bluuebunny/crossref_metadata_2025_split huggingface dataset:
FONDUE: Robust resolution-invariant denoising of MR Images using Nested UNets
Authors: Adame-Gonzalez Walter , Brzezinski-Rittner Aliza , Chakravarty M. Mallar , Farivar Reza , Dadar Mahsa 
Published: June 2023

ABSTRACTRecent human neuroimaging studies tend to have increased magnetic resonance image (MRI) acquisition resolutions, seeking finer levels of detail and more accurate brain morphometry. However, higher-resolution images inherently contain greater amounts of noise contamination, leading to poorer quality brain morphometry if not addressed adequately. This study proposes a novel, robust, resolution-invariant deep learning method to denoise structural human brain MRIs. We explore denoising of T1-weighted (T1w) brain images from varying field strengths (1.5T to 7T), voxel sizes (1.2mm to 250µm), scanner vendors (Siemens, GE, and Phillips), and diseased and healthy participants from a wide age range (young adults to aging individuals). Our proposed Fast-Optimized Network for Denoising through residual Unified Ensembles (FONDUE) method demonstrated stable denoising capabilities across multiple resolutions with performance comparable to the state-of-the-art methods. FONDUE was capable of denoising 0.5mm3isotropic T1w images in under 3 minutes on an NVIDIA RTX 3090 GPU using less than 8GB of video memory. We have also made the repository of FONDUE as well as its trained weights publicly available on:https://github.com/waadgo/FONDUE.
Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures
Authors: Connolly Mark J. , Jiang Sujin , Samuel Lim , Gutekunst Claire-Anne , Gross Robert E. , Devergnas Annaelle 
Published: June 2023

AbstractTemporal lobe (TL) epilepsy is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit and the structures composing the temporal lobe. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Evidence suggests that the network involved in temporal lobe seizure may depend on their onset and offset pattern but studies on the relationship between the patterns and extralimbic activity are limited. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe seizures induced in two nonhuman primates (NHP). The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then analyzed the three first and last seconds of the seizure as well as 3-second segments of recorded in pre-ictal and post-ictal periods and compared the changes based on the seizure onset and offset patterns.Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that seizures with both low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase of HPC/SI coherence was similar for both type of onset, while the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This result suggests that the SN might be involved differently in the termination of the BS seizure pattern. This study constitutes the first demonstration of temporal lobe seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the seizure onset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.
Processing macromolecular diffuse scattering data
Authors: Meisburger Steve P. , Ando Nozomi 
Published: June 2023

AbstractDiffuse scattering is a powerful technique to study disorder and dynamics of macromolecules at atomic resolution. Although diffuse scattering is always present in diffraction images from macromolecular crystals, the signal is weak compared with Bragg peaks and background, making it a challenge to visualize and measure accurately. Recently, this challenge has been addressed using the reciprocal space mapping technique, which leverages ideal properties of modern X-ray detectors to reconstruct the complete three-dimensional volume of continuous diffraction from diffraction images of a crystal (or crystals) in many different orientations. This chapter will review recent progress in reciprocal space mapping with a particular focus on the strategy implemented in themdx-libandmdx2software packages. The chapter concludes with an introductory data processing tutorial using Python packagesDIALS, NeXpy, andmdx2.
Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation
Authors: Bravo-Jaimes Katia , Wu Xiuju , Reardon Leigh C , Lluri Gentian , Lin Jeannette P , Moore Jeremy P , Arsdell Glen Van , Biniwale Reshma , Si Ming-Sing , Naini Bita V , Venick Robert , Saab Sammy , Wray Christopher L , Ponder Reid , Rosenthal Carl , Klomhaus Alexandra , Böstrom Kristina I , Aboulhosn Jamil A , Kaldas Fady M 
Published: June 2023

ABSTRACTBackgroundThe molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes.MethodsThis retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death.ResultsPatients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development.ConclusionsPatients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.
CytoSIP: An annotated structural atlas for interactions involving cytokine or cytokine receptor
Authors: Wang Lu , Sun Fang , Ma Haojie , Zhong Juanhong , Zhang Huihui , Cheng Siyi , Wu Hao , Wang Nasui , Zhao Mingyi , Zhu Ping , Zheng Heping 
Published: June 2023

AbstractCytokines primarily interact with specific cytokine receptors on the cell surface as essential signal transduction pathways in many physiological and pathological processes. Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling function and have been demonstrated effective in the treatment of many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach to the development of targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, andPhenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. The content of the CytoSIP database includes the following key features: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR at the domain level, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database introduces a unique tri-level SIP data model to link genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Moreover, CytoSIP implements screening criteria and tools to allow customized selection of relevant subset of CK/CKR for the study of interest. This reduces the time and resources needed to interrogate large datasets and allows rapid screening of cytokines and cytokine receptor proteins interfaces for hotspots targeted drug design and any other specific cellular signaling/function mechanisms and their correlation to pathologies. The CytoSIP framework crafted herein bridges CK/CKR genotype with phenotype, facilitating not only the panoramic investigation of the context-dependent crosstalk between CK/CKR but also the development of targeted therapeutic agents. CytoSIP portal website is publicly accessible athttps://CytoSIP.biocloud.top.
Low-frequency somatic mutations are heritable in tropical treesDicorynia guianensisandSextonia rubra
Authors: Schmitt Sylvain , Heuret Patrick , Troispoux Valérie , Beraud Mélanie , Cazal Jocelyn , Chancerel Émilie , Cravero Charlotte , Guichoux Erwan , Lepais Olivier , Loureiro João , Marande William , Martin Olivier , Vincent Gregoire , Chave Jérôme , Plomion Christophe , Leroy Thibault , Heuertz Myriam , Tysklind Niklas 
Published: June 2023

AbstractSomatic mutations potentially play a role in plant evolution, but common expectations pertaining to plant somatic mutations remain insufficiently tested. Unlike in most animals, the plant germline is assumed to be set aside late in development, leading to the expectation that plants accumulate somatic mutations along growth. Therefore, several predictions were made on the fate of somatic mutations: mutations have generally low frequency in plant tissues; mutations at high frequency have a higher chance of intergenerational transmission; branching topology of the tree dictates mutation distribution; and, exposure to UV radiation increases mutagenesis. To provide new insights into mutation accumulation and transmission in plants, we produced two high-quality reference genomes and a unique dataset of 60 high-coverage whole-genome sequences of two tropical tree species,Dicorynia guianensis(Fabaceae) andSextonia rubra(Lauraceae). We identified 15,066de novosomatic mutations inD. guianensisand 3,208 inS. rubra, surprisingly almost all found at low frequency. We demonstrate that: 1) low-frequency mutations can be transmitted to the next generation; 2) mutation phylogenies deviate from the branching topology of the tree; and 3) mutation rates and mutation spectra are not demonstrably affected by differences in UV exposure. Altogether, our results suggest far more complex links between plant growth, ageing, UV exposure, and mutation rates than commonly thought.Significance StatementThe origin and fate of new mutations have received less attention in plants than in animals. Similarly to animals, plant mutations are expected to accumulate with growth and time, and under exposure to UV light. However, contrary to animals, plant reproductive organs form late in an individual’s development, allowing the transmission to the progeny of mutations accumulated along growth. Here, we resequenced DNA from different branches differentially exposed to sunlight of two tropical tree species. We showed that new mutations are generally rare in plant tissues and do not mimic branching patterns but can nevertheless be transmitted to the progeny. Our findings provide a new perspective on heritable plant mutation and its pivotal role as the engine of evolution.
Genome-wide association study of heat stress response inBos taurus
Authors: Czech Bartosz , Wang Yachun 
Published: June 2023

AbstractHeat stress is a major challenge in cattle production, affecting animal welfare, productivity, and the economic viability of the industry. In this study, we conducted a genome-wide association study to identify genetic markers associated with heat stress tolerance in Chinese Holstein cattle. We genotyped 68 cows using Illumina 150K Bovine BeadChip microarray and analyzed 112,081 single nucleotide polymorphisms using a linear model-based GWAS approach. We identified 17 SNPs distributed over three chromosomes that showed statistically significant associations with heat stress tolerance in Chinese Holstein cattle. Five of them were located in introns of two genes,PDZRN4andPRKG1. PDZRN4is involved in protein degradation pathways, whilePRKG1encodes a protein kinase involved in smooth muscle relaxation and blood vessel dilation. Our findings highlight the potential importance ofPDZRN4andPRKG1in heat stress tolerance in cattle and provide valuable genetic markers for further research and breeding programs aimed at improving heat stress tolerance in Holstein cattle. However, further studies are needed to elucidate the exact mechanisms by which these SNPs contribute to heat stress tolerance and their potential implications for practical cattle breeding strategies.
Negative cell cycle regulation by Calcineurin is necessary for proper beta cell regeneration in zebrafish
Authors: Massoz Laura , Bergemann David , Lavergne Arnaud , Reynders Célia , Désiront Caroline , Goossens Chiara , Flasse Lydie , Peers Bernard , Voz Marianne L. , Manfroid Isabelle 
Published: June 2023

AbstractStimulation of pancreatic beta cell regeneration could be a therapeutic lead to treat diabetes. Unlike humans, the zebrafish can efficiently regenerate beta cells, notably from ductal pancreatic progenitors. To gain insight into the molecular pathways involved in this process, we established the transcriptomic profile of the ductal cells after beta cell ablation in the adult zebrafish. These data highlighted the protein phosphatase calcineurin as a new potential modulator of beta cell regeneration. We showed that calcineurin overexpression abolished the regenerative response, leading to glycemia dysregulation. On the opposite, calcineurin inhibition increased ductal cell proliferation and subsequent beta cell regeneration. Interestingly, the enhanced proliferation of the progenitors was paradoxically coupled with their exhaustion. This suggests that the proliferating progenitors are next entering in differentiation. Calcineurin appears as a guardian which prevents an excessive progenitor proliferation to preserve the pool of progenitors. Altogether, our findings reveal calcineurin as a key player in the balance between proliferation and differentiation to enable a proper beta cell regeneration.
The effect of estimation time window length on overlap correction in EEG data
Authors: Skukies René , Ehinger Benedikt V. 
Published: June 2023

AbstractRegression Event-Related-Potentials (ERPs) with overlap correction (also referred to, as linear deconvolution, or temporal response functions) are becoming more popular for the analysis of Electroencephalography (EEG) data. A common question for the analyst is, how to specify the length of the estimation windows. Long estimation windows might capture all relevant event-related activity, but might introduce artifacts due to overfit, short estimation windows might not overfit, but also might not capture all (overlapping) activity, and thereby introduce bias.Using a systematic simulation approach, we show that longer rather than shorter time windows should be preferred for typical EEG designs. We further provide an interactive app to visualize various design parameters:https://estimationwindow.ccn2023.s-ccs.de
Multistability in neural systems with random cross-connections
Authors: Breffle Jordan , Mokashe Subhadra , Qiu Siwei , Miller Paul 
Published: June 2023

AbstractNeural circuits with multiple discrete attractor states could support a variety of cognitive tasks according to both empirical data and model simulations. We assess the conditions for such multistability in neural systems, using a firing-rate model framework, in which clusters of neurons with net self-excitation are represented as units, which interact with each other through random connections. We focus on conditions in which individual units lack sufficient self-excitation to become bistable on their own.Rather, multistability can arise via recurrent input from other units as a network effect for subsets of units, whose net input to each other when active is sufficiently positive to maintain such activity. In terms of the strength of within-unit self-excitation and standard-deviation of random cross-connections, the region of multistability depends on the firing-rate curve of units. Indeed, bistability can arise with zero self-excitation, purely through zero-mean random cross-connections, if the firing-rate curve rises supralinearly at low inputs from a value near zero at zero input. We simulate and analyze finite systems, showing that the probability of multistability can peak at intermediate system size, and connect with other literature analyzing similar systems in the infinite-size limit. We find regions of multistability with a bimodal distribution for the number of active units in a stable state. Finally, we find evidence for a log-normal distribution of sizes of attractor basins, which can appear as Zipf’s Law when sampled as the proportion of trials within which random initial conditions lead to a particular stable state of the system.
Post-acute immunological and behavioral sequelae in mice after Omicron infection
Authors: Ma Tongcui , Suryawanshi Rahul K. , Miller Stephanie R. , Ly Katie K. , Thomas Reuben , Elphick Natalie , Yin Kailin , Luo Xiaoyu , Kaliss Nick , Chen Irene P , Montano Mauricio , Sreekumar Bharath , Standker Ludger , Mu□nch Jan , Damron F. Heath , Palop Jorge J. , Ott Melanie , Roan Nadia R. 
Published: June 2023

ABSTRACTProgress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naïve mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.
Novel Roles for Diacylglycerol in Synaptic Vesicle Priming and Release Revealed by Complete Reconstitution of Core Protein Machinery
Authors: Sundaram R Venkat Kalyana , Chatterjee Atrouli , Bera Manindra , Grushin Kirill , Panda Aniruddha , Li Feng , Coleman Jeff , Lee Seong , Ramakrishnan Sathish , Ernst Andreas M. , Gupta Kallol , Rothman James E. , Krishnakumar Shyam S. 
Published: June 2023

ABSTRACTHere we introduce the full functional reconstitution of genetically-validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca2+. Using this novel setup, we discover new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca2+-triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca2+-dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of ready-release vesicles. Dynamic single-molecule imaging of Complexin binding to ready-release vesicles directly establishes that DAG accelerates the rate of SNAREpin assembly mediated by Munc13 and Munc18 chaperones. The selective effects of physiologically validated mutations confirmed that the Munc18-Syntaxin-VAMP2 ‘template’ complex is a functional intermediate in the production of primed, ready-release vesicles, which requires the coordinated action of Munc13 and Munc18.SIGNIFICANCE STATEMENTMunc13 and Munc18 are SNARE-associated chaperones that act as “priming” factors, facilitating the formation of a pool of docked, release-ready vesicles and regulating Ca2+-evoked neurotransmitter release. Although important insights into Munc18/Munc13 function have been gained, how they assemble and operate together remains enigmatic. To address this, we developed a novel biochemically-defined fusion assay which enabled us to investigate the cooperative action of Munc13 and Munc18 in molecular terms. We find that Munc18 nucleates the SNARE complex, while Munc13 promotes and accelerates the SNARE assembly in a DAG-dependent manner. The concerted action of Munc13 and Munc18 stages the SNARE assembly process to ensure efficient ‘clamping’ and formation of stably docked vesicles, which can be triggered to fuse rapidly (∼10 msec) upon Ca2+influx.