the samples. To this goal we developed plastic, an easy-to-use and quick to adapt pipeline that integrates three different steps: (1) to simplify the input data; (2) to infer tumor phylogenies; and (3) to compare the phylogenies.We have created a pipeline submodule for each of those steps, and developed new in-memory data structures that allow for easy and transparent sharing of the information across the tools implementing the above steps.While we use existing open source tools for those steps, we have extended the tool used for simplifying the input data, incorporating two machine learning procedures — which greatly reduce the running time without affecting the quality of the downstream analysis. Moreover, we have introduced the capability of producing some plots to quickly visualize results.
SHED-dependent oncogenic signalling of the PEAK3 pseudo-kinase
Authors: Ounoughene Youcef , Fourgous Elise , Boublik Yvan , Saland Estelle , Guiraud Nathan , Recher Christian , Urbach Serge , Fort Philippe , Sarry Jean-Emmanuel , Fesquet Didier , Roche Serge 
Published: August 2021

ABSTRACTThe PEAK1 and pragmin/PEAK2 pseudo-kinases have emerged as important components of the protein tyrosine kinase pathway implicated in cancer progression. They can signal by a scaffolding mechanism that involves a conserved split helical dimerization (SHED) module. We recently identified PEAK3 as a novel member of this family based on structural homology; however, its signalling mechanism remains unclear. Here, we found that although it can self-associate, PEAK3 shows higher evolutionary divergence than PEAK1/2. Moreover, PEAK3 protein is strongly expressed in human haematopoietic cells, and is upregulated in acute myeloid leukaemia. Functionally, PEAK3 overexpression in U2OS sarcoma cells enhanced their growth and migratory properties, while its silencing in THP1 leukemic cells reduced these effects. Importantly, an intact SHED module was required for these PEAK3 oncogenic activities. Mechanistically, through a phosphokinase survey, we identified PEAK3 as a novel inducer of AKT signalling, independent of growth factor stimulation. Then, proteomic analyses revealed that PEAK3 interacts with the signalling proteins GRB2 and ASAP1/2 and the protein kinase PYK2, and that these interactions require the SHED domain. Moreover, PEAK3 activated PYK2 to promote AKT signalling. Thus, the PEAK1-3 pseudo-kinases may use a conserved SHED-dependent mechanism to activate specific signalling proteins to promote oncogenesis.
Beyond RuBisCO: Convergent molecular evolution of multiple chloroplast genes in C4 plants
Authors: Casola Claudio , Li Jingjia 
Published: August 2021

AbstractBackgroundThe recurrent evolution of the C4 photosynthetic pathway in angiosperms represents one of the most extraordinary examples of convergent evolution of a complex trait. Comparative genomic analyses have unveiled some of the molecular changes associated with the C4 pathway. For instance, several key enzymes involved in the transition from C3 to C4 photosynthesis have been found to share convergent amino acid replacements along C4 lineages. However, the extent of convergent replacements potentially associated with the emergence of C4 plants remains to be fully assessed. Here, we introduced a robust empirical approach to test molecular convergence along a phylogeny including multiple C3 and C4 taxa. By analyzing proteins encoded by chloroplast genes, we tested if convergent replacements occurred more frequently than expected in C4 lineages compared to C3 lineages. Furthermore, we sought to determine if convergent evolution occurred in multiple chloroplast proteins beside the well-known case of the large RuBisCO subunit encoded by the chloroplast gene rbcL.MethodsOur study was based on the comparative analysis of 43 C4 and 21 C3 grass species belonging to the PACMAD clade, a focal taxonomic group in many investigations of C4 evolution. We first used protein sequences of 67 orthologous chloroplast genes to build an accurate phylogeny of these species. Then, we inferred amino acid replacements along 13 C4 lineages and 9 C3 lineages using reconstructed protein sequences of their ancestral branches, corresponding to the most recent common ancestor of each lineage. Pairwise comparisons between ancestral branches allowed us to identify both convergent and divergent amino acid replacements between C4-C4, C3-C3 and C3-C4 lineages.ResultsThe reconstructed phylogenetic tree of 64 PACMAD grasses was characterized by strong supports in all nodes used for analyses of convergence. We identified 217 convergent replacements and 201 divergent replacements in 45/67 chloroplast proteins in both C4 and C3 ancestral branches. Pairs of C4-C4 ancestral branches showed higher levels of convergent replacements than C3-C3 and C3-C4 pairs. Furthermore, we found that more proteins shared unique convergent replacements in C4 lineages, with both RbcL and RpoC1 (the RNA polymerase beta’ subunit 1) showing a significantly higher convergent/divergent replacements ratio in C4 branches. Notably, significantly more C4-C4 pairs of ancestral branches showed higher numbers of convergent vs. divergent replacements than C3-C3 and C3-C4 pairs. Our results demonstrated that, in the PACMAD clade, C4 grasses experienced higher levels of molecular convergence than C3 species across multiple chloroplast genes. These findings have important implications for both our understanding of the evolution of photosynthesis and the goal of engineering improved crop varieties that integrates components of the C4 pathway.
Predictive coding during action observation - a depth-resolved intersubject functional correlation study at 7T
Authors: Cerliani Leonardo , Bhandari Ritu , De Angelis Lorenzo , van der Zwaag Wietske , Bazin Pierre-Louis , Gazzola Valeria , Keysers Christian 
Published: August 2021

AbstractWhile the brain regions involved in action observation are relatively well documented in humans and primates, how these regions communicate to help understand and predict actions remains poorly understood. Traditional views emphasized a feed-forward architecture in which visual features are organized into increasingly complex representations that feed onto motor programs in parietal and then premotor cortices where the matching of observed actions upon the observer’s own motor programs contributes to action understanding. Predictive coding models place less emphasis on feed-forward connections and propose that feed-back connections from premotor regions back to parietal and visual neurons represent predictions about upcoming actions that can supersede visual inputs when actions become predictable, with visual input then merely representing prediction errors. Here we leverage the notion that feed-back connections target specific cortical layers to help adjudicate across these views. Specifically, we test whether observing sequences of hand actions in their natural order, which permits participants to predict upcoming actions, triggers more feed-back input to parietal regions than seeing the same actions in a scrambled sequence that hinders making predictions. Using submillimeter fMRI acquisition at 7T, we find that watching predictable sequences triggers more action-related activity (as measured using intersubject functional correlation) in the parietal cortical area PFt at depths receiving feed-back connections (layers III and V/VI) than watching the exact same actions in scrambled and hence unpredictable sequence. In addition, functional connectivity analysis performed using intersubject functional connectivity confirms that these increased action-related signals in PFt could originate from ventral premotor region BA44. This data showcases the utility of intersubject functional correlation in combination with 7T MRI to explore the architecture of social cognition under more naturalistic conditions, and provides evidence for models that emphasize the importance of feed-back connections in action prediction.