bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating
Authors: Guan Kaiyun , Lew Daniel J. , Elston Timothy C. 
Published: May 2023

AbstractMany cells adjust the direction of polarized growth or migration in response to external directional cues. The yeastSaccharomyces cerevisiaeorient their cell fronts (also called polarity sites) up pheromone gradients in the course of mating. However, the initial polarity site is often not oriented towards the eventual mating partner, and cells relocate the polarity site in an indecisive manner before developing a stable orientation. During this reorientation phase, the polarity site displays erratic assembly-disassembly behavior and moves around the cell cortex. The mechanisms underlying this dynamic behavior remain poorly understood. Particle-based simulations of the core polarity circuit revealed that molecular-level fluctuations are insufficient to overcome the strong positive feedback required for polarization and generate relocating polarity sites. Surprisingly, inclusion of a second pathway that promotes polarity site orientation generated a mobile polarity site with properties similar to those observed experimentally. This pathway forms a second positive feedback loop involving the recruitment of receptors to the cell membrane and couples polarity establishment to gradient sensing. This second positive feedback loop also allows cells to stabilize their polarity site once the site is aligned with the pheromone gradient.Author summaryCells perform many complex tasks, including directed growth, migration, division and differentiation. To accomplish these tasks, the relevant molecular machinery is localized to specific cellular regions. The asymmetric distribution of cellular components is referred to as cell polarity. Polarity is established by localized activation of the protein Cdc42. Establishing mechanisms that regulate the spatiotemporal activity of Cdc42 is a fundamental area of cell biology. Mating yeast cells dynamically relocate a region of high Cdc42 activity, referred to as the polarity site, and grow toward each other after proper alignment of the sites. We investigated mechanisms that generate dynamic polarity sites by performing particle-based simulations of the biochemical reactions that regulate Cdc42 activity. The reactions contain two positive feedback loops that reinforce Cdc42 activity. The first involves autocatalytic activation of Cdc42 through recruitment of an activator. While necessary for polarity establishment, this feedback loop on its own created a stable polarity site that did not relocate. Incorporation of the second feedback loop, which couples the polarity machinery to extracellular mating signals, generated mobile polarity sites. This feedback loop also provides a mechanism for developing stable alignment of polarity sites. Our findings provide insight into how cells regulate polarity dynamics to accomplish complex tasks.
Upregulation of steroidogenesis is associated with coma in human cerebral malaria
Authors: Abdrabou Wael , Gupta Himanshu , Sahu Praveen K. , Mohanty Akshaya K. , Pattnaik Rajyabardhan , Hoffmann Angelika , Mohanty Sanjib , Wassmer Samuel C. , Idaghdour Youssef 
Published: May 2023

ABSTRACTP. falciparumparasites manipulate host metabolic processes during malaria to ensure their survival and progression, causing the host and parasite metabolic pathways to become intertwined. We analyzed metabolites to evaluate their potential as biomarkers for cerebral malaria (CM). Our analysis of CM (with coma) and CM-like (without coma) patients identified 835 metabolites, including lipids, amino acids, xenobiotics, peptides, nucleotides, carbohydrates, cofactors, and vitamins. Principal component analysis revealed clear segregation between CM-like and CM patients. Metabolite-by-metabolite analysis identified 103 differentially abundant metabolites, 26 of which were significantly lower in CM-like patients (primarily lipids), while 71% of those higher in CM patients were amino acids and xenobiotics. The results revealed significant differences in circulating levels of long chain free fatty acids and catecholamine metabolism and identified steroid biosynthesis as the most enriched lipid metabolism pathway, with eight endogenous steroids showing significantly higher levels in CM patients compared to CM-like patients (FC > 2, B-H FDR-adjusted P < 0.05). These steroids include pregnenolone sulfate, pregnenediol sulfate, pregnenetriol sulfate, androsterone monosulfate, 16α-OH-DHEA-S, DHEA-S, cortisol, and cortisone. High levels of pregnenolone and its downstream metabolic derivatives were significantly associated with coma in CM patients. Our findings suggest that monitoring circulating neurosteroid levels in patients could aid in the early identification of those at risk of coma, and may important implications for the clinical management of CM patients.
Lupus autoantibodies initiate a maladaptive equilibrium sustained by HMGB1:RAGE signaling and reversed by LAIR-1:C1q signaling
Authors: Carroll Kaitlin R. , Mizrachi Mark , Simmons Sean , Toz Bahtiyar , Wingard Jeffrey , Tehrani Nazila , Zarfeshani Aida , Kello Nina , Kowal Czeslawa , Levin Joshua Z. , Volpe Bruce T. , Diamond Betty 
Published: May 2023

AbstractCognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), present in up to 80% of patients and leading to a diminished quality of life. We have developed a model of lupus-like cognitive impairment which is initiated when anti-DNA, anti-N-methyl D-aspartate receptor (NMDAR) cross-reactive antibodies, which are present in 30% of SLE patients, penetrate the hippocampus. This leads to immediate, self-limited excitotoxic death of CA1 pyramidal neurons followed by a significant loss of dendritic arborization in the remaining CA1 neurons and impaired spatial memory. Both microglia and C1q are required for dendritic loss. Here we show that this pattern of hippocampal injury creates a maladaptive equilibrium that is sustained for at least one year. It requires HMGB1 secretion by neurons to bind RAGE, a receptor for HMGB1 expressed on microglia, and leads to decreased expression of microglial LAIR-1, an inhibitory receptor for C1q. The angiotensin converting enzyme (ACE) inhibitor captopril, which can restore a healthy equilibrium, microglial quiescence, and intact spatial memory, leads to upregulation of LAIR-1. This paradigm highlights HMGB1:RAGE and C1q:LAIR-1 interactions as pivotal pathways in the microglial–neuronal interplay that defines a physiologic versus a maladaptive equilibrium.
Modelling complex growth profiles ofBacteroides fragilisandEscherichia colion various carbohydrates in an anaerobic environment
Authors: McGuire Zachary , Revuru Sainitya , Zhang Sheng , Blankenberger Amanda , Rasheed Moiz , Hosen Jacob D. , Lin Guang , Verma Mohit S. 
Published: May 2023

AbstractPreviously published models for microbial growth focus only on either death or growth and are unable to account for differently shaped growth curves. Currently, there is no model capable of incorporating combinations of microbial growth trends. This study creates a bacterial growth model that incorporates growth, death, lag, and tail phases as well as applies this model to the growth trends ofBacteroides fragilisandEscherichia colion 13 different carbohydrate substances. Growth trends were collected by measuring the optical densities over 72 hours for eitherB. fragilisorE. coliin a chemically defined media supplemented by a mono- or disaccharide. The Digital Environment to Enable Data-driven Science (DEEDS) platform was utilized to parse data and apply the developed model to obtain parameter values.E. coliwas found to grow on the chemically defined media alone whileB. fragiliswas unable to grow on it alone.E. coligrowth was led by 10 mM concentration of substrates whileB. fragilis growthwas substrate dependent. Bacterial death only occurred forB. fragilisbut was found to be dependent on concentration for the two most significant substrates. A singular model was developed that does not require prior knowledge of metabolomics and is capable of incorporating a combination of growth and death trends.
Rapid effects of valproic acid on the fetal brain transcriptome: Implications for brain development and autism
Authors: Dorsey Susan G. , Mocci Evelina , Lane Malcolm V. , Krueger Bruce K. 
Published: May 2023

ABSTRACTThere is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPAin uterocauses autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration revealed that VPA significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders (NDDs) such as autism as well as neurogenesis, axon growth and synaptogenesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 399 autism risk genes was significantly altered by VPA as was expression of 252 genes that have been reported to play fundamental roles in the development of the nervous system but are not otherwise linked to autism. The goal of this study was to identify mouse genes that are:(a) significantly up- or down-regulated by VPA in the fetal brainand(b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain.The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in NDDs such as autism.
Variance Analysis of LC-MS Experimental Factors and Their Impact on Machine Learning
Authors: Rehfeldt Tobias Greisager , Krawczyk Konrad , Echers Simon Gregersen , Marcatili Paolo , Palczynski Pawel , Röttger Richard , Schwämmle Veit 
Published: May 2023

AbstractBackgroundMachine learning (ML) technologies, especially deep learning (DL), have gained increasing attention in predictive mass spectrometry (MS) for enhancing the data processing pipeline from raw data analysis to end-user predictions and re-scoring. ML models need large-scale datasets for training and re-purposing, which can be obtained from a range of public data repositories. However, applying ML to public MS datasets on larger scales is challenging, as they vary widely in terms of data acquisition methods, biological systems, and experimental designs.ResultsWe aim to facilitate ML efforts in MS data by conducting a systematic analysis of the potential sources of variance in public MS repositories. We also examine how these factors affect ML performance and perform a comprehensive transfer learning to evaluate the benefits of current best practice methods in the field for transfer learning.ConclusionsOur findings show significantly higher levels of homogeneity within a project than between projects, which indicates that it’s important to construct datasets most closely resembling future test cases, as transferability is severely limited for unseen datasets. We also found that transfer learning, although it did increase model performance, did not increase model performance compared to a non-pre-trained model.
Discrete cortical control during quiet stance revealed by desynchronization and rebound of beta oscillations
Authors: Nakamura Akihiro , Miura Ryota , Suzuki Yasuyuki , Morasso Pietro , Nomura Taishin 
Published: May 2023

AbstractPostural sway during quiet stance often exhibits a repetition of micro fall and the subsequent micro recovery. The classical view –that the quiet bipedal stance is stabilized by the ankle joint stiffness– has been challenged by paradoxical non-spring-like behaviors of calf muscles: gastrocnemius muscles are shortened (contract) and then stretched (relax), respectively, during the micro fall and the micro recovery. Here, we examined EEG (electroencephalogram) based brain activity during quiet stance, and identified desynchronization and synchronization of beta oscillations that were associated, respectively, with the micro fall and the micro recovery. Based on a widely accepted scenario for beta-band desynchronization during movement and post-movement rebound in the control of discrete voluntary movement, our results reveal that the beta rebound can be considered as a manifestation of stop command to punctuate the motor control for every fall-recovery cycle. Namely, cortical interventions to the automatic postural control are discrete, rather than continuous modulations. The finding is highly compatible with the intermittent control model, rather than the stiffness control model.
Renal tubular function and morphology revealed in kidney without labeling using three-dimensional dynamic optical coherence tomography
Authors: Mukherjee Pradipta , Fukuda Shinichi , Lukmanto Donny , Tran Thi Hang , Okada Kosuke , Makita Shuichi , El-Sadek Ibrahim Abd , Lim Yiheng , Yasuno Yoshiaki 
Published: May 2023

ABSTRACTRenal tubule has distinct metabolic features and functional activity that may be altered during kidney disease. In this paper, we present label-free functional activity imaging of renal tubule in normal and obstructed mouse kidney models using three-dimensional (3D) dynamic optical coherence tomography (OCT)ex vivo. To create an obstructed kidney model, we ligated the ureter of the left kidney for either 7 or 14 days. Two different dynamic OCT (DOCT) methods were implemented to access the slow and fast activity of the renal tubules: a logarithmic intensity variance (LIV) method and a complex-correlation-based method. Three-dimensional DOCT data were acquired with a 1.3 μm swept-source OCT system and repeating raster scan protocols. In the normal kidney, the renal tubule appeared as a convoluted pipe-like structure in the DOCT projection image. Such pipe-like structures were not observed in the kidneys subjected to obstruction of the ureter for several days. Instead of any anatomical structures, a superficial high dynamics appearance was observed in the perirenal cortex region of the obstructed kidneys. These findings suggest that volumetric DOCT can be used as a tool to investigate kidney function during kidney diseases.
Collagen of ancient bones gives an indication of endogenous DNA preservation based on the next generation sequencing technology
Authors: Nakamura Yuka , Waku Daisuke , Wakiyama Yoshiki , Watanabe Yusuke , Koganebuchi Kae , Nagaoka Tomohito , Hirata Kazuaki , Ohashi Jun , Takahashi Ryuzaburo , Yoneda Minoru , Oota Hiroki 
Published: May 2023

AbstractAncient genome analysis has become an indispensable tool in studies of human population history and evolution after the breakthrough of whole genome sequencing technology. Meanwhile, the problem has been not resolved that ancient genome cannot be analyzed without crushing non-small pieces of precious specimens; in spite of that, in many cases, there is no DNA remaining sufficiently in the piece of samples for obtaining the whole genome sequences. In previous studies, therefore, a couple of indicators (e.g., racemization ratios) have been proposed to estimate the endogenous DNA in ancient samples. However, these studies have used polymerase chain reaction (PCR) to test whether endogenous DNA is remaining, which has been inadequate because the success or failure of PCR amplification does not necessarily reflect DNA remaining. To assess the amount of endogenous DNA, we use the ratios of reads generated by the next-generation sequencer (NGS) mapped to the human reference genome sequence. We investigate 40 Jomon remains and find a significant association between the collagen residual ratios (CRRs) in rib bones and the mapping ratios (MRs). Because the weight of bone required to measure collagen residual is much less than that required to obtain DNA needed for NGS analysis, which is always necessary for dating, the collagen in ribs can be a good indicator for successful ancient genome analyses.
Cellular Dynamics of Skeletal Muscle Regeneration
Authors: Collins Brittany C. , Shapiro Jacob B. , Scheib Mya M. , Musci Robert V. , Verma Mayank , Kardon Gabrielle 
Published: May 2023

SUMMARYThe function of many organs, including skeletal muscle, depends on its three-dimensional structure. Muscle regeneration therefore requires not only reestablishment of myofibers, but restoration of tissue architecture. Resident muscle stem cells (SCs) are essential for regeneration, but how SCs regenerate muscle architecture is largely unknown. We address this problem using genetic labeling of SCs and whole mount imaging to reconstruct in three dimensions muscle regeneration. Unexpectedly, we found that the residual basement membrane of necrotic myofibers is critical for promoting fusion and orienting regenerated myofibers and myofibers form via two distinct phases of fusion. Furthermore, the centralized myonuclei characteristic of regenerated myofibers are associated with myofibrillogenesis and permanently mark regenerated myofibers. Finally, we elucidate a new cellular mechanism for the formation of branched myofibers, a pathology characteristic of diseased muscle. We provide a new synthesis of the cellular events of regeneration and show these differ from those used during development.
A Narrow Range of Transcript-error Rates Across the Tree of Life
Authors: Li Weiyi , Baehr Stephan , Marasco Michelle , Reyes Lauren , Brister Danielle , Pikaard Craig S. , Gout Jean-Francois , Vermulst Marc , Lynch Michael 
Published: May 2023

AbstractThe expression of genomically-encoded information is not error-free. Transcript-error rates are dramatically higher than DNA-level mutation rates, and despite their transient nature, the steady-state load of such errors must impose some burden on cellular performance. However, a broad perspective on the degree to which transcript-error rates are constrained by natural selection and diverge among lineages remains to be developed. Here, we present a genome-wide analysis of transcript-error rates across the Tree of Life using a modified rolling-circle sequencing method, revealing that the range in error rates is remarkably narrow across diverse species. Transcript errors tend to be randomly distributed, with little evidence supporting local control of error rates associated with gene-expression levels. A majority of transcript errors result in missense errors if translated, and as with a fraction of nonsense transcript errors, these are underrepresented relative to random expectations, suggesting the existence of mechanisms for purging some such errors. To quantitatively understand how natural selection and random genetic drift might shape transcript-error rates across species, we present a model based on cell biology and population genetics, incorporating information on cell volume, proteome size, average degree of exposure of individual errors, and effective population size. However, while this model provides a framework for understanding the evolution of this highly conserved trait, as currently structured it explains only 20% of the variation in the data, suggesting a need for further theoretical work in this area.
An E-I Firing Rate Model for Gamma Oscillations
Authors: Lu Yiqing , Rinzel John 
Published: May 2023

AbstractFiring rate models for describing the mean-field activities of neuronal ensembles can be used effectively to study network function and dynamics, including synchronization and rhythmicity of excitatory-inhibitory populations. However, traditional Wilson-Cowan-like models, being amenable to mathematical analysis, are found unable to capture some dynamics such as Interneuronal Network Gamma oscillations (ING) although use of an explicit delay can help. We resolve this issue by introducing a mean-voltage variable (v) that considers the subthreshold integration of inputs and works as an effective delay in the negative feedback loop between firing rate (r) and synaptic gating of inhibition (s). Here we describe a three-variabler-s-vfiring rate model for I-I networks, which is biophysically interpretable and capable of generating ING-like oscillations. Linear stability analysis, numerical branch-tracking and simulations show that the rate model captures many of the common features of spiking network models for ING. We also propose an alternativer-u-smodel for ING which considers an implicit delay by a pre-synaptic variableu. Furthermore, we extend the framework to E-I networks. With our six-variabler-s-vmodel, we describe for the first time in firing rate models the transition from Pyramidal-Interneuronal Network Gamma (PING) to ING by increasing the external drive to the inhibitory population without adjusting synaptic weights. Having PING and ING available in a single network, without invoking synaptic blockers, is plausible and natural for explaining the emergence and transition of two different types of gamma oscillations.Author SummaryGamma rhythm (30-90 Hz) is a neuronal oscillation broadly observed across various animal species. It is associated with cognitive functions and gamma oscillation dysfunction has been found in neurological diseases. Traditional studies of gamma oscillations are primarily conducted in detailed but computational demanding spiking network models. Motivated by the growing size of accessible datasets and large-scale modeling, we develop mean-field representations of gamma oscillations that are computationally lightweight and mathematically analyzable. We resolve the incapability of generating oscillation in inhibitory network with traditional Wilson-Cowan firing rate model by introducing implicit delay with a mean membrane potential variable and generalize the model for excitatory-inhibitory network to capture richer dynamics. Our work provides a potential building block for multi-area large-scale modeling to help understanding the functional roles of circuits at different levels.