bluuebunny/crossref_metadata_2025_split huggingface dataset:
Near-Physiological in vitro Assembly of 50S Ribosomes Involves Parallel Pathways
Authors: Dong Xiyu , Doerfel Lili K. , Sheng Kai , Rabuck-Gibbons Jessica N. , Popova Anna M. , Lyumkis Dmitry , Williamson James R. 
Published: November 2022

ABSTRACTUnderstanding the assembly principles of biological macromolecular complexes remains a significant challenge, due to the complexity of the systems and the difficulties in developing experimental approaches. As a ribonucleoprotein complex, the ribosome serves as an ideal model system for the profiling of macromolecular complex assembly. In this work, we report an ensemble of large ribosomal subunit intermediate structures that accumulate during synthesis in a near-physiological and co-transcriptionalin vitroreconstitution system. Thirteen pre-50S intermediate maps covering the whole assembly process were resolved using cryo-EM single particle analysis and heterogeneous subclassification. Segmentation of the set of density maps reveals that the 50S ribosome intermediates assemble based on fourteen cooperative assembly blocks, including the smallest assembly core reported up to now, which is composed of a 600-nucleotide-long folded rRNA and three ribosomal proteins. The cooperative blocks assemble onto the assembly core following a defined set of dependencies, revealing the parallel assembly pathways at both early and late assembly stages of the 50S subunit.
Validation of predicted conformal intervals for prediction of human clinical pharmacokinetics
Authors: Fagerholm Urban , Alvarsson Jonathan , Hellberg Sven , Spjuth Ola 
Published: November 2022

ABSTRACTIntroductionConformal prediction (CP) methodology sits on top of machine learning methods and produces prediction confidence intervals that depend on how “strange” (non-conforming) test compounds are compared to training set compounds. CP has previously been successfully applied for prediction of steady-state volume of distribution (Vss) in humans, with 69 % of observations within the prediction interval at a 70 % confidence level. We have developed CP models for a variety of human pharmacokinetic (PK) parameters and validated their predictive accuracy (predictedvsobserved estimates), but not validated prediction confidence intervals for them. The main objective of this study was to predict 70 % confidence intervals for Vss, unbound fraction in plasma (fu), intrinsic metabolic clearance (CLint), fraction absorbed passively (fa,passive) and maximum fraction dissolved (fdiss) for a variety of compounds in man and investigate the consistency between prediction intervals and observed/measured values.MethodologyCP models featured in the ANDROMEDA software by Prosilico were used for prediction of 70 % confidence intervals of Vss, fu, CLint, fa,passiveand fdissfor compounds from different chemical classes and with broad physicochemical variety and for small drugs marketed in 2021.Results70 % prediction confidence intervals for 217, 117, 117, 89 and 89 compounds were produced for Vss, fu, CLint, fa,passiveand fdiss, respectively. 78 % (expected 70 %) of observed data were within 70 % confidence intervals for the parameters. 70 % of predictions of Vss, fu, CLintfa,passiveand fdissare expected to have errors of maximally 2-, 4- and 6-fold and 7 and 12 %, respectively, which is in line with prediction errors. These findings validate the CP methodology.ConclusionIn conclusion, the results further validate CP models and confidence intervals of ANDROMEDA for prediction of human PK.
Degree-day-based model to predict egg hatching ofPhilaenus spumarius(Hemiptera: Aphrophoridae), the main vector ofXylella fastidiosain Europe
Authors: Lago Clara , Gimenez-Romero Alex , Morente Marina , Matías Manuel A. , Moreno Aránzazu , Fereres Alberto 
Published: November 2022

ABSTRACTPhilaenus spumariusL., the main vector ofXylella fastidiosa(Wells) in Europe, is a univoltine species that overwinters in the egg stage, and its nymphs emerge in late winter or spring. Predicting the time of egg hatching is essential for determining the precise times for deploying control strategies against insect pests. Here, we monitoredP. spumariuseggs from oviposition to egg hatching together with the daily temperatures and relative humidities at four field locations that were located at different altitudes in central Spain. The collected data were used to build a growing degree day (GDD) model to forecast egg hatching in the Iberian Peninsula. Furthermore, the model was validated with field observations that were conducted in Spain. The model was then used as a decision-support tool to calculate the optimum timing for applying control actions againstP. spumarius. Our results suggest that controlling nymphs at two different dates would target the highest percentages of nymphal populations present in the field. Our model represents a first step for predicting the emergence of nymphs and adopting timely control actions againstP. spumarius. These actions could limit disease spread in areas whereX. fastidiosais present.
Encoding of 2D self-centered plans and world-centered positions in the rat frontal orienting field
Authors: Li Liujunli , Flesch Timo , Ma Ce , Li Jingjie , Chen Yizhou , Chen Hung-Tu , Erlich Jeffrey C. 
Published: November 2022

AbstractThe neural mechanisms of motor planning have been extensively studied in rodents. Preparatory activity in the frontal cortex predicts upcoming choice, but limitations of typical tasks have made it challenging to determine whether the spatial information is in a self-centered direction reference frame or a world-centered position reference frame. Here, we trained rats to make delayed visually-guided orienting movements to six different directions, with four different target positions for each direction, which allowed us to disentangle direction versus position tuning in neural activity. We recorded single unit activity from the rat frontal orienting field (FOF) in the secondary motor cortex, a region involved in planning orienting movements. Population analyses revealed that the FOF encodes two separate 2D maps of space. First, a 2D map of the planned and ongoing movement in a self-centered direction reference frame. Second, a 2D map of the animal’s current position on the port wall in a world-centered reference frame. Thus, preparatory activity in the FOF represents self-centered upcoming movement directions, but FOF neurons multiplex both self- and world-reference frame variables at the level of single neurons. Neural network model comparison supports the view that despite the presence of world-centered representations, the FOF receives the target information as self-centered input and generates self-centered planning signals.
Optopharmacological tools for precise spatiotemporal control of oxytocin signaling in the central nervous system and periphery
Authors: Ahmed Ismail A. , Liu Jing-Jing , Gieniec Krystyna A. , Bair-Marshall Chloe J. , Adewakun Ayomiposi B. , Hetzler Belinda E. , Arp Christopher J. , Khatri Latika , Vanwalleghem Gilles C. , Seidenberg Alec T. , Cowin Pamela , Trauner Dirk , Chao Moses V. , Davis Felicity M. , Tsien Richard W. , Froemke Robert C. 
Published: November 2022

AbstractOxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light. We examined how focal versus global oxytocin application affected oxytocin-driven Ca2+wave propagation in mouse mammary tissue. We also validated the application of caged oxytocin in the hippocampus and auditory cortex with electrophysiological recordingsin vitro, and demonstrated that oxytocin uncaging can accelerate the onset of mouse maternal behaviorin vivo. Together, these results demonstrate that optopharmacological control of caged peptides is a robust tool with spatiotemporal precision for modulating neuropeptide signaling throughout the brain and body.
Anatomy Segmentation in Laparoscopic Surgery: Comparison of Machine Learning and Human Expertise – An Experimental Study
Authors: Kolbinger Fiona R. , Rinner Franziska M. , Jenke Alexander C. , Carstens Matthias , Krell Stefanie , Leger Stefan , Distler Marius , Weitz Jürgen , Speidel Stefanie , Bodenstedt Sebastian 
Published: November 2022

Structured AbstractBackgroundLack of anatomy recognition represents a clinically relevant risk in abdominal surgery. Machine learning (ML) methods can help identify visible patterns and risk structures, however, their practical value remains largely unclear.Materials and MethodsBased on a novel dataset of 13195 laparoscopic images with pixel-wise segmentations of eleven anatomical structures, we developed specialized segmentation models for each structure and combined models for all anatomical structures using two state-of-the-art model architectures (DeepLabv3 and SegFormer), and compared segmentation performance of algorithms to a cohort of 28 physicians, medical students, and medical laypersons using the example of pancreas segmentation.ResultsMean Intersection-over-Union for semantic segmentation of intraabdominal structures ranged from 0.28 to 0.83 and from 0.23 to 0.77 for the DeepLabv3-based structure-specific and combined models, and from 0.31 to 0.85 and from 0.26 to 0.67 for the SegFormer-based structure-specific and combined models, respectively. Both the structure-specific and the combined DeepLabv3-based models are capable of near-real-time operation, while the SegFormer-based models are not. All four models outperformed at least 26 out of 28 human participants in pancreas segmentation.ConclusionsThese results demonstrate that ML methods have the potential to provide relevant assistance in anatomy recognition in minimally-invasive surgery in near-real-time. Future research should investigate the educational value and subsequent clinical impact of respective assistance systems.HighlightsMachine learning models to reduce surgical risks that precisely identify 11 anatomical structures: abdominal wall, colon, intestinal vessels (inferior mesenteric artery and inferior mesenteric vein with their subsidiary vessels), liver, pancreas, small intestine, spleen, stomach, ureter and vesicular glandsLarge training dataset of 13195 real-world laparoscopic images with high-quality anatomy annotationsSimilar performance of individual segmentation models for each structure and combined segmentation models in identifying intraabdominal structures, and similar segmentation performance of DeepLabv3-based and SegFormer-based modelsDeepLabv3-based models are capable of near-real-time operation while SegFormer-based models are not, but SegFormer-based models outperform DeepLabv3-based models in terms of accuracy and generalizabilityAll models outperformed at least 26 out of 28 human participants in pancreas segmentation, demonstrating their potential for real-time assistance in recognizing anatomical landmarks during minimally-invasive surgery.
Serial dependence in timing at the perceptual level being modulated by working memory
Authors: Chen Shuai , Wang Tianhe , Bao Yan 
Published: November 2022

AbstractRecent experiences bias the perception of following stimuli, as has been verified in various kinds of experiments in visual perception. This phenomenon, known as serial dependence, may reflect mechanisms to maintain perceptual stability. In the current study, we examined several key properties of serial dependence in temporal perception. Firstly, we examined the source of serial dependence effect in temporal perception. We found that perception without motor reproduction is sufficient to induce the sequential effect; the motor reproduction caused a stronger effect and it is achieved by biasing the perception of the future target duration rather than directly influences the subsequent movement. Secondly, we ask how the working memory influences serial dependence in the in a temporal reproduction task. By varying the delay time between standard duration and the reproduction, we showed that the strength of serial dependence enhanced as the delay increased. Those features of serial dependence are consistent with what has been observed in the visual perceptual tasks, for example, orientation perception or location perception. The similarities between the visual and the timing tasks may suggest a similar neural coding mechanism of magnitude between the visual stimuli and the duration.
Neuromodulatory organization in the developing rat somatosensory cortex
Authors: Colangelo Cristina , Muñoz Alberto , Antonietti Alberto , Antón-Fernández Alejandro , Romani Armando , Herttuainen Joni , Markram Henry , DeFelipe Javier , Ramaswamy Srikanth 
Published: November 2022

AbstractThe vast majority of cortical synapses are found in the neuropil which is implicated in multiple and diverse functions underlying brain computation. Unraveling the organizing principles of the cortical neuropil requires an intricate characterization of synaptic connections established by excitatory and inhibitory axon terminals, of intrinsic and extrinsic origin and from ascending projections that govern the function of cortical microcircuits through the release of neuromodulators either through point-to-point chemical synapses or diffuse volume transmission (VT). Even though neuromodulatory release has been studied for almost a century it is still not clear if one modality prevails upon the other. The hindlimb representation of the somatosensory cortex (HLS1) of two-week old Wistar rats has served as a model system to dissect the microcircuitry of neurons and their synaptic connections. In the present study, we quantified the fiber length per cortical volume and the density of varicosities for cholinergic, catecholaminergic and serotonergic neuromodulatory systems in the cortical neuropil using immunocytochemical staining and stereological techniques. Acquired data were integrated into a novel computational framework to reconcile the specific modalities and predict the effects of neuromodulatory release in shaping neocortical network activity. We predict that acetylcholine (ACh), dopamine (DA), serotonin (5-HT) release desynchronizes cortical activity by inhibiting slow oscillations (delta range), and that 5-HT triggers faster oscillations (theta). Moreover, we found that high levels (>40%) of neuromodulatory VT are sufficient to induce network desynchronization, but also that combining volume release with synaptic inputs leads to more robust and stable effects, meaning that lower levels of VT are needed to achieve the same outcome (10%).
Role of multiple pericentromeric repeats on heterochromatin assembly
Authors: Ghimire Puranjan , Motamedi Mo , Joh Richard I 
Published: November 2022

AbstractAlthough the length and constituting sequences for pericentromeric repeats are highly variable across eukaryotes, the presence of multiple pericentromeric repeats is one of the conserved features of the eukaryotic chromosomes. Pericentromeric heterochromatin is often misregulated in human diseases, with the expansion of pericentromeric repeats in human solid cancers. In this article, we have developed a mathematical model of the RNAi-dependent methylation of H3K9 in the pericentromeric region of fission yeast. Our model, which takes copy number as an explicit parameter, predicts that the pericentromere is silenced only if there are many copies of repeats. It becomes bistable or desilenced if the copy number of repeats is reduced. This suggests that the copy number of pericentromeric repeats alone can determine the fate of heterochromatin silencing in fission yeast. Through sensitivity analysis, we identified parameters that favor bistability and desilencing. Stochastic simulation shows that faster cell division and noise favor the desilenced state. These results show the unexpected role of pericentromeric repeat copy number in gene silencing and elucidate how the copy number of silenced genomic regions may impact genome stability.Author SummaryPericentromeric repeats vary in length and sequences, but their presence is a conserved feature of eukaryotes. This suggests that the repetitive nature of pericentromeric sequences is an evolutionarily conserved feature of centromeres, which is under selective pressure. Here we developed a quantitative model for gene silencing at the fission yeast pericentromeric repeats. Our model is one of the first models which incorporates the copy number of pericentromeric repeats and predicts that the number of repeats can solely govern the dynamics of pericentromeric gene silencing. Our results suggest that the repeat copy number is a dynamic parameter for gene silencing, and copy-number-dependent silencing is an effective machinery to repress the repetitive part of the genome.
Fluoxetine degrades luminance perceptual thresholds while enhancing motivation and reward sensitivity
Authors: Gacoin Maëva , Hamed Suliann Ben 
Published: November 2022

AbstractSelective serotonin reuptake inhibitors (SSRIs) increase serotonin activity in the brain. While they are mostly known for their antidepressant properties, they have been shown to improve visual functions in amblyopia and impact cognitive functions ranging from attention to motivation and sensitivity to reward. Yet, a clear understanding of the specific action of serotonin to each of bottom-up sensory and top-down cognitive control components and their interaction is still missing. To address this question, we characterize, in two adult macaques, the behavioral effects of fluoxetine, a specific SSRI, on visual perception under varying bottom-up (luminosity, distractors) and top-down (uncertainty, reward biases) constraints while they are performing three different visual tasks. We first manipulate target luminosity in a visual detection task, and we show that fluoxetine degrades luminance perceptual thresholds. We then use a target detection task in the presence of spatial distractors, and we show that under fluoxetine, monkeys display both more liberal responses as well as a degraded perceptual spatial resolution. In a last target selection task, involving free choice in the presence of reward biases, we show that monkeys display an increased sensitivity to reward outcome under fluoxetine. In addition, we report that monkeys produce, under fluoxetine, more trials and less aborts, increased pupil size, shorter blink durations, as well as task-dependent changes in reaction times. Overall, while low level vision appears to be degraded by fluoxetine, performance in the visual tasks are maintained under fluoxetine due to enhanced top-down control based on task outcome and reward maximization.
Two motor neuron synergies, invariant across ankle joint angles, activate the triceps surae during plantarflexion
Authors: Levine Jackson , Avrillon Simon , Farina Dario , Hug François , Pons José L. 
Published: November 2022

AbstractRecent studies have suggested that the nervous system generates movements by controlling groups of motor neurons (synergies) that do not always align with muscle anatomy. In this study, we determined whether these synergies are robust across tasks with different mechanical constraints. We identified motor neuron synergies using principal component analysis (PCA) and cross-correlations between smoothed discharge rates of motor neurons. In Part 1, we used simulations to validate these methods. The results suggested that PCA can accurately identify the number of common inputs and their distribution across active motor neurons. Moreover, the results confirmed that cross-correlation can separate pairs of motor neurons that receive common inputs from those that do not receive common inputs. In Part 2, sixteen individuals performed plantarflexion at three ankle angles while we recorded electromyographic signals from the gastrocnemius lateralis (GL) and medialis (GM) and the soleus (SOL) with grids of surface electrodes. PCA revealed two motor neuron synergies. These motor neuron synergies were relatively stable with no significant differences in the distribution of motor neuron weights across ankle angles (p=0.62). When the cross-correlation was calculated for pairs of motor units tracked across ankle angles, we observed that only 13.0% of pairs of motor units from GL and GM exhibited significant correlations of their smoothed discharge rates across angles, confirming the low level of common inputs between these muscles. Overall, these results highlight the modularity of movement control at the motor neuron level, suggesting a sensible reduction of computational resources for movement control.Key points summaryThe central nervous system may generate movements by activating groups of motor neurons (synergies) with common inputs.We show here that two main sources of common inputs drive the motor neurons innervating the triceps surae muscles during isometric ankle plantarflexions.We report that the distribution of these common inputs is globally invariant despite changing the mechanical constraints of the tasks, i.e., the ankle angle.These results suggest the functional relevance of the modular organization of the central nervous system to control movements.
The study of research barriers from the viewpoint of students and faculty members of the faculty of medicine of Azad University of Najaf Abad
Authors: Dormiani Tabatabaei Seyed Amirhossein 
Published: November 2022

AbstractBackgroundUniversities are the most important place for science production and the organization of academic research is one of the most important strategies for community development. The purpose of this study was to identify the barriers of intra-university research in terms of faculty members and students of the faculty of medicine of Islamic Azad University, Najaf Abad.Methods & MaterialsThis cross-sectional study was carried out in the academic year of 2017-2018 and using a researcher-made questionnaire which included 26 questions in the research barriers section. The questions were divided into five areas: the inability of students to implement the research plan, the importance of not considering the system, the lack of access to facilities and facilities, the lack of cooperation of research centers and the lack of access to research and statistical consultants. Validity of the questionnaire was evaluated by experts and authorities, and reliability was calculated by Cronbach’s alpha of 92.8%. The questionnaire was completed by 49 faculty members and 291 students from the faculty of medicine of Islamic Azad University, Najaf Abad. ANOVA, t-test and Spearman test were used to analyze the data.ResultsIn this study, the average grades of students in all areas except the lack of access to facilities and facilities more faculty members. The results of this study showed that there is a significant relationship between the two groups’ views on research barriers in all areas except for the lack of cooperation between research centers (P = 0.395).ConclusionBased on the results of this study, from the viewpoint of faculty and students, research activities are affected by several barriers. The empowerment of human resources, the creation of facilities and facilities, the design of the information and communication system can also be effective in solving the problems and barriers of research.