bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Open-Source Rodent Chronic EEG Array System with High Density MXene-Based Skull Surface Electrodes
Authors: Ding Li , Patel Aashvi , Shankar Sneha , Driscoll Nicolette , Zhou Chengwen , Rex Tonia S , Vitale Flavia , Gallagher Martin J. 
Published: December 2022

AbstractElectroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring a major surgery, this intracranial EEG technique is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two channel (EEG2) and sixteen channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti3C2Tx) MXene. The MXene electrodes are placed on the surface of the intact skull and establish electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach and recorded resting baseline and epileptiform EEG waveforms are similar to those obtained with traditional epidural electrodes. Applying HdEEG to a mild traumatic brain injury (mTBI) model in mice of both sexes revealed that mTBI significantly altered awake resting state spectral density with a spatiospectral region of interest in the β spectral band (12-30 Hz) in the central and posterior regions. These findings indicate that fabrication of MXene electrode arrays is a cost effective, efficient technology for multichannel EEG recording in rodents that obviates the need for skull-penetrating surgery. Moreover, increased β spectral power may contribute to the development of early post-mTBI seizures.Significance StatementElectroencephalography (EEG) is a critical technique used to study neurological activity in rodents. Commonly used EEG procedures require time-consuming skull-penetrating surgeries that may confound the experiments. Here we provide a cost-effective solution for obtaining two channel (EEG2) and high-density EEG (HdEEG) recordings on the skull surface thus avoiding major surgery. We compared this HdEEG system to traditional EEG recordings and then used it to determine the effects of mild traumatic brain injury on awake resting state spectral density. This novel open-source EEG system will contribute the electrophysiological characterization of rodent behaviors and seizure activity.
Neuronal TIMP2 regulates hippocampus-dependent plasticity and extracellular matrix complexity
Authors: Ferreira Ana Catarina , Hemmer Brittany M. , Philippi Sarah M. , Liu Hanxiao , Zhu Jeffrey D. , Kareva Tatyana , Ahfeldt Tim , Varghese Merina , Hof Patrick R. , Castellano Joseph M. 
Published: December 2022

AbstractThe functional output of the hippocampus, a brain region subserving memory processes, depends on highly orchestrated cellular and molecular processes that regulate synaptic plasticity throughout life. The structural requirements of such plasticity and molecular processes involved in this regulation are poorly understood. Specific molecules, including tissue inhibitor of metalloproteinases-2 (TIMP2) have been implicated in processes of plasticity in the hippocampus, a role that decreases with brain aging as expression is lost. Here, we report that TIMP2 is highly expressed by neurons within the hippocampus and its loss drives changes in cellular programs related to adult neurogenesis and dendritic spine turnover with corresponding impairments in hippocampus-dependent memory. Consistent with the accumulation of ECM in the hippocampus we observe with aging, we find that TIMP2 acts to reduce accumulation of extracellular matrix (ECM) around synapses in the hippocampus. Moreover, its removal results in hindrance of newborn neuron migration through a denser ECM network. A novel conditional TIMP2 KO mouse reveals that neuronal TIMP2 regulates adult neurogenesis, accumulation of ECM, and ultimately hippocampus-dependent memory. Our results define a mechanism whereby hippocampus- dependent function is regulated by TIMP2 and its interactions with the ECM to regulate diverse processes associated with synaptic plasticity.
The cost of multiplexing: PFC integrates multiple sources of information in non-orthogonal components accounting for behavioral variability
Authors: Amengual Julian L , Bello Fabio Di , Hassen Sameh Ben Hadj , Gaillard Corentin , Astrand Elaine , Hamed Suliann Ben 
Published: December 2022

AbstractThe frontal eye field (FEF) is a cortical area classically associated with spatial attention, perception, and oculomotor functions. FEF exhibits complex response properties through mixed selectivity neurons, allowing a high dimensional representation of the information. However, recent studies have shown that FEF encodes information in a low-dimensional regime hence limiting the coding capacity of the neural population. How the FEF encodes multiple sources of information with such limited encoding capacity remains elusive. To address this question, we trained two macaques to perform a visual attention task while we recorded FEF neuronal activity using multi-contact electrodes. FEF neurons encoded task- (time in the trial; CTOA) and behaviour- (reaction time, RT; focus of attention, TA) related parameters prior to the target onset. We found a clear modulation of the RT and TA as a function of the CTOA. Using dPCA, we characterized the functional relationship between neural populations associated with each parameter and investigated how this functional relationship predicts behaviour. We found that CTOA variability was associated with two different components the activation of which was correlated with the TA and the RT, respectively. These CTOA-related components were non-orthogonal with the RT and TA-related components, respectively. These results suggest that, when different sources of information are implemented during task performance, they show a very precise geometrical configuration in non-orthogonal components, which allows a high capacity of information coding at a cost of modulating both the capacity of the monkey to use attention information and its responsiveness toward external stimuli.
Injectable MSC Spheroid and Microgel Granular Composites for Engineering Cartilage Tissue
Authors: Di Caprio Nikolas , Davidson Matthew D. , Daly Andrew C. , Burdick Jason A. 
Published: December 2022

AbstractArticular cartilage is important for joint function, yet it can be damaged due to disease or trauma. Cartilage lacks natural healing processes and current clinical treatments are limited in their ability to form functional cartilage for repair. Here, we reimagine cartilage tissue engineering with an approach that combines aggregates of adult MSCs (spheroids) with hydrogel microparticles (microgels) to form granular composites that are injectable, permit cell-cell contacts for chondrogenesis, allow spheroid fusion and growth, and undergo interparticle crosslinking post-injection via light for stability. We use simulations and experimental analyses to establish the importance of initial MSC spheroid to microgel volume ratios in granular composites that balance mechanical support with tissue growth. Long-term chondrogenic cultures of granular composites produce engineered cartilage tissue within the range of native properties, which can be further enhanced via MSC/chondrocyte co-cultures. Altogether, we have developed a new strategy of injectable granular composites for engineering cartilage tissue.
Dynamic protein deacetylation is a limited carbon source for acetyl-CoA-dependent metabolism
Authors: Soaita Ioana , Megill Emily , Kantner Daniel , Chatoff Adam , Arany Zoltan , Snyder Nathaniel W , Wellen Kathryn E , Trefely Sophie 
Published: December 2022

AbstractThe ability of cells to store and rapidly mobilize energy reserves in response to nutrient availability is essential for survival. Breakdown of carbon stores produces acetyl-coenzyme-A (acetyl-CoA), which fuels various metabolic pathways and is also the acyl donor for protein lysine acetylation. Notably, histone acetylation is sensitive to acetyl-CoA availability and nutrient replete conditions induce a substantial accumulation of acetylation on histones. Deacetylation releases acetate, which can be recycled to acetyl-CoA, suggesting that deacetylation could be mobilized as an acetyl-CoA source to feed downstream metabolic processes under nutrient depletion. While the notion of histones as a metabolic reservoir has been frequently proposed, experimental evidence has been lacking. Therefore, to test this concept directly, we developed an experimental system to trace deacetylation-derived acetate and its incorporation into acetyl-CoA, using13C2-acetate in ATP citrate lyase-deficient fibroblasts (Acly-/-MEFs), which are primarily dependent on acetate for protein acetylation. We find that dynamic protein deacetylation inAcly-/-MEFs contributes carbons to acetyl-CoA and proximal downstream metabolites. However, there is no significant effect on acyl-CoA pool sizes, and even at maximal acetylation, deacetylation transiently supplies approximately 9% of cellular acetyl-CoA. Together, our data reveal that although protein acetylation is dynamic and sensitive to nutrient availability, its potential for maintaining cellular acetyl-CoA-dependent metabolic pathways is limited compared to cellular demand.
Ultra-Accurate Classification and Discovery of Functional Protein-Coding Genes from Microbiomes Using FunGeneTyper: An Expandable Deep Learning-Based Framework
Authors: Zhang Guoqing , Wang Hui , Zhang Zhiguo , Zhang Lu , Guo Guibing , Yang Jian , Yuan Fajie , Ju Feng 
Published: December 2022

AbstractHigh-throughput DNA sequencing technologies open the gate to tremendous (meta)genomic data from yet-to-be-explored microbial dark matter. However, accurately assigning protein functions to new gene sequences remains challenging. To this end, we developed FunGeneTyper, an expandable deep learning-based framework with models, structured databases and tools for ultra-accurate (>0.99) and fine-grained classification and discovery of antibiotic resistance genes (ARGs) and virulence factor or toxin genes. Specifically, this new framework achieves superior performance in discovering new ARGs from human gut (accuracy: 0.8512; and F1-score: 0.6948), wastewater (0.7273; 0.6072), and soil (0.8269; 0.5445) samples, beating the state-of-the-art bioinformatics tools and protein sequence-based (F1-score: 0.0556-0.5065) and domain-based (F1-score: 0.2630-0.5224) alignment approaches. We empowered the generalized application of the framework by implementing a lightweight, privacy-preserving and plug-and-play neural network module shareable among global developers and users. The FunGeneTyper*is released to promote the monitoring of key functional genes and discovery of precious enzymatic resources from diverse microbiomes.
DI/cle, a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Captures Diabetic States
Authors: Sugimoto Hikaru , Hironaka Ken-ichi , Yamada Tomoko , Sakaguchi Kazuhiko , Ogawa Wataru , Kuroda Shinya 
Published: December 2022

ABSTRACTContextInsulin clearance is implicated in regulation of glucose homeostasis independently of insulin sensitivity and insulin secretion.ObjectiveTo understand the relation between blood glucose and insulin sensitivity, secretion, and clearance.MethodsWe performed a hyperglycemic clamp, a hyperinsulinemic-euglycemic clamp, and an oral glucose tolerance test (OGTT) in 47, 16, and 49 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. Mathematical analyses were retrospectively performed on this dataset.ResultsThe disposition index (DI), defined as the product of insulin sensitivity and secretion, showed a weak correlation with blood glucose levels, especially in IGT (r= 0.04; 95% CI, −0.63– 0.44). However, an equation relating DI, insulin clearance, and blood glucose levels was well conserved regardless of the extent of glucose intolerance. As a measure of the effect of insulin, we developed an index, designated “DI/cle,” that is based on this equation and corresponds to DI divided by the square of insulin clearance. DI/cle was not impaired in IGT compared with NGT, possibly as a result of a decrease in insulin clearance in response to a reduction in DI, whereas it was impaired in T2DM relative to IGT. Moreover, DI/cle estimated from a hyperinsulinemic-euglycemic clamp, OGTT, or a fasting blood test were significantly correlated with that estimated from two clamp tests (r= 0.52; 95% CI, 0.37– 0.64,r= 0.43; 95% CI, 0.24– 0.58, andr= 0.54; 95% CI, 0.38– 0.68, respectively).ConclusionsDI/cle can serve as a new indicator for the trajectory of changes in glucose tolerance.
The Warburg Effect is the result of faster ATP production by glycolysis than respiration
Authors: Kukurugya Matthew A. , Titov Denis V. 
Published: December 2022

AbstractMany prokaryotic and eukaryotic cells metabolize glucose to organism-specific byproducts instead of fully oxidizing it to carbon dioxide and water–a phenomenon referred to as the Warburg Effect. The benefit to a cell has been unclear, given that partial metabolism of glucose yields an order of magnitude less ATP per molecule of glucose than complete oxidation. We show that glycolysis produces ATP faster per gram of pathway protein than respiration inE. coli,S. cerevisiae, and mammalian cells. A simple mathematical model that uses yield, rate, and proteome occupancy of glycolysis and respiration as the only parameters accurately predicts absolute rates of glycolysis and respiration in all three organisms under diverse conditions. Our study suggests that the Warburg Effect is a consequence of the optimization of the rate of energy generation under the constraint of finite proteome space.One-Sentence SummaryThe Warburg Effect is a manifestation by which cells across kingdoms of life optimize the rate of energy production.
Turnover of strain-level diversity modulates functional traits in the honeybee gut microbiome between nurses and foragers
Authors: Baud Gilles LC , Prasad Aiswarya , Ellegaard Kirsten M , Engel Philipp 
Published: December 2022

AbstractStrain-level diversity is widespread among bacterial species and can expand the functional potential of natural microbial communities. However, to what extent communities undergo consistent shifts in strain composition in response to environmental/host changes is less well understood. Here, we used shotgun metagenomics to compare the gut microbiota of two behavioral states of the Western honeybee (Apis mellifera), namely nurse and forager bees. While their gut microbiota is composed of the same bacterial species, we detected consistent changes in strain-level composition between nurses and foragers. Single nucleotide variant profiles of predominant bacterial species clustered by behavioral state. Moreover, we identified strain-specific gene content related to nutrient utilization, vitamin biosynthesis, and cell-cell interactions specifically associated with the two behavioral states. Our findings show that strain-level diversity in host-associated communities can undergo consistent changes in response to host behavioral changes modulating the functional potential of the community.
Social context modulates multibrain broadband dynamics and functional brain-to-brain coupling in the group of mice
Authors: Lee Jeongyoon , Kwak Damhyeon , Lee Gwang Ung , Kim Chan Yeong , Park Sang Hyun , Choi Jee Hyun , Lee Sung Q. , Choe Han Kyoung 
Published: December 2022

AbstractAlthough mice are social animals, studies that explore the simultaneously recorded neural activities of multiple mice, especially in a social setting, are still lacking. In this study, we simultaneously recorded local field potential (LFP) signals in the dorsomedial prefrontal cortex (dmPFC) from up to four mice. The brain activities of the mice were measured in two contradicting conditions - freely interacting in a group or being individually separated. We found that social context and the locomotive states predominately modulate the entire LFP structure. Power spectral density (PSD) estimate and spectrogram of LFP signals showed a broadband modulation; lower frequency bands—delta (<4Hz), theta (4-7Hz), and alpha (8-12Hz) power were highly correlated to each other and anti-correlated with gamma and high gamma (>30Hz) power. We calculated the high-to-low-power ratio (HLR) and found that HLR was higher when the mice were in a group than were separated. The HLR was also higher when they were active—whether or not they were moving. The mice in the group showed higher HLR in any locomotive states. We then analyzed whether social context can be divided into sub-contexts. Notably, the aggregation of animals, called huddling, decreased social context-induced increase in HLR. Multibrain analyses of HLR indicated that the mice in the group displayed high cross-correlation to each other, indicating interbrain synchrony. Then we examined whether there is any directional relationship between HLR from pairs of mice. A majority of dyad selected within the group of mice showed unilateral precedence of HLR by Granger causality analysis, comprising a hierarchical social structure based on a directionality of influence. Overall, this study shows the importance of the social environment in brain dynamics and emphasizes the value of simultaneous multibrain recording for researching social behaviors and their neural correlates.One-sentence summaryCoexistence modulates overall brain activities with unilateral causal relationship.
Chromatin organization drives the exploration strategy of nuclear factors
Authors: Mazzocca Matteo , Loffreda Alessia , Colombo Emanuele , Fillot Tom , Gnani Daniela , Falletta Paola , Monteleone Emanuele , Capozi Serena , Bertrand Edouard , Legube Gaelle , Lavagnino Zeno , Tacchetti Carlo , Mazza Davide 
Published: December 2022

AbstractNuclear Factors (NFs) rapidly scan the genome for their targets, but the role of nuclear organization in such search is uncharted. Here we analyzed how multiple NFs explore chromatin, by combining live-cell single-molecule tracking with multifocal structured illumination of DNA density. We find that NFs displaying higher bound fractions sample DNA dense regions more exhaustively. Focusing on the tumor-suppressor p53, we demonstrated that this NF search for its targets by alternating between rapid diffusion in the interchromatin compartment and compact sampling of chromatin dense regions. Efficient p53 targeting requires balanced IDR/chromatin interactions: adding an exogenous IDR potentiates p53-mediated target gene activation, but excessive IDR/IDR interactions lead to p53 condensates, derailing its search and downregulating transcription. Our findings highlight the role of NF IDRs on their search and showcase a powerful method to generate traffic maps of the eukaryotic nucleus and dissect how nuclear organization guides NFs action.
Longitudinal Characterization of Cerebral Hemodynamics in the TgF344-AD Rat Model of Alzheimer’s Disease
Authors: Fang Xing , Tang Chengyun , Zhang Huawei , Border Jane J. , Liu Yedan , Shin Seung Min , Yu Hongwei , Roman Richard J. , Fan Fan 
Published: December 2022

ABSTRACTAlzheimer’s Disease (AD) is a global healthcare crisis. The TgF344-AD rat is an AD model exhibiting age-dependent AD pathological hallmarks. We confirmed that AD rats developed cognitive deficits at 6 months without alteration of any other major biophysical parameters. We longitudinally characterized cerebral hemodynamics in AD rats at 3, 4, 6, and 14 months. The myogenic responses of the cerebral arteries and arterioles were impaired at 4 months of age in the AD rats. Consistent with theex vivoresults, the AD rat exhibited poor autoregulation of surface and deep cortical cerebral blood flow two months preceding cognitive decline. The dysfunction of cerebral hemodynamics in AD is exacerbated with age associated with reduced cerebral perfusion. Further, abolished cell contractility contributes to cerebral hemodynamics imbalance in AD. This may be attributed to enhanced ROS production, reduced mitochondrial respiration and ATP production, and disrupted actin cytoskeleton in cerebral vascular contractile cells.
Why the brown ghost chirps at night
Authors: Oboti Livio , Pedraja Federico , Ritter Marie , Lohse Marlena , Klette Lennart , Krahe Rüdiger 
Published: December 2022

AbstractSince the pioneering work by Moeller, Szabo, and Bullock, weakly electric fish have served as a valuable model for investigating spatial and social cognitive abilities in a vertebrate taxon usually less accessible than mammals or other terrestrial vertebrates. These fish, through their electric organ, generate low-intensity electric fields to navigate and interact with conspecifics, even in complete darkness. The brown ghost knifefish is appealing as a study subject due to a rich electric “vocabulary”, made by individually variable and sex-specific electric signals. These are mainly characterized by brief frequency modulations of the oscillating dipole moment continuously generated by their electric organ, and are known as chirps. Different types of chirps are believed to convey specific and behaviorally salient information, serving as behavioral readouts for different internal states during behavioral observations. Despite the success of this model in neuroethology over the past seven decades, the code to decipher their electric communication remains unknown.To this aim, in this study we re-evaluate the correlations between signals and behavior offering an alternative, and possibly complementary, explanation for why these freshwater bottom dwellers emit electric chirps. By uncovering correlations among chirping, electric field geometry, and detectability in enriched environments, we present evidence for a previously unexplored role of chirps as specialized self-directed signals, enhancing conspecific electrolocation during social encounters.
The SAGA HAT module is tethered by its SWIRM domain and modulates activity of the SAGA DUB module
Authors: Haile Sara T. , Rahman Sanim , Orsburn Benjamin C. , Bumpus Namandjé N. , Wolberger Cynthia 
Published: December 2022

AbstractThe SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is a transcriptional coactivator that both acetylates and deubiquitinates histones. The histone acetyltransferase (HAT) subunit, Gcn5, is part of a subcomplex of SAGA called the HAT module. A minimal HAT module complex containing Gcn5 bound to Ada2 and Ada3 is required for full Gcn5 activity on nucleosomes. Deletion studies have suggested that the Ada2 SWIRM domain plays a role in tethering the HAT module to the remainder of SAGA. While recent cryo-EM studies have resolved the structure of the core of the SAGA complex, the HAT module subunits and molecular details of its interactions with the SAGA core could not be resolved. Here we show that the SWIRM domain is required for incorporation of the HAT module into the yeast SAGA complex, but not the ADA complex, a distinct six-protein acetyltransferase complex that includes the SAGA HAT module proteins. In the isolated Gcn5/Ada2/Ada3 HAT module, deletion of the SWIRM domain modestly increased activity but had negligible effect on nucleosome binding. Loss of the HAT module due to deletion of the SWIRM domain decreases the H2B deubiquitinating activity of SAGA, indicating a role for the HAT module in regulating SAGA DUB module activity. A model of the HAT module created with Alphafold Multimer provides insights into the structural basis for our biochemical data, as well as prior deletion studies.