bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep increases firing rate modulation during interictal epileptic activities in mesial temporal structures
Authors: Whitmarsh Stephen , Nguyen-Michel Vi-Huong , Lehongre Katia , Mathon Bertrand , Adam Claude , Lambrecq Virginie , Frazzini Valerio , Navarro Vincent 
Published: December 2022

AbstractEpileptic seizures and interictal epileptiform discharges (IEDs) are strongly influenced by sleep and circadian rhythms. However, human data on the effect of sleep on neuronal behavior during interictal activity have been lacking. We analyzed EEG data from epileptic patients implanted with macro and micro electrodes targeting mesial temporal structures. Sleep staging was performed on concomitantly recorded polysomnography and video-EEG. Automated IED detection identified thousands of IEDs per patient. Both the rate and amplitude of IEDs were increased with deeper stages of NREM sleep. Single unit activity (SUA) and multi-unit activity (MUA) increased their firing during the IED spike, and strongly decreased during the subsequent slow wave. These time-locked firing rate modulations were shown to increase during deeper stages of NREM sleep. Finally, during resting behaviour, neuronal firing rate, bursting rate and firing regularity were all shown to progressively decrease with deeper stages of NREM sleep.
Specificity, synergy, and mechanisms of splice-modifying drugs
Authors: Ishigami Yuma , Wong Mandy S. , Martí-Gómez Carlos , Ayaz Andalus , Kooshkbaghi Mahdi , Hanson Sonya , McCandlish David M. , Krainer Adrian R. , Kinney Justin B. 
Published: December 2022

AbstractDrugs that target pre-mRNA splicing hold great therapeutic potential, but the quantitative understanding of how these drugs work is limited. Here we introduce mechanistically interpretable quantitative models for the sequence-specific and concentration-dependent behavior of splice-modifying drugs. Using massively parallel splicing assays, RNA-seq experiments, and precision dose-response curves, we obtain quantitative models for two small-molecule drugs, risdiplam and branaplam, developed for treating spinal muscular atrophy. The results quantitatively characterize the specificities of risdiplam and branaplam for 5’ splice site sequences, suggest that branaplam recognizes 5’ splice sites via two distinct interaction modes, and disprove the prevailing two-site hypothesis for risdiplam activity atSMN2exon 7. The results also show that anomalous single-drug cooperativity, as well as multi-drug synergy, are widespread among small-molecule drugs and antisense-oligonucleotide drugs that promote exon inclusion. Our quantitative models thus clarify the mechanisms of existing treatments and provide a basis for the rational development of new therapies.
Interplay between acetylation and ubiquitination of imitation switch chromatin remodeler Isw1 confers multidrug resistance inCryptococcus neoformans
Authors: Meng Yang , Li Zhuoran , Jiang Tianhang , Sun Tianshu , Li Yanjian , Gao Xindi , Li Hailong , Suo Chenhao , Li Chao , Yang Sheng , Lan Tian , Liao Guojian , Liu Tong-Bao , Wang Ping , Ding Chen 
Published: December 2022

AbstractCryptococcus neoformansposes a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for multidrug resistance inC. neoformans. Cells with the disruptedISW1gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1K97coordinates with its ubiquitination processes at Isw1K113and Isw1K441through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates ofC. neoformansoverexpressing the degradation-resistantISW1K97Qallele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation-Isw1-ubiquitination regulation axis that controls multidrug resistance inC. neoformans.
Annotating metabolite mass spectra with domain-inspired chemical formula transformers
Authors: Goldman Samuel , Wohlwend Jeremy , Stražar Martin , Haroush Guy , Xavier Ramnik J. , Coley Connor W. 
Published: December 2022

AbstractMetabolomic studies have succeeded in identifying small molecule metabolites that mediate cell signaling, competition, and disease pathology in part due to large-scale community efforts to measure mass spectra for thousands of metabolite standards. Nevertheless, the vast majority of spectra observed in clinical samples cannot be unambiguously matched to known structures, suggesting powerful opportunities for further discoveries in the dark metabolome. Deep learning approaches to small molecule structure elucidation have surprisingly failed to rival classical statistical methods, which we hypothesize is due to the lack of in-domain knowledge incorporated into current neural network architectures. We introduce a new neural network driven workflow for untargeted metabolomics, Metabolite Inference with Spectrum Transformers (MIST), to annotate mass spectrometry peaks with chemical structures generalizing beyond known standards. Unlike other neural approaches, MIST incorporates domain insights into its architecture by forcing the network to more directly link peaks to physical atom representations, neutral losses, and chemical substructures. MIST outperforms both standard neural architectures and the state-of-the-art kernel method on fingerprint prediction from spectra for over 70% of metabolite standards and retrieves over 66% of metabolites with equal or improved accuracy, with 29% strictly better. We further demonstrate the utility of MIST in a prospective setting to identify new differentially abundant metabolite structures from an inflammatory bowel disease patient cohort and subsequently annotate dipeptides and alkaloid compounds without spectral standards.
Alternative Complement Pathway Regulates Thermogenic Fat Function via Adipsin and Adipocyte-derived C3aR1 in a Sex-dependent Fashion
Authors: Ma Lunkun , Gilani Ankit , Rubio-Navarro Alfonso , Cortada-Almar Eric , Li Ang , Reilly Shannon M. , Tang Liling , Lo James C. 
Published: December 2022

AbstractThermogenesis in beige/brown adipose tissues can be leveraged to combat metabolic disorders such as type 2 diabetes and obesity. The complement system plays pleiotropic roles in metabolic homeostasis and organismal energy balance with canonical effects on immune cells and non-canonical effects on non-immune cells. The adipsin/C3a/C3aR1 pathway stimulates insulin secretion and sustains pancreatic beta cell mass. However, its role in adipose thermogenesis has not been defined. Here, we show thatAdipsinknockout mice exhibit increased energy expenditure and white adipose tissue (WAT) browning. C3a, a downstream product of adipsin, is generated from complement component 3 and decreasesUcp1expression in subcutaneous adipocytes. In addition, adipocyte-specificC3aR1knockout male mice show enhanced WAT thermogenesis and increased respiration. In stark contrast, adipocyte-specificC3aR1knockout female mice display decreased brown fat thermogenesis and are cold intolerant. Female mice express lower levels ofAdipsinin thermogenic adipocytes and adipose tissues than males.C3aR1is also lower in female subcutaneous adipose tissue than males. Collectively, these results reveal sexual dimorphism in the adipsin/C3a/C3aR1 axis in regulating adipose thermogenesis. Our findings establish a newly discovered role of the alternative complement pathway in adipose thermogenesis and highlight sex-specific considerations in potential therapeutic targets for metabolic diseases.
The bHLH-PAS transcriptional complex Sim:Tgo plays active roles in late oogenesis to promote follicle maturation and ovulation
Authors: Oramas Rebecca , Knapp Elizabeth , Zeng Baosheng , Sun Jianjun 
Published: December 2022

AbstractAcross species, ovulation is a process induced by a myriad of signaling cascades that ultimately results in activation of proteolytic enzymes and degradation of the follicle wall to release encapsulated oocytes. Follicles need to first mature and gain ovulatory competency before ovulation. However, the signaling pathways regulating follicle maturation are incompletely understood inDrosophilaand other species. Our previous work showed that bHLH-PAS transcription factor Single-minded (Sim) likely plays important roles for follicle maturation downstream of the NR5A-family nuclear receptor Ftz-f1 inDrosophila. Here, we explore the mechanism of Sim-regulated follicle maturation. We demonstrate that Tango (Tgo), another bHLH-PAS protein acts as a cofactor of Sim to promote follicle cell differentiation from stages 10 to 12. In addition, we discovered that re-upregulation of Sim in stage-14 follicle cells is also essential to promote ovulatory competency by upregulating octopamine receptor in mushroom body (OAMB), matrix metalloproteinase 2 (Mmp2), and NADPH oxidase (NOX), either independent of or in conjunction with the zinc-finger protein Hindsight (Hnt). All of these factors are critical for successful ovulation. Together, our work indicates that the transcriptional complex Sim:Tgo plays multiple roles in late-stage follicle cells to promote follicle maturation and ovulation.
Dynamic decomposition of transcriptome responses during plant effector-triggered immunity revealed conserved responses in two distinct cell populations
Authors: Liu Xiaotong , Igarashi Daisuke , Hillmer Rachel A. , Stoddard Thomas , Lu You , Tsuda Kenichi , Myers Chad L. , Katagiri Fumiaki 
Published: December 2022

SummaryRapid plant immune responses in the appropriate cells are needed for effective defense against pathogens. Although transcriptome analysis is often used to describe overall immune responses, collecting transcriptome data with sufficient resolution in both space and time is challenging.We reanalyzed public Arabidopsis time-course transcriptome data obtained after a low-dose inoculation of aPseudomonas syringaestrain expressing the effector AvrRpt2, which induces Effector-Triggered Immunity (ETI) in Arabidopsis. Double-peak time-course patterns were prevalent among thousands of upregulated genes. We implemented a multi-compartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each gene.The decomposed peaks revealed an “echoing” pattern: the peak times of the first and second peaks correlated well across most upregulated genes. We demonstrated that two peaks likely represent responses of two distinct cell populations, which respond either cell-autonomously or indirectly to AvrRpt2. Thus, the peak decomposition extracted spatial information from the time-course data.The echoing pattern also indicated a conserved transcriptome response between two cell populations despite different elicitor types. WRKY transcription factors appeared to underlie the conserved transcriptome response. Activation of a WRKY network via different entry-point WRKYs could explain the conserved transcriptome response elicited by different elicitor types.
Biomechanical modeling of Border Collies (Canis familiaris) for insights of tail and limb use during the aerial phase of jumping
Authors: Rottier Tom , Schulz Andrew K. , Söhnel Katja , Mccarthy Kathryn , Fischer Martin S. , Jusufi Ardian 
Published: December 2022

AbstractDogs and other members of Canidae utilize their tails for different purposes, including agile movements, such as running and jumping. In this study, we utilized motion capture biomechanical data of a border collie executing an agile rotational jump maneuver. This data created a 17-segment biomechanical model of the border collie’s (Canis familiaris)limb movement during agile jumps. This model was verified by comparing it to the biomechanical movement and fitting the dog’s agile task with an RMSE less than 2.5%. Using this joint model, we held specific segments constant to view their inertial impact on the dog during the aerial phase of jumping. Results suggest that the tail, hind limbs, and fore limb provides little to no inertial advantage during these rotational jump maneuvers. The tail of dogs likely does have a minimal impact on inertia, the opposite of animals like the gecko. This work could alleviate unknown biomechanical use of the tails to understand the behavioral biomechanics of lesser-known species in their ability to use their tail for rapid and taxing behaviors, including sprinting or climbing.
Oat species and interspecific amphiploids show predominance of diploid nuclei in the syncytial endosperm
Authors: Tomaszewska Paulina , Kosina Romuald 
Published: January 2023

AbstractApart from apomictic types, thePolygonum-type eight-nuclear embryo sac is considered to be dominant in grasses. A triploid endosperm is formed as a result of double fertilisation. This study showed, for the first time, the dominance of diploid nuclei in the syncytial stage of the central cell of embryo sac in oat species and amphiploids. The dominance of diploid nuclei, which were the basis for the formation of polyploid nuclei, was weaker in amphiploids due to aneuploid events. The genomicin situhybridisation method applied in the study did not distinguish the maternal and paternal haploid nuclei of embryo sac. However, this method demonstrated the lack of a set of genomes of one haploid nucleus. It can be assumed that the formation of diploid oat endosperm occurred after the fusion of one polar nucleus and the nucleus of a sperm cell, while the second polar nucleus formed 1nnuclei. The levels of syncytial ploidy were not influenced by both aneuploid events and correlated with pollen developmental anomalies. The differences in the analysed cytogenetic events distinguished amphiploids and their parental species in the ordination space.
AntiRef: reference clusters of human antibody sequences
Authors: Briney Bryan 
Published: December 2022

AbstractMotivationBiases in the human antibody repertoire result in publicly available antibody sequence datasets containing many duplicate or highly similar sequences. These redundant sequences are a barrier to rapid similarity searches and reduce the efficiency with which these datasets can be used to train statistical or machine learning models of human antibodies. Identity-based clustering provides a solution; however, the extremely large size of available antibody repertoire datasets makes such clustering operations computationally intensive and potentially out of reach for many scientists and researchers who would benefit from such data.ResultsAntiRef (Antibody Reference Clusters), which is modeled after UniRef, provides clustered datasets of filtered human antibody sequences. Due to the modular nature of recombined antibody genes, the clustering thresholds used by UniRef to cluster general protein sequences (100, 90, and 50 percent identity) are suboptimal for antibody clustering. Starting from a dataset of ∼451 million full-length, productive human antibody sequences from the Observed Antibody Space (OAS) repository, AntiRef provides antibody sequence datasets clustered at a range of identity thresholds better suited to antibody sequences. AntiRef90, which uses the least stringent clustering threshold, is roughly one-third the size of the input dataset and less than half the size of the non-redundant AntiRef100.AvailabilityAntiRef is freely available via Zenodo (zenodo.org/record/7474336) under the CC-BY 4.0 license, which matches the licensing of OAS datasets. All code used to download and filter sequences, generate AntiRef clusters, and create the figures used in this publication is freely available under the MIT license via GitHub (github.com/briney/antiref). We anticipate AntiRef updates will be released bi-annually, with the option for supplementary out-of-band updates when large or particularly interesting datasets are made available. The AntiRef versioning scheme (current version: v2022.12.14) refers to the date on which sequences were retrieved from OAS.Contactbriney@scripps.edu
Traumatic brain injury induced microglial and Caspase3 activation in the retina
Authors: Kovács-Öller Tamás , Zempléni Renáta , Balogh Boglárka , Szarka Gergely , Fazekas Bálint , Tengölics Ádám J , Amrein Krisztina , Czeiter Endre , Hernádi István , Büki András , Völgyi Béla 
Published: December 2022

AbstractTraumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damages induced by repetitive injuries occurring in the brain are more common, especially amongst athletes. rmTBI can also have a detrimental effect on the retina and the pathophysiology of these injuries are likely to differ from the severe TBI (sTBI) retinal injury.Here we showed how rmTBI and sTBI can dissimilarly affect the retina. Our results indicate an increase in the number of activated microglial cells and Caspase3-positive cells in the retina in both traumatic models, suggesting a rise in the level of inflammation and cell death after TBI. The pattern of microglial activation appears evenly distributed and widespread but differs amongst the various retinal layers. sTBI induced microgial activation in both the superficial and deep retinal layers. In contrast to sTBI, no significant change occurred following the repetitive mild injury in the superficial layer, only the deep layer (spanning from the inner nuclear layer to the outer plexiform layer) shows microglial activation. This difference suggests that alternate response mechanisms play a role in the case of the different TBI incidents. The Caspase3 activation pattern showed a uniform increase in both the superficial and deep layers of the retina. This suggests a different action in the course of the disease in sTBI and rmTBI models and points to the need for new diagnostic procedures. Our present results suggest that the retina might serve as such a model of head injuries since the retinal tissue reacts to both forms of TBI and is the most accessible part of the human brain.
Hematopoietic-specific heterozygous loss ofDnmt3aexacerbates colitis-associated colon cancer
Authors: Feng Yang , Newsome Rachel C , Robinson Troy , Bowman Robert L , Zuniga Ashley N , Hall Kendra N , Bernsten Cassandra M , Shabashvili Daniil E , Krajcik Kathryn I , Gunaratne Chamara , Zaroogian Zachary J , Venugopal Kartika , Casellas Roman Heidi L , Levine Ross L , Chatila Walid K , Yaeger Rona , Riva Alberto , Kopinke Daniel , Jobin Christian , Avram Dorina , Guryanova Olga A 
Published: December 2022

ABSTRACTClonal hematopoiesis (CH) is defined as clonal expansion of mutant hematopoietic stem cells absent diagnosis of a hematologic malignancy. Presence of CH in solid tumor patients, including colon cancer, correlates with shorter survival. We hypothesized that bone marrow-derived cells with heterozygous loss-of-function mutations ofDNMT3A, the most common genetic alteration in CH, contribute to the pathogenesis of colon cancer.In a mouse model that combines colitis-associated colon cancer with experimental CH driven byDnmt3a+/Δ, we found higher tumor penetrance and increased tumor burden compared to controls. Histopathological analysis revealed accentuated colonic epithelium injury, dysplasia and adenocarcinoma formation. Transcriptome profiling of colon tumors identified enrichment of gene signatures associated with carcinogenesis, including angiogenesis. Treatment with the angiogenesis inhibitor axitinib eliminated the colon tumor-promoting effect of experimental CH driven byDnmt3ahaploinsufficiency. This study provides conceptually novel insights into non-tumor-cell-autonomous effect of hematopoietic alterations on colon carcinogenesis and identifies potential therapeutic strategies.SUMMARYA pre-clinical mouse model demonstrates that genetic alterations in the blood system characteristic of clonal hematopoiesis (CH) contribute to an aggressive solid tumor phenotype. It further identifies cancer angiogenesis as a potential therapeutic target to mitigate adverse CH effects.
Garments that measure EEG: Evaluation of an EEG sensor layer fully implemented with smart textiles
Authors: López-Larraz Eduardo , Escolano Carlos , Robledo Almudena , Morlas Leyre , Alda Alexandra , Minguez Javier 
Published: January 2023

AbstractThis paper presents the first garment capable of measuring EEG activity with accuracy comparable to state-of-the art dry EEG systems. The main innovation is an EEG sensor layer (i.e., the electrodes, the signal transmission, and the cap support) fully implemented as a garment, using threads, fabrics and smart textiles, without relying on any metal or plastic materials. The garment is interfaced via a connector to a mobile EEG amplifier to complete the measurement system. The new EEG system (Garment-EEG) has been characterized with respect to a state-of-the-art Ag/AgCl dry-EEG system (Dry-EEG) over the forehead area of healthy participants in terms of: (1) skin-electrode impedance; (2) electrophysiological measurements (spontaneous and evoked EEG activity); (3) artifacts; and (4) user ergonomics and comfort. The results show that the Garment-EEG system provides comparable recordings to Dry-EEG, but it is more prone to getting affected by artifacts in adverse recording conditions due to poorer contact impedances. Ergonomics and comfort favor the textile-based sensor layer with respect to its metal-based counterpart. User acceptance is the main obstacle for EEG systems to democratize neurotechnology and non-invasive brain-computer interfaces. EEG sensor layers encapsulated in wearables have the potential to enable neurotechnology that is naturally accepted by people in their daily lives. Furthermore, by supporting the EEG implementation in the textile industry it is manufactured with lower cost and much less pollution compared to the metal and plastic industries.