bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decomposed frontal corticostriatal ensemble activity changes across trials, revealing distinct features relevant to outcome-based decision making
Authors: Handa Takashi , Fukai Tomoki , Kurikawa Tomoki 
Published: March 2024

AbstractThe frontal cortex-striatum circuit plays a pivotal role in adaptive goal-directed behaviours. However, the mediation of decision-related signals through cross-regional transmission between the medial frontal cortex and the striatum by neuronal ensembles remains unclear. We analysed neuronal ensemble activity obtained through simultaneous multiunit recordings in the secondary motor cortex (M2) and dorsal striatum (DS) while the rats performed an outcome-based choice task. Tensor component analysis (TCA), an unsupervised dimensionality reduction approach at the single-trial level, was adopted for concatenated ensembles of M2 and DS neurons. We identified distinct three spatiotemporal neural dynamics (TCA components) at the single-trial level specific to task-relevant variables. Choice-position selective neural dynamics was correlated with the trial-to-trial fluctuation of behavioural variables. This analytical approach unveiled choice-pattern selective neural dynamics distinguishing whether the incoming choice was a repetition or switch from the previous choice. Other neural dynamics was selective to outcome. Choice-pattern selective within-trial activity increased before response choice, whereas outcome selective within-trial activity increased following response. These results suggest that the concatenated ensembles of M2 and DS process distinct features of decision-related signals at various points in time. The M2 and DS may collaboratively monitor action outcomes and determine the subsequent choice, whether to repeat or switch, for coordinated action selection.
Exploring the impact of sequence context on errors in SNP genotype calling with Whole Genome Sequencing data using AI-based autoencoder approach
Authors: Kotlarz Krzysztof , Mielczarek Magda , Biecek Przemysław , Guldbrandtsen Bernt , Szyda Joanna 
Published: March 2024

ABSTRACTA critical step in the analysis of WGS data is variant calling. Despite its importance, variant calling is prone to errors. Our study investigated the association between incorrect SNP and variant quality metrics and nucleotide context. In our study, incorrect SNPs were defined in twenty Holstein-Friesian cows by comparing their SNPs genotypes identified by whole genome sequencing with the IlluminaNovaSeq6000 and the EuroGMD50K genotyping microarray. The data set was divided into the correct set of SNPs (666,333 SNPs) and the incorrect set of SNPs (4,557 SNPs). The training data set consisted of only the correct SNPs, while the test data set contained a balanced mix of all the incorrectly and correctly called SNPs. An autoencoder was constructed to identify systematically incorrect SNPs that were marked as outliers by a one-class support vector machine and isolation forest algorithms. The results showed that 59.53% (±0.39%) of the incorrect SNPs had systematic patterns, with the remainder being random errors. The frequent occurrence of the CGC trimer was due to mislabeling a call for C. Incorrect T instead A call was associated with the presence of T in the neighboring downstream position. These errors may arise due to the fluorescence patterns of nucleotide labelling.
EXPLORING THE DISTRIBUTION OF SINGLE NUCLEOTIDE POLYMORPHISMS ACROSS HUMAN EXONS AND INTRONS
Authors: Fraszczak Magdalena , Liu Jakub , Mielczarek Magda , Dobosz Paula , Szyda Joanna 
Published: March 2024

ABSTRACTAmong all types of mutations, single nucleotide polymorphisms are the most common type of genomic variation. In our study, we explore the counts of single nucleotide polymorphisms in particular exons and introns of the human genome based on the data set of 1,222 individuals of Polish origin that comprises 41,836,187 polymorphisms. In particular, chromosomes 1 and 22 were considered as representatives of two markedly different DNA molecules, since HSA01 represents the longest and HSA22 is one of the shortest chromosomes. The results demonstrate that outer (first, last) exons as well as the first introns harbour significantly more SNPs than other genic regions. The observed differences in counts reflect the distinct functional roles of those genomic units.
Puberty Blocker and Aging Impact on Testicular Cell States and Function
Authors: Murugesh Varshini , Ritting Megan , Salem Salem , Aalam Syed Mohammed Musheer , Garcia Joaquin , Chattha Asma J , Zhao Yulian , Knapp David JHF , Kalthur Guruprasad , Granberg Candace F , Kannan Nagarajan 
Published: March 2024

AbstractSpermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as ‘puberty blocker’ (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete ’reversibility’ and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.
Aging impacts basic auditory and timing processes
Authors: Criscuolo Antonio , Schwartze Michael , Bonetti Leonardo , Kotz Sonja A. 
Published: March 2024

AbstractDeterioration in the peripheral and central auditory systems is common in older adults and often leads to hearing and speech comprehension difficulties. Even when hearing remains intact, electrophysiological data of older adults frequently exhibit altered neural responses along the auditory pathway, reflected in variability in phase alignment of neural activity to speech sound onsets. However, it remains unclear whether these challenges in speech processing in aging stem from more fundamental deficits in auditory and timing processes. Here, we investigatedifandhowaging individuals encoded temporal regularities in isochronous auditory sequences presented at 1.5Hz, andifthey employed adaptive mechanisms of neural phase alignment in anticipation of next sound onsets. We recorded EEG in older and young individuals listening to simple isochronous tone sequences. We show that aging individuals displayed increased amplitudes and variability in time-locked responses to sounds, an increased 1/F slope, but reduced phase-coherence in the delta and theta frequency-bands. These observations suggest a lack of repetition-suppression and inhibition when processing repeated and predictable sounds in a sequence and altered mechanisms of continuous phase-alignment to expected sound onsets in aging. Given that deteriorations in these basic timing capacities may affect other higher-order cognitive processes (e.g., attention, perception, and action), these results underscore the need for future research examining the link between basic timing abilities and general cognition across the lifespan.HighligthsAging individuals (HO) show increased cortical excitability as compared to younger adults (HY);HO’s neural responses to fully predictable isochronous tones were larger and more variable than HY;HO showed reduced phase coherence in delta- and theta-band oscillations during listening to auditory sequence;Altogether, these results show altered sensory and timing processes in aging.
Root surface treatment for delayed replantation of avulsed teeth in animal models: a systematic review
Authors: Huaman Stephanie Díaz , Vilela Marina Moscardini , Nelson-Filho Paulo , De Rossi Andiara , de Queiroz Alexandra Mussolino , Paula-Silva Francisco Wanderley Garcia 
Published: March 2024

ABSTRACTThe aim of this study was to perform a systematic review of thein vivoeffectiveness of different types of root surface treatment materials used in delayed replanted teeth following tooth avulsion in animal models. A systematic review was conducted according to the PRISMA statement. Two reviewers performed a database search for studies published between January 1966 and April 2019 which were indexed in the PubMed, Scopus, and Bireme databases. Studies performedin vivo, in animal models with an avulsion/delayed replantation design (≥ 20 min of extra oral dry time) that evaluated the use of different materials for root surface treatment were included. The assessment for risk of bias was performed following recommendations included in Cochrane handbook for systematic reviews of interventions. We found 21 types of materials used for root surface treatment alone and 29 materials used with associations. Stannous fluoride, sodium fluoride, citric acid, doxycycline, Emdogain, alendronate, minocycline, Odanacatib, MFR buffer, recombinant human bone morphogenetic protein, gallium nitrate, acidulated phosphate fluoride, vitamin C, propolis, zoledronic acid, diode laser, indomethacin, fibrin sealant, adipose-tissue derived stem cells treatment and basic fibroblast growth gel. After Grading of Recommendations Assessment, Development, and Evaluation, four studies were scored as low quality of evidence, fifteen studies with moderate quality and six with high quality of evidence. Meta-analysis was not performed due to heterogeneity among studies and materials used for root surface treatment and therefore it was not possible to ascertain which material or protocol present better efficacy when used as root surface treatment material.
Fast volumetric fluorescence lifetime imaging of multicellular systems using single-objective light-sheet microscopy
Authors: Dunsing-Eichenauer Valentin , Hummert Johan , Chardès Claire , Schönau Thomas , Guignard Léo , Galland Rémi , Grenci Gianluca , Tillmann Max , Koberling Felix , Nock Corinna , Sibarita Jean-Baptiste , Viasnoff Virgile , Antolovic Ivan Michel , Erdmann Rainer , Lenne Pierre-François 
Published: March 2024

ABSTRACTFluorescence lifetime imaging (FLIM) is widely used for functional and multiplexed bioimaging, but is limited in speed, volumetric sampling of multicellular specimen, and live cell compatibility. To overcome these limitations, we have combined single objective light-sheet microscopy with pulsed excitation and time-resolved detection on a SPAD array detector. We report excellent quantitative agreement with confocal FLIM at 10-100-fold shorter acquisition times, down to 100 ms per image. We demonstrate lifetime-based multiplexing in 3D and time-lapse FLIM of mechanosensitive tension probes on living embryonic organoids, providing a powerful tool for functional imaging of dynamic multicellular systems.
Theta-Gamma Phase-Amplitude Coupling Supports Working Memory Performance in the Human Hippocampus
Authors: Salimpour Yousef , Anderson William S. 
Published: March 2024

AbstractPhase-amplitude coupling (PAC) occurs in the human hippocampus during working memory and supports the contribution of the hippocampus in the maintenance of multiple items. Additionally, PAC has the potential to reveal the neural mechanisms underlying multi-item maintenance in the hippocampus by providing a putative architecture for multi-item representation. Theta and gamma range rhythms are prominent neuronal oscillations in the hippocampus. Studies on the role of theta frequency oscillation in local field potentials in human memory have shown mixed evidence for successful remembering. The role of gamma oscillatory activity in contributing to memory retrieval is not yet fully understood. They also interact with each other in the form of PAC during memory performance. This study aims to investigate the neurophysiological function of theta-gamma PAC in the human hippocampus during a multi-item working memory task and characterize its association with performance. Theta-gamma cross-coupling investigation in the electrocorticographic signals was performed from the hippocampus recording of ten epilepsy patients while they were engaged with the working memory task. The results show strong correlations between PAC levels and the subjects memory performance, but no correlation with theta and gamma power individually, specifically in the retrieval phase of a working memory task. These observations demonstrate the possible role of PAC in memory-related operations, suggesting a PAC-based neural mechanism for working memory in the hippocampus.Significance StatementThe findings from this study elucidate the crucial role of phase-amplitude coupling in the human hippocampus during working memory tasks, specifically in the maintenance of multiple items. By analyzing electrocorticographic recordings from epilepsy patients engaged in a working memory task, our research unveils a direct correlation between PAC levels and memory performance during the retrieval phase, which is not observed when analyzing theta and gamma oscillations individually. These findings suggest a theta-gamma coupling based mechanism within the hippocampus that facilitates working memory, offering new insights into the complex neural processes underlying memory encoding and retrieval. This advancement in understanding the neural architecture of memory not only contributes to the foundational knowledge of cognitive neuroscience but also opens avenues for developing targeted interventions for enhancing memory performance with translational application in treating memory-related neurological disorders.
Enhancing amino acid productivity and profile in black soldier fly larvae through NAT transporter suppression in the excretion system
Authors: Liu Chia-Ming , Uehara Takuya , Shimoda Masami 
Published: March 2024

AbstractLarvae of the black soldier fly (Hermetia illucens, BSFL) are rich in valuable nutrients and offer a promising alternative protein source for animal feeds. Nonetheless, there is a pressing need to improve both the productivity and quality of BSFL proteins to ensure their viability, facilitating the industrial production. To fulfil the needs of different animals, it is necessary to adjust the profile of essential amino acids (AAs) in BSFL. Insects excrete surplus nutrients to maintain homeostasis; AAs are excreted by nutrient AA transporters (NATs) in the Malpighian tubules. We aimed to modify the composition of essential AAs by silencing the NAT in Malpighian tubules of BSFL (HiNATt). Silencing HiNATt resulted in a 56.2% decrease in body weight but a 77.3% increase in the total AA content. Notably, the contents of some valuable essential AAs were strongly increased (histidine, 156.8%; valine, 98.1%). These results suggest that inhibiting the function of HiNATt could modify the composition of accumulated AAs. This finding opens a new avenue for producing of BSFL with increased nutritional value as an alternative protein source.
Higher amplitudes of visual networks are associated with trait-but not state-depression
Authors: Zhang Wei , Dutt Rosie , Lew Daphne , Barch Deanna M. , Bijsterbosch Janine 
Published: March 2024

AbstractDespite depression being a leading cause of global disability, neuroimaging studies have struggled to identify replicable neural correlates of depression or explain limited variance. This challenge may, in part, stem from the intertwined state (current symptoms; variable) and trait (general propensity; stable) experiences of depression.Here, we sought to disentangle state from trait experiences of depression by leveraging a longitudinal cohort and stratifying individuals into four groups: those in remission (‘trait depression group’), those with large longitudinal severity changes in depression symptomatology (‘state depression group’), and their respective matched control groups (total analytic n=1,030). We hypothesized that spatial network organization would be linked to trait depression due to its temporal stability, whereas functional connectivity between networks would be more sensitive to state-dependent depression symptoms due to its capacity to fluctuate.We identified 15 large-scale probabilistic functional networks from resting-state fMRI data and performed group comparisons on the amplitude, connectivity, and spatial overlap between these networks, using matched control participants as reference. Our findings revealed higher amplitude in visual networks for the trait depression group at the time of remission, in contrast to controls. This observation may suggest altered visual processing in individuals predisposed to developing depression over time. No significant group differences were observed in any other network measures for the trait-control comparison, nor in any measures for the state-control comparison. These results underscore the overlooked contribution of visual networks to the psychopathology of depression and provide evidence for distinct neural correlates between state and trait experiences of depression.
Sexual dimorphism in the dorsal spot number and yellow surface in fire salamandersSalamandra salamandra ssp terrestrisLinnaeus, 1758 (Caudata: Salamandridae)
Authors: Bozon Martin , Marteau Basile 
Published: March 2024

AbstractSexual selection among amphibians is mainly based on size and colour dimorphism. Those criteria are less studied in salamanders. Only morphometric and yellow surface differences between males and females are known. We studied aSalamandra salamandra terrestrispopulation and observed significant differences in spots number and yellow surface area between males and females. Females have on average more spots and are blacker than males on their back.
Bisphosphonates synergistically enhance the antifungal activity of azoles in dermatophytes and other pathogenic molds
Authors: Kane Aidan , Rothwell Joanna G. , Guttentag Annabel , Hainsworth Steven , Carter Dee 
Published: March 2024

AbstractSuperficial infections of the skin, hair and nails by fungal dermatophytes are the most prevalent of human mycoses, and many infections are refractory to treatment. As current treatment options are limited, recent research has explored drug synergy with azoles for dermatophytoses. Bisphosphonates, which are approved to treat osteoporosis, can synergistically enhance the activity of azoles in diverse yeast pathogens but their activity has not been explored in dermatophytes or other molds. Market bisphosphonates risedronate, alendronate and zoledronate (ZOL) were evaluated for antifungal efficacy and synergy with three azole antifungals: fluconazole (FLC), itraconazole (ITR), and ketoconazole (KET). ZOL was the most active bisphosphonate tested, displaying moderate activity against nine dermatophyte species (MIC range 64–256 µg/mL), and was synergistic with KET in 88.9% of these species. ZOL was also able to synergistically improve the anti-biofilm activity of KET and combining KET and ZOL prevented the development of antifungal resistance. Rescue assays inTrichophyton rubrumrevealed that the inhibitory effects of ZOL alone and in combination with KET were due to the inhibition of squalene synthesis. Fluorescence microscopy using membrane- and ROS-sensitive probes demonstrated that ZOL and KET:ZOL compromised membrane structure and induced oxidative stress. Antifungal activity and synergy between bisphosphonates and azoles were also observed in other clinically relevant molds, including species ofAspergillusandMucor. These findings indicate that repurposing bisphosphonates as antifungals is a promising strategy for revitalising certain azoles as topical antifungals, and that this combination could be fast-tracked for investigation in clinical trials.ImportanceFungal infections of the skin hair and nails, generally grouped together as “tineas” are the most prevalent infectious disease globally. These infections, caused by fungal species known as dermatophytes, are generally superficial, but can in some cases become aggressive. They are also notoriously difficult to resolve, with few effective treatments and rising levels of drug resistance. Here we report a potential new treatment that combines azole antifungals with bisphosphonates. Bisphosphonates are approved for the treatment of low bone density diseases, and in fungi they inhibit the biosynthesis of the cell membrane, which is also the target of azoles. Combinations were synergistic across the dermatophyte species and prevented the development of resistance. We extended the study to molds that cause invasive disease, finding synergy in some problematic species. We suggest bisphosphonates could be repurposed as synergents for tinea treatment, and that this combination could be fast-tracked for use in clinical therapy.
Integrating Chromosome Conformation and DNA Repair in a Computational Framework to Assess Cell Radiosensitivity
Authors: Andriotty Matthew , Wang C.-K. Chris , Kapadia Anuj , McCord Rachel , Agasthya Greeshma 
Published: March 2024

ABSTRACTObjectiveThe arrangement of chromosomes in the cell nucleus has implications for cell radiosensitivity. The development of new tools to utilize Hi-C chromosome conformation data in nanoscale radiation track structure simulations allows forin silicoinvestigation of this phenomenon. We have developed a framework employing Hi-C-based cell nucleus models in Monte Carlo radiation simulations, in conjunction with mechanistic models of DNA repair, to predict not only the initial radiation-induced DNA damage, but also the repair outcomes resulting from this damage, allowing us to investigate the role chromosome conformation plays in the biological outcome of radiation exposure.ApproachIn this study, we used this framework to generate cell nucleus models based on Hi-C data from fibroblast and lymphoblastoid cells and explore the effects of cell type-specific chromosome structure on radiation response. The models were used to simulate external beam irradiation including DNA damage and subsequent DNA repair. The kinetics of the simulated DNA repair were compared with previous results.Main ResultsWe found that the fibroblast models resulted in a higher rate of inter-chromosome misrepair than the lymphoblastoid model, despite having similar amounts of initial DNA damage and total misrepairs for each irradiation scenario.SignificanceThis framework represents a step forward in radiobiological modeling and simulation allowing for more realistic investigation of radiosensitivity in different types of cells.