bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics analysis reveals the mechanism of BnC07MYB3a is involved in seed coat color inBrassica napusL
Authors: Hu Ran , Zhang Mengzhen , Shen Shulin , Liu Haijing , Gao Lei , Tian Mengjiao , Liu Yiwei , Wan Huafang , Zhao Huiyan , Yin Nengwen , Du Hai , Liu Liezhao , Lu Kun , Li Jiana , Qu Cunmin 
Published: October 2024

AbstractIn rapeseed (Brassica napus), yellow-seeded varieties accumulate less flavonoid pigments (anthocyanins/proanthocyanidins) in their seed coats compared with black-seeded varieties. The yellow-seeded trait is associated with greatly improved seed oil yield, quality, and commercial value. Many R2R3 MYB activators have been characterized in rapeseed, but how MYB-type repressors affect pigment biosynthesis is not yet fully understood. In this study, we performed transcriptome sequencing and metabolomic analysis ofB. napusvarieties with extreme differences in seed coat color, combined with weighted gene co-expression network analysis. This analysis identified an R2R3-MYB-type transcription factor, BnC07MYB3a (BnaC07G0178800ZS), as a candidate regulator of the yellow-seeded trait inB. napus. OverexpressingBnC07MYB3ainArabidopsis thalianaandB. napusdownregulated the expression of flavonoid biosynthetic genes, resulting in significantly lower anthocyanin and proanthocyanidin accumulation than in the wild-type and a lighter seed coat color in transgenic plants. BnC07MYB3a directly binds to the promoter of theTRANSPARENT TESTA(TT) geneBnTT6and represses its expression. BnC07MYB3a also physically interacts with BnA06bHLH92a and the WD40 transcription factor TRANSPARENT TESTA GLABRA1 (BnTTG1), suggesting that they might form a previously unidentified MYB–bHLH–WD40 transcription factor complex. Our results reveal the molecular mechanism and regulatory network of BnC07MYB3a in determining seed coat color inB. napusand provide a genetic resource for breeding yellow-seeded cultivars ofB. napus.
Dimensionality Reduction of Genetic Data using Contrastive Learning
Authors: Thor Filip , Nettelblad Carl 
Published: October 2024

AbstractWe introduce a framework for using contrastive learning for dimensionality reduction on genetic datasets to create PCA-like population visualizations. Contrastive learning is a self-supervised deep learning method that uses similarities between samples to train the neural network to discriminate between samples. Much of the advances in these types of models have been made for computer vision, but many of the heuristics developed do not translate well from image to genetic data. We define a loss function that outperforms other basic loss functions used in contrastive learning in our experiments, and a data augmentation scheme tailored specifically towards SNP genotype datasets. We compare the performance of our method to PCA and contemporary non-linear methods with respect to how well they preserve local and global structure, and how well they generalize to new data. Our method displays good preservation of global structure and has improved generalization properties over t-SNE, UMAP, and popvae, while preserving relative distances between individuals to a high extent. A strength of the deep learning framework is the possibility of projecting new samples and fine-tuning to new datasets using a pre-trained model without access to the original training data, and the ability to incorporate more domain-specific information in the model. We show examples of population classification on two datasets of dog and human genotypes.
3D genome organization under extreme metabolic adaptation shows variations in genome compartmentalization and looping
Authors: Biswas Tathagata , Li Hua , Rohner Nicolas 
Published: October 2024

AbstractThree-dimensional (3D) genome organization plays a crucial role in gene regulation by influencing cellular functions, such as bringing regulatory elements like enhancers into proximity with their target genes. In this study, we explore variations in 3D genome organization within different morphs of the fishAstyanax mexicanus, which includes a river-dwelling surface fish and multiple cave-dwelling morphs. The cave morphs, also known as cavefish, have adapted to the dark and nutrient-scarce cave environments, resulting in distinct metabolic reprogramming that has made them persistently hyperglycemic, resilient to starvation, and prone to fat accumulation. Focusing on metabolic evolution in cavefish, we used liver tissue to conduct genome-wide contact mapping through Hi-C experiments. Comparing the 3D genome architecture of two cave morphs – Pachón and Tinaja – with that of surface fish, we observed significant changes in genome compartmentalization and genomic loops. Some of these changes were common in both Pachón and Tinaja and were classified as cave-specific looping and compartmental switches. By integrating liver Hi-C data with RNA-seq, ATAC-seq, and histone ChIP-seq datasets, we gained deeper insight into the relationship between cave-specific 3D genome features and the transcriptional activity at associated loci. Additionally, we identified structural variations in the form of common genomic inversions in Pachón and Tinaja compared to surface fish. Therefore, this study is the first to define the 3D genome organization ofAstyanax mexicanusin livers and highlights how adaptation to extreme environments is associated with significant variations in 3D genome architecture, even within the same species.
Robust Detection of Brain Stimulation Artifacts in iEEG Using Autoencoder-Generated Signals and ResNet Classification
Authors: Saal Jeremy , Khambhati Ankit N. , Chang Edward F. , Shirvalkar Prasad 
Published: October 2024

AbstractBackgroundIntracranial EEG (iEEG) is crucial for understanding brain function, but stimulation-induced noise complicates data interpretation. Traditional artifact detection methods require manual user input or struggle with noise variability, especially with limited labeled data.ObjectiveWe developed a supervised method to automatically detect stimulation-induced noise in human iEEG recordings using synthetic data generated by Variational Autoencoders (VAEs) to train a ResNet-18 classifier.MethodsMulti-lead iEEG data were collected, preprocessed, and used to train VAEs for generating synthetic clean and noisy signals. The ResNet-18 model was trained on images of spectra generated from these synthetic signals and validated on real iEEG data from five participants.ResultsThe classifier, trained exclusively on synthetic data, demonstrated high accuracy, precision, and recall when applied to real iEEG recordings, with AUC values greater than 0.99 across all participants.ConclusionWe present a novel approach to effectively detect stimulation-induced noise in iEEG, offering a robust solution for improving data interpretation in scenarios with limited labeled data. Additionally, the pre-trained ResNet-18 model is available for the community to use, facilitating further research and application in similar datasets.
Assessing sustained attention processes and related cerebral activations in typically developing adolescents using the gradual-onset continuous performance task (gradCPT)
Authors: Awada J. , Fernandez NB. , Siffredi V. , Liverani MC. , Miehlbradt J. , Borradori-Tolsa C. , Leuchter R. Ha-Vinh 
Published: October 2024

AbstractIntroductionSustained attention and inhibition processes are fundamental components of attention that mature during adolescence, a transitive period between childhood and adulthood characterized by a rapid behavioral and cognitive development. The current study aimed to provide a better understanding of sustained attention and inhibition processes in typically developing adolescents (n = 26) aged 11-18.MethodsFunctional magnetic resonance images (fMRI) were acquired during two different modalities (thefaceand thescene) from a previously validated gradual□onset continuous (gradCPT) paradigm to evaluate sustained attention performances. In addition, we performed linear regression analyses to investigate how cerebral activation varied as a function of covariates of interest.ResultsWe showed a bilateral fronto-parieto-occipito brain activation during response inhibition regardless the type of task. Participants demonstrated better behavioral performances during thescenegradCPT. We observed a mainly left-lateralized pattern of activation in a fronto-cingulo-cerebellum area during thefacegradCPT and an extended bilateral fronto-temporo-parieto-occipital activation during thescenegradCPT. Finally, we found associations between brain activity and behavioral attentional responses.ConclusionThis study gives a better understanding of the neural correlates of sustained attention and inhibition in a typically developing adolescent population.
Head kinematics associated with off field head injury assessment (HIA1) events in a season of English elite-level club men’s and women’s rugby union matches
Authors: Allan David , Tooby James , Starling Lindsay , Tucker Ross , Falvey Éanna , Salmon Danielle , Brown James , Hudson Sam , Stokes Keith , Jones Ben , Kemp Simon , O’Halloran Patrick , Cross Matt , Bussey Melanie , Tierney Gregory 
Published: October 2024

ABSTRACTObjectivesTo investigate head kinematic variables in elite men’s and women’s rugby union and their ability to predict player removal for an off-field (HIA1) head injury assessment.MethodsInstrumented Mouthguard (iMG) data were collected for 250 men and 132 women from 1,865 and 807 player-matches, respectively, and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA), peak resultant angular acceleration (PAA) and peak change in angular velocity (dPAV) were extracted from each head acceleration event (HAE). HAEs were linked to documented HIA1 events, with ten logistical regression models for men and women, using a random subset of non-case HAEs, calculated to identify kinematic variables associated with HIA1 events. Receiver operating characteristic curves (ROC) were used to describe thresholds for HIA1 removal.ResultsIncreases in PLA, and dPAV were significantly associated with an increasing likelihood of HIA1 removal in the men’s game, with an OR ranging from 1.05-1.12 and 1.13-1.18, respectively. The optimal values to maximise for both sensitivity and specificity for detecting an HIA1 were 1.96krad.s-2, 24.29g, and 14.75rad.s-1for PAA, PLA, and dPAV respectively. Only one model had any significant variable associated with increasing the likelihood of a HIA1 removal in the women’s game – PAA with an OR of 8.51 (1.23-58.66). The optimal values for sensitivity and specificity for women were 2.01krad.s-2, 25.98g, and 15.38rad.s-1for PAA, PLA, and dPAV respectively.ConclusionPLA and dPAV were predictive of men’s HIA1 events. Further HIA1 data are needed to understand the role of head kinematic variables in the women’s game. The calculated spectrum of sensitivity and specificity of iMG alerts for HIA1 removals in men and women present a starting point for further discussion about using iMGs as an additional trigger in the existing HIA process.Key PointsConcussion is the most common injury in rugby union. Current on-field suspected concussion detection methods rely on visually identifying an athlete exhibiting concussion signs, reporting symptoms or identifying clinical features in real time or upon video review of the event.Increases in peak linear acceleration (PLA) and changes in Peak Angular Velocity (dPAV) were predictive of men’s Head Injury Assessment 1 (HIA1) events, and Peak Angular Acceleration (PAA) was predictive of women’s HIA1 events; however, further HIA1 data are needed to fully understand the role of head kinematic variables within the women’s game.The findings contributed to the evidence that informed the 2024 World Rugby policy change to include instrumented mouthguards (iMG) measurements as a trigger for the HIA1 removal process in the elite adult game.
The Spc105Knl1/Kre28Zwintcomplex promotes mitotic error correction by outer kinetochore recruitment of the Ipl1Aurora Bkinase
Authors: Dudziak Alexander , Schmidt Jasmin , Hamm Frederik , Tendulkar Sharvari , Jänen Karolin , Vetter Ingrid R. , Singh Sylvia , Fischböck Josef , Herzog Franz , Westermann Stefan 
Published: October 2024

AbstractKinetochores link chromosomes to dynamic microtubules of the mitotic spindle. To ensure equal chromosome segregation, sister chromatids must attach to microtubules from opposing spindle poles, a configuration referred to as biorientation. To avoid chromosome missegregation the conserved kinase Aurora B phosphorylates outer kinetochore proteins on attachments lacking tension, allowing re-establishment of new connections until biorientation is achieved. While Aurora B localizes to the centromere and inner kinetochore as part of the chromosomal passenger complex (CPC), the underlying recruitment pathways can be eliminated without fully disrupting biorientation. It therefore remains unclear how the kinase operates during error correction and whether additional mechanisms may facilitate tension-dependent phosphorylation of substrate proteins.In this study, we identify the conserved KMN subcomplex Spc105Knl1/Kre28Zwintas an outer kinetochore receptor of the Aurora kinase Ipl1 inSaccharomyces cerevisiae. We show that mutations in the helical bundle domain of Spc105/Kre28 cause defective mitotic error correction, closely resembling the effects ofipl1orsli15mutants. In biochemical experiments we show that Ipl1/Sli15 directly associates with the KMN network via the Spc105/Kre28 subcomplex and that binding is inhibited by Ipl1 autophosphorylation. The phenotype of thekre28mutant cells can be efficiently suppressed by artificial recruitment of Ipl1, demonstrating the importance of Ipl1 docking to the outer kinetochore. These results have important implications for the mechanism of tension-dependent error correction during chromosome biorientation.
Computing the Human Interactome
Authors: Zhang Jing , Humphreys Ian R. , Pei Jimin , Kim Jinuk , Choi Chulwon , Yuan Rongqing , Durham Jesse , Liu Siqi , Choi Hee-Jung , Baek Minkyung , Baker David , Cong Qian 
Published: October 2024

AbstractProtein-protein interactions (PPI) are essential for biological function. Recent advances in coevolutionary analysis and Deep Learning (DL) based protein structure prediction have enabled comprehensive PPI identification in bacterial and yeast proteomes, but these approaches have limited success to date for the more complex human proteome. Here, we overcome this challenge by 1) enhancing the coevolutionary signals with 7-fold deeper multiple sequence alignments harvested from 30 petabytes of unassembled genomic data, and 2) developing a new DL network trained on augmented datasets of domain-domain interactions from 200 million predicted protein structures. These advancements allow us to systematically screen through 200 million human protein pairs and predict 18,316 PPIs with an expected precision of 90%, among which 5,578 are novel predictions. 3D models of these predicted PPIs nearly triple the number of human PPIs with accurate structural information, providing numerous insights into protein function and mechanisms of human diseases.
PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasitePlasmodium falciparum
Authors: Rawat Akanksha , Antil Neelam , Meenakshi  , Deshmukh Bhagyashree , Rai Akhila Balakrishna , Kumar Narendra , Prasad T.S. Keshava , Karmodiya Krishanpal , Sharma Pushkar 
Published: October 2024

AbstractMalaria parasite transits through distinct developmental stages during its life cycle in the human and mosquito host, which includes unique asynchronous division in the erythrocytes. The switch from its asexual stage to sexual forms, which is critical for disease transmission, is intricately regulated but signalling pathways involved in this process have remained unknown. In the present study, we report a novel signalling pathway involving Protein Phosphatase PfPPM2, which regulates asexual division of the parasite as well as its conversion to sexual forms. Phosphoproteomics revealed that PfPPM2 may regulate the phosphorylation of key proteins involved in chromatin remodelling and protein translation. One of the key PfPPM2-targets that emerged from these studies was Heterochromatin Protein 1 (HP1), a regulator of heritable gene silencing which contributes to both mitotic proliferation as well as sexual commitment of the parasite. We demonstrate that PfPPM2 promotes sexual conversion by regulating the interaction between HP1, H3K9me3 and chromatin and it achieves this by dephosphorylating S33 of HP1. Regulation of HP1 and Histone H3 by PfPPM2 may also contribute to division. In addition, PfPPM2 also regulates protein synthesis in the parasite by repressing the phosphorylation of initiation factor eIF2α, which is likely to contribute to parasite division and possibly sexual differentiation.
Age-related increases in PDE11A4 protein expression trigger liquid:liquid phase separation (LLPS) of the enzyme that can be reversed by PDE11A4 small molecules inhibitors
Authors: Amurrio E , Patel J , Danaher M , Goodwin M , Kargbo P , Lin S , Hoffman CS , Ul Mahmood S , Rotella DP , Kelly MP 
Published: October 2024

ABSTRACTPDE11A is a little-studied phosphodiesterase sub-family that breaks down cAMP/cGMP, with the PDE11A4 isoform being enriched in the memory-related brain region called the hippocampus. Age-related increases in PDE11A expression occur in human and rodent hippocampus and cause age-related cognitive decline of social memories. Interestingly, the age-related increase in PDE11A4 protein ectopically accumulates in spherical clusters that group together in the brain to form linear filamentous patterns termed “ghost axons.” The biophysical/physiochemical mechanisms underlying this age-related clustering of PDE11A4 are not yet known. As such, we determine here if age-related clustering of PDE11A4 may reflect liquid:liquid phase separation (LLPS), and if PDE11A inhibitors being developed for age-related cognitive decline can reverse this biomolecular condensation. We found that human and mouse PDE11A4 exhibit several LLPS-promoting sequence features including intrinsically disordered regions, non-covalent pi-pi interactions, and prion-like domains, with multiple bioinformatic tools predicting PDE11A4 undergoes LLPS. Consistent with these predictions, age-related PDE11A4 clusters were non-membrane bound spherical droplets that progressively fuse over time in a concentration-dependent manner. 5 different PDE11 inhibitors (tadalafil, BC11-38, SMQ-02-57, SMQ-03-30 and SMQ-03-20) across 3 scaffolds reversed PDE11A4 LLPS (a.k.a. remixing) in hippocampal HT22 cells, with PDE11A4 droplets reforming (a.k.a. de-mixing) following a 5-hour washout of low but not high concentrations of these compounds. Strikingly, a single oral administration of 30 mg/kg SMQ-03-20 substantially reduced the presence of PDE11A4 ghost axon in the aged mouse brain. Thus, PDE11A4 exhibits 4 defining criteria of LLPS, and PDE11A small molecule inhibitors reverse this age-related phenotype bothin vitroandin vivo.
Diverse calcium dynamics underlie place field formation in hippocampal CA1 pyramidal cells
Authors: Sumegi Mate , Olah Gaspar , Lukacs Istvan Paul , Blazsek Martin , Makara Judit K. , Nusser Zoltan 
Published: October 2024

AbstractEvery explored environment is represented in the hippocampus by the activity of distinct populations of pyramidal cells (PCs) that typically fire at specific locations called their place fields (PFs). PFs are constantly born even in familiar surroundings (during representational drift), and many rapidly emerge when the animal explores a new or altered environment (during global or partial remapping). Behavioral time scale synaptic plasticity (BTSP), a plasticity mechanism based on prolonged somatic bursts induced by dendritic Ca2+plateau potentials, was recently proposed as the main cellular mechanism underlying new PF formations (PFF), but it is unknown whether burst-associated large somatic [Ca2+] transients are necessary and/or sufficient for PFF. To address this issue, here we performedin vivotwo-photon [Ca2+] imaging of hippocampal CA1 PCs in head-restrained mice to investigate somatic [Ca2+] dynamics underlying PFFs in familiar and novel virtual environments. Our results demonstrate that although many PFs are formed by BTSP-like events, PFs also frequently emerge with initial [Ca2+] dynamics that do not match any of the characteristics of BTSP. BTSP and non-BTSP-like new PFFs occur spontaneously in familiar environments, during neuronal representational switches and instantaneously in new environments. Our data also reveal that solitary [Ca2+] transients that exceed in amplitude those evoking BTSP-like PFFs frequently occur without inducing PFs, demonstrating that large [Ca2+] transientsper seare not sufficient for PFF.
The role of cytochrome c in mitochondrial metabolism of human oocytes
Authors: Surmacki Jakub Maciej , Abramczyk Halina , Sobkiewicz Bogna , Walczak-Jędrzejowska Renata , Słowikowska-Hilczer Jolanta , Marchlewska Katarzyna 
Published: October 2024

AbstractWe investigated the biochemical composition of specific organelles in human oocyte cells at various maturation stages (GV, immature MI, MII with the first polar body, MII with giant polar body, and vacuoles) using Raman imaging. The structures analyzed included the nucleus, zona pellucida, perivitelline space, polar body, mitochondria, and cytoplasm. Raman imaging combined with chemometric classification via Cluster Analysis facilitated a comprehensive biochemical analysis of the proteomic, lipidomic, and DNA profiles of the human oocyte. Our findings indicate that cytochromecis a crucial protein in oocyte mitochondria, essential for both cellular respiration (via oxidative phosphorylation) and apoptosis. Effective oocyte cell functioning requires cytochromecin its redox-balanced forms: reduced and oxidized. The oxidized form of cytochromecplays a pivotal role in the electron transport chain, enabling proper electron shuttling between complex III, cytochromec, and complex IV. This process ensures controlled oxidative phosphorylation and ATP production, which are vital for most steps in oocyte maturation.BackgroundIn spite of progress in the identification of the fertile/infertile human oocytes in the recent decades, our understanding of molecular mechanisms occurring in the female reproductive cells did not make significant progress.ObjectiveThe present study aimed to develop our knowledge on mitochondrial metabolism in oocyte cells.ResultsBiochemical human oocyte analysis of proteomic-lipidomic-DNA profile by using Raman imaging combined with chemometric classification method of Cluster Analysis has been obtained. Our results show that cytochromecis a key protein in oocyte mitochondria that is needed to maintain life (respiration via oxidative phosphorylation) and cell death (apoptosis).Materials and MethodsIn this experimental study, the nine fresh human native live oocytes from six donors collected in Salve Medica, Lodz, Poland have been investigated. The fingerprint and high-frequency region were evaluated by using Raman spectroscopy and imaging from 400 to 3500 cm-1. The principal component analysis method was used to visualize the difference in the Raman spectra of oocytes at different stage of maturation. The study was approved by the Bioethical Committee of the Medical University in Lodz, Poland (No RNN/83/23/KE). Written informed consent was obtained from all patients who voluntarily participated in the study. All procedures were conducted in accordance with the guidelines of the Declaration of Helsinki (2013).Abstract Figure