bluuebunny/crossref_metadata_2025_split huggingface dataset:
The perpendicular gyroscope: modal analysis of plate, beam and gyroscope multistructures
Authors: Madine K. H. , Colquitt D. J. 
Published: August 2024

This paper presents a study of the perpendicular gyroscope, which is formed of two orthogonal beams, a flexural plate and a gyroscope. Two sets of chiral-torsional boundary conditions are derived to analytically model the dynamic effects of the gyroscope while taking into account the broken symmetries of the system. The perpendicular junction causes the coupling of the compressional, flexural and torsional displacements in the system. This complex behaviour is accounted for with a comprehensive set of kinematic and dynamic junction conditions. Modal analysis demonstrates the fully coupled system and reveals how the spinning gyroscope induces dynamic chiral Chladni patterns in the plate.
This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 2)’.
Time trends in cardiac doses in 10,000 patients receiving curative thoracic radiation therapy between 2009 and 2020
Authors: Forbes Nora , Terrones-Campos Cynthia , Smith Abraham , Reekie Joanne , Darkner Sune , Maraldo Maja , Pøhl Mette , Risumlund Signe , Specht Lena , Bentzen Soren M. , Petersen Jens , Vogelius Ivan R. 
Published: August 2024

AbstractBackground and purposeIn the last 20 years, it has become well-documented that incidental cardiac exposure to ionizing radiation is associated with a clinically relevant increased risk of cardiovascular morbidity. In parallel, radiation therapy technologies have been developed to provide target dose coverage with less exposure to adjacent organs at risk. In the current work, we investigate trends in cardiac exposure among patients treated with curative intent radiotherapy from a single institution between 2009 to 2020.Materials and methods10,215 treatment courses were analyzed from 9,966 patients treated with curative intent for intrathoracic or breast cancers in the period 2009-2020. All hearts were re-delineated using an AI model to ensure consistency over time. Cardiac doses were extracted in 3D from the record-and-verify system and converted, voxel-by-voxel, to equi-effective doses in 2 Gy fractions (EQD2) using α/β=2 Gy. Mean heart dose (in EQD2) and volume exposed to 5 and 40 Gy (V5 and V40Gy), respectively, were extracted. Time trends in these cardiac dose-volume metrics were investigated for each diagnosis.ResultsPatients with esophageal cancer had the highest mean heart dose (median = 11.67 Gy; IQR = 2.85, 18.18), while the lowest was observed in patients with breast cancer (median = 0.60 Gy; IQR = 0.30, 1.08) and lymphoma (median = 0.01 Gy; IQR = 0.00, 0.38). A decreasing trend over time was seen most clearly for patients with esophageal and lung cancers (p<0.05). Among patients with breast cancer, V40 decreased from 2009-2015 after which we observed an increase.ConclusionThere has been a significant reduction in radiation exposure to the heart in patients treated in the period 2009-2020, likely due to increased awareness of cardiovascular toxicity and technological developments. The study also found a significant increase in V40 from 2015 to 2020 for patients with breast cancers, possibly related to increased prioritization of target coverage.Highlights10,215 radiation therapy plans extracted and analyzedHearts were re-delineated with machine learning on the therapy CT-scan to ensure time-independent delineationsCardiac doses were found to decrease over time, especially high dose exposure of intrathoracic lesionsAn unexpected increase in cardiac high dose volume (V40Gy) for breast cancer treatment plans in recent years was observed
Nearly complete genome assembly of a critically endangered pine illuminates evolution and conservation of conifers
Authors: Zhang Ren-Gang , Liu Hui , Shu Heng , Liu De-Tuan , Shang Hong-Yun , Jia Kai-Hua , Wang Xiao-Quan , Sun Wei-Bang , Zhao Wei , Ma Yong-Peng 
Published: August 2024

AbstractConifers are dominant in most temperate and boreal forest ecosystems, and are the most widely distributed of the gymnosperms. Despite this, many conifer species are threatened with extinction, and in particular the genetic mechanisms underlying their endangerment remain largely unknown.Pinus squamata, which harbors an extremely large diploid genome and conservation significance, is among the 100 most endangered species (plants and animals) globally, and has been designated as ‘Critically Endangered’ on the IUCN Red List. In this study, we report an almost complete genome sequence forP. squamatagenerated by a suite of sequencing technologies, with an assembly of 29.2 Gb, a scaffold N50 length of 2.5 Gb, and a remarkable contig N50 length of 915.4 Mb. This represents the largest and most high-quality gymnosperm genome sequenced to date. The genome is characterized by an ultra-low rate of heterozygosity, is dominated by transposable elements, and contains 55,413 protein-coding genes. Our study provides the first detailed examination of chromosome organization inP. squamata, revealing Rabl configurations and distinctive centromere signatures. This genomic milestone not only deepens our understanding of gymnosperm genetics and evolution but also lays a solid foundation for the development of effective conservation measures, ensuring the survival of this rare species in the face of environmental challenges.
Modeling collagen fibril degradation as a function of matrix microarchitecture
Authors: Debnath B. , Narasimhan B. N. , Fraley S. I. , Rangamani P. 
Published: August 2024

AbstractCollagenolytic degradation is a process fundamental to tissue remodeling. The microarchitecture of collagen fibril networks changes during development, aging, and disease. Such changes to microarchitecture are often accompanied by changes in matrix degradability.In vitro, collagen matrices of the same concentration but different microarchitectures also vary in degradation rate. How do different microarchitectures affect matrix degradation? To answer this question, we developed a computational model of collagen degradation. We first developed a lattice model that describes collagen degradation at the scale of a single fibril. We then extended this model to investigate the role of microarchitecture using Brownian dynamics simulation of enzymes in a multi-fibril three dimensional matrix to predict its degradability. Our simulations predict that the distribution of enzymes around the fibrils is non-uniform and depends on the microarchitecture of the matrix. This non-uniformity in enzyme distribution can lead to different extents of degradability for matrices of different microarchitectures. Our model predictions were tested usingin vitroexperiments with synthesized collagen gels of different microarchitectures. Experiments showed that indeed degradation of collagen depends on the matrix architecture and fibril thickness. In summary, our study shows that the microarchitecture of the collagen matrix is an important determinant of its degradability.
Oligomerization-Mediated Phase-Separation in the Nucleoid-Associated Sensory Protein H-NS is Controlled by Ambient Cues
Authors: Lukose Bincy , Goyal Saloni , Naganathan Athi N. 
Published: August 2024

ABSTRACTH-NS, a nucleoid-associated protein (NAP) from enterobacteria, regulates gene expression by dynamically transducing environmental cues to conformational assembly and DNA binding. In this work, we show that H-NS fromEscherichia coli, which can assemble into octameric and tetrameric oligomerization states, forms spontaneous micron-sized liquid-like condensates with DNA at sub-physiological concentrationsin vitro. The heterotypic condensates are metastable at 298 K, partially solubilizing with time, while still retaining their liquid-like properties. The condensates display UCST-like phase behavior solubilizing at higher temperatures, but with a large decrease in droplet-assembly propensities at 310 K and also at higher ionic strength. Condensate formation can be tuned in a cyclic manner between 298 and 310 K with the extent of reversibility determined by the incubation time, highlighting strong hysteresis. An engineered phospho-mimetic variant (Y61E) of H-NS, which is dimeric and only weakly binds DNA, is unable to form condensates. The Y61E mutant solubilizes pre-formed H-NS condensates with DNA in a few minutes with nearly an order of magnitude speed-up in droplet dissolution at 310 K relative to 298 K, demonstrating rapid molecular transport between dilute and condensed phases. Our results establish that the oligomerization of H-NS is intrinsically tied not only to DNA binding but also its phase-separation tendencies, while showcasing the regulatable and programmable nature of heterotypic condensates formed by an archetypal NAP via multiple cues and their lifetimes.
Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling
Authors: Mcleod Jonathan C. , Lim Changhyun , Stokes Tanner , Sharif Jalil-Ahmad , Zeynalli Vagif , Wiens Lucas , D’Souza Alysha C , Colenso-Semple Lauren , McKendry James , Morton Robert W. , Mitchell Cameron J. , Oikawa Sara Y. , Wahlestedt Claes , Paul Chapple J , McGlory Chris , Timmons James A. , Phillips Stuart M. 
Published: August 2024

ABSTRACTA majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customised RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n=144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growthin vivo,while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, includingCYTOR– which was leukocyte-associated (FDR = 4.9 x10-7). Novel hypertrophy-linked ncRNAs includedPPP1CB-DT(myofibril assembly genes, FDR = 8.15 x 10-8), andEEF1A1P24andTMSB4XP8(vascular remodelling and angiogenesis genes, FDR = 2.77 x 10-5). We also discovered that hypertrophy lncRNAMYREMshows a specific myonuclear expression patternin vivo. Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways.One Sentence SummaryWe used an optimised transcriptomic strategy to identify a set of ncRNA genes regulated during skeletal muscle hypertrophy in one hundred and forty-four people, with network modelling and spatial imaging providing biological context.
Time Makes Space: Emergence of Place Fields in Networks Encoding Temporally Continuous Sensory Experiences
Authors: Wang Zhaoze , Di Tullio Ronald W. , Rooke Spencer , Balasubramanian Vijay 
Published: August 2024

AbstractThe vertebrate hippocampus is believed to use recurrent connectivity in area CA3 to support episodic memory recall from partial cues. This brain area also contains place cells, whose location-selective firing fields implement maps supporting spatial memory. Here we show that place cells emerge in networks trained to remember temporally continuous sensory episodes. We model CA3 as a recurrent autoencoder that recalls and reconstructs sensory experiences from noisy and partially occluded observations by agents traversing simulated arenas. The agents move in realistic trajectories modeled from rodents and environments are modeled as continuously varying, high-dimensional, sensory experience maps (spatially smoothed Gaussian random fields). Training our autoencoder to accurately pattern-complete and reconstruct sensory experiences with a constraint on total activity causes spatially localized firing fields, i.e., place cells, to emerge in the encoding layer. The emergent place fields reproduce key aspects of hippocampal phenomenology: a) remapping (maintenance of and reversion to distinct learned maps in different environments), implemented via repositioning of experience manifolds in the network’s hidden layer, b) orthogonality of spatial representations in different arenas, c) robust place field emergence in differently shaped rooms, with single units showing multiple place fields in large or complex spaces, and d) slow representational drift of place fields. We argue that these results arise because continuous traversal of space makes sensory experience temporally continuous. We make testable predictions: a) rapidly changing sensory context will disrupt place fields, b) place fields will form even if recurrent connections are blocked, but reversion to previously learned representations upon remapping will be abolished, c) the dimension of temporally smooth experience sets the dimensionality of place fields, including during virtual navigation of abstract spaces. Code for our experiments is available at1.
Serpina1e mediates the exercise-induced enhancement of hippocampal memory
Authors: Kim Hyunyoung , Shin Sanghee , Han Jeongho , Kim Jong-Seo , Park Hyungju 
Published: August 2024

AbstractThe exercise-induced enhancement of learning and memory is thought to be regulated by body□brain interactions via secretory proteins in the blood plasma1,2. Given the prominent role that skeletal muscle plays during exercise, the beneficial effects of exercise on cognitive functions appear to be mediated by muscle-derived secretory factors including myokines3,4. However, the specific myokines that exert beneficial effects on cognitive functions remain to be elucidated. Here, we reveal that a novel myokine, Serpina1e, acts a molecular mediator that directly supports long-term memory formation in the hippocampus. Using anin vivomyokine-labeling mouse model, proteomic analysis revealed that the Serpina1 family of proteins are the myokines whose levels increased the most in plasma after chronic aerobic exercise for 4 weeks. Systemic delivery of recombinant Serpina1e into sedentary mice was sufficient for reproducing the beneficial effect of exercise on hippocampus-associated cognitive functions. Moreover, plasma Serpina1e can cross the blood–cerebral spinal fluid (CSF) barrier and blood–brain barrier to reach the brain, thereby influencing hippocampal function. Indeed, an increase in the plasma level of Serpina1e promoted hippocampal neurogenesis, increased the levels of brain-derived neurotrophic factor (BDNF) and induced neurite growth. Our findings reveal that Serpina1e is a myokine that migrates to the brain and mediates exercise-induced memory enhancement by triggering neurotrophic growth signaling in the hippocampus. This discovery elucidates the molecular mechanisms underlying the beneficial effects of exercise on cognitive function and may have implications for the development of novel therapeutic interventions for alleviating cognitive disorders.
CaMutQC: An R Package for Integrative Quality Control of Cancer Somatic Mutations
Authors: Wang Xin , Jiang Tengjia , Shen Ao , Chen Yaru , Zhou Yanqing , Liu Jie , Zhao Shuhan , Chen Shifu , Ren Jian , Zhao Qi 
Published: August 2024

AbstractThe quality control and filtration of cancer somatic mutations (CAMs), including the elimination of false positives resulting from technical bias and the selection of key mutation candidates, is crucial for downstream analysis in cancer genomics. Due to diverse needs and the absence of standardized filtering criteria, the filtering strategies employed vary from study to study, often leading to reduced efficiency, accuracy, and comparability across similar analyses. Here we present CaMutQC, a heuristic quality control and soft-filtering R/Bioconductor package for CAMs. With CaMutQC, the removal of false positives, selection of potential mutation candidates, and Tumor Mutation Burden estimation can be executed in a single line of code, using default or customized parameters. A filter report and a code log generated after the filtration process assist with recording and comparison. The application of CaMutQC on a Whole-exome Sequencing (WES) benchmark dataset demonstrated its impressive capability by eliminating 85.55% of false positive mutations while retaining 90.72% of true positive mutations. Additionally, an extra 11.56% of true positive mutations were recused by the union strategy embedded in CaMutQC. CaMutQC is now available through Bioconductor athttps://bioconductor.org/packages/CaMutQC/under the GPL v3 license, and it will be updated regularly to incorporate top filtration strategy and parameter sets shared within the community.
Subsets of extraocular motoneurons produce kinematically distinct saccades during hunting and exploration
Authors: Dowell Charles K. , Hawkins Thomas , Bianco Isaac H. 
Published: August 2024

AbstractAnimals construct diverse behavioural repertoires by moving a limited number of body parts with varied kinematics and patterns of coordination. There is evidence that distinct movements can be generated by changes in activity dynamics within a common pool of motoneurons, or by selectively engaging specific subsets of motoneurons in a task-dependent manner. However, in most cases we have an incomplete understanding of the patterns of motoneuron activity that generate distinct actions and how upstream premotor circuits select and assemble such motor programmes. In this study, we used two closely related but kinematically distinct types of saccadic eye movement in larval zebrafish as a model to examine circuit control of movement diversity. In contrast to the prevailing view of a final common pathway, we found that in oculomotor nucleus, distinct subsets of motoneurons were engaged for each saccade type. This type-specific recruitment was topographically organised and aligned with ultrastructural differ-ences in motoneuron morphology and afferent synaptic innervation. Medially located motoneu-rons were active for both saccade types and circuit tracing revealed a type-agnostic premotor pathway that appears to control their recruitment. By contrast, a laterally located subset of motoneurons was specifically active for hunting-associated saccades and received premotor in-put from pretectal hunting command neurons. Our data support a model in which generalist and action-specific premotor pathways engage distinct subsets of motoneurons to elicit varied movements of the same body part that subserve distinct behavioural functions.
The BDNF/TrkB pathway in Somatostatin-expressing neurons suppresses cocaine-seeking behaviour
Authors: Didio Giuliano , Aitta-aho Teemu , Umemori Juzoh , Castrén Eero 
Published: August 2024

AbstractCocaine addiction is a highly debilitating condition consisting of compulsive self-administration and seek for the substance of abuse, and its most challenging feature is the high rate of relapse. Addiction and relapse share similarities with neural plasticity which acts through the Brain-Derived Neurotrophic Factor and its receptor TrkB. Somatostatin (SST) expressing interneurons are involved in neuronal plasticity and are important in modulating cocaine-seeking behaviour in mice. We tested the role of TrkB in Somatostatin (SST)-expressing neurons in the extinction of cocaine-seeking behaviour, using mice in which TrkB has been knocked out specifically in SST neurons. We have observed that in these mice, once a cocaine-conditioned place preference is acquired, its extinction through seven days of extinction training is impaired, showing how this process relies on neural plasticity in SST neurons. When we promoted plasticity during extinction training using a light-activable TrkB in SST neurons in the prefrontal cortex of cocaine-conditioned mice, relapse of cocaine-seeking was prevented. Our data identify the critical role of TrkB-mediated plasticity within SST neurons in the extinction of and relapse to cocaine addiction.
Perceived multisensory common cause relations shape the ventriloquism effect but only marginally the trial-wise aftereffect
Authors: Kayser Christoph , Heuer Herbert 
Published: August 2024

AbstractCombining multisensory cues is fundamental for perception and action, and reflected by two frequently-studied phenomena: multisensory integration and sensory recalibration. In the context of audio-visual spatial signals, these are exemplified by the ventriloquism effect and its aftereffect. The ventriloquism effect occurs when the perceived location of a sound is biased by a concurrent visual stimulus, while the aftereffect manifests as a recalibration of sound localization after exposure to spatially discrepant stimuli. The relationship between these processes—whether recalibration is a direct consequence of integration or operates independently—remains debated. This study investigates the role of causal inference in these processes by examining whether trial-wise judgments of audio-visual stimuli as originating from a common cause influence both the ventriloquism effect and the immediate aftereffect. Using a spatial paradigm, participants made explicit judgments about the common cause of stimulus pairs, and their influence on both perceptual biases was assessed. Our results indicate that while multisensory integration is contingent on common cause judgments, the immediate recalibration effect is not. This suggests that recalibration can occur independently of the perceived commonality of the multisensory stimuli, challenging the notion that recalibration is solely a byproduct of integration.