bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing generative replay for continual learning with long-term memory formation in the fruit fly
Authors: Robinson Brian S. , Joyce Justin , Norman-Tenazas Raphael , Vallabha Gautam K. , Johnson Erik C. 
Published: January 2023

AbstractContinual learning without catastrophic forgetting is a challenge for artificial systems but it is done naturally across a range of biological systems, including in insects. A recurrent circuit has been identified in the fruit fly mushroom body to consolidate long term memories (LTM), but there is not currently an algorithmic understanding of this LTM formation. We hypothesize that generative replay is occurring to consolidate memories in this recurrent circuit, and find anatomical evidence in synapse-level connectivity that supports this hypothesis. Next, we introduce a computational model which combines an initial experience phase and LTM phase to perform generative replay based continual learning. When evaluated on a CIFAR-100 class-incremental continual learning task, the modeled LTM phase increases classification performance by 20% and approaches within 2% of the performance for a non-incremental upper bound baseline. Unique elements of the proposed generative replay model include: 1) coupling high dimensional sparse activation patterns with generative replay and 2) sampling and reconstructing higher level representations for training generative replay (as opposed to reconstructing sensory-level or processed sensory-level representations). Additionally, we make the experimentally testable prediction that a specific set of synapses would need to undergo experience-dependent plasticity during LTM formation to support our generative replay based model.
“Tumor Treating Fields” delivered via electromagnetic induction have varied effects across glioma cell lines and electric field amplitudes
Authors: Ravin Rea , Cai Teddy X. , Li Aiguo , Briceno Nicole , Pursley Randall H. , Garmendia-Cedillos Marcial , Pohida Tom , Wang Herui , Zhuang Zhengping , Cui Jing , Morgan Nicole Y. , Williamson Nathan H. , Gilbert Mark R. , Basser Peter J. 
Published: January 2023

AbstractPrevious studies reported that alternating electric fields (EFs) in the intermediate frequency (100 – 300 kHz) and low intensity (1 – 3 V/cm) regime — termed “Tumor Treating Fields” (TTFields) — have a specific, anti-proliferative effect on glioblastoma multiforme (GBM) cells. However, the mechanism(s) of action remain(s) incompletely understood, hindering the clinical adoption of treatments based on TTFields. To advance the study of such treatmentin vitro, we developed an inductive device to deliver EFs to cell cultures which improves thermal and osmolar regulation compared to prior devices. Using this inductive device, we applied continuous, 200 kHz electromagnetic fields (EMFs) with a radial EF amplitude profile spanning 0 – 6.5 V/cm to cultures of primary rat astrocytes and several human GBM cell lines — U87, U118, GSC827, and GSC923 — for a duration of 72 hours. Cell density was assessed via segmented pixel densities from GFP expression (U87, U118) or from staining (astrocytes, GSC827, GSC923). Further RNA-Seq analyses were performed on GSC827 and GSC923 cells. Treated cultures of all cell lines exhibited little to no change in proliferation at lower EF amplitudes (0 – 3 V/cm). At higher amplitudes (> 4 V/cm), different effects were observed. Apparent cell densities increased (U87), decreased (GSC827, GSC923), or showed little change (U118, astrocytes). RNA-Seq analyses on treated and untreated GSC827 and GSC923 cells revealed differentially expressed gene sets of interest, such as those related to cell cycle control. Up- and down-regulation, however, was not consistent across cell lines nor EF amplitudes. Our results indicate no consistent, anti-proliferative effect of 200 kHz EMFs across GBM cell lines and thus contradict previousin vitrofindings. Rather, effects varied across different cell lines and EF amplitude regimes, highlighting the need to assess the effect(s) of TTFields and similar treatments on a per cell line basis.
Decoding single-cell multiomics: scMaui - A deep learning framework for uncovering cellular heterogeneity in presence of batch Effects and missing data
Authors: Jeong Yunhee , Ronen Jonathan , Kopp Wolfgang , Lutsik Pavlo , Akalin Altuna 
Published: January 2023

AbstractThe recent advances in high-throughput single-cell sequencing has significantly required computational models which can address the high complexity of single-cell multiomics data. Meticulous single-cell multiomics integration models are required to avoid biases towards a specific modality and overcome the sparsity. Batch effects obfuscating biological signals must also be taken into account. Here, we introduce a new single-cell multiomics integration model, Single-cell Multiomics Autoencoder Integration (scMaui) based on stacked variational encoders and adversarial learning. scMaui reduces the dimensionality of integrated data modalities to a latent space which outlines cellular heterogeneity. It can handle multiple batch effects independently accepting both discrete and continuous values, as well as provides varied reconstruction loss functions to cover various assays and preprocessing pipelines. We show that scMaui accomplishes superior performance in many tasks compared to other methods. Further downstream analyses also demonstrate its potential in identifying relations between assays and discovering hidden subpopulations.
A Clock and Wavefront Self-Organizing Model Recreates the Dynamics of Mouse Somitogenesis in-vivo and in-vitro
Authors: Klepstad Julie , Marcon Luciano 
Published: January 2023

AbstractDuring mouse development, presomitic mesoderm cells synchronize Wnt and Notch oscillations, creating sequential phase waves that pattern somites. Traditional somitogenesis models attribute phase waves to global signals that control the frequency of oscillations. However, increasing evidence suggests that they could arise in a self-organizing manner. Here, we introduce the Sevilletor, a novel reaction-diffusion system that serves as a framework to compare different somitogenesis patterning hypotheses. Using this framework, we propose the Clock and Wavefront Self-Organizing model, the first somitogenesis model that generates phase waves via local cell to cell communication independent of global frequency gradients. The model recapitulates the change in relative phase of Wnt and Notch observed during mouse somitogenesis and the formation of multiple phase waves observed upon ectopic expansion of posterior signals. Moreover, it provides a theoretical basis for understanding the excitability of mouse presomitic mesoderm cells observed in vitro.
Super-enhancer driven expression of BAHCC1 promotes melanoma cell proliferation and genome stability
Authors: Berico Pietro , Nogaret Maguelone , Gambi Giovanni , Davidson Guillaume , Cigrang Max , Vokshi Bujamin H , Le Gras Stephanie , Mengus Gabrielle , Ye Tao , Dalmasso Mélanie , Compe Emmanuel , Bertolotto Corine , Davidson Irwin , Coin Frédéric 
Published: January 2023

AbstractSuper enhancers (SE) are stretches of active enhancers ensuring high expression levels of key genes associated with cell function and survival. The identification of cancer-specific SE-driven genes and their functional characterization may prove to be a powerful means for the development of innovative therapeutic strategies. By performing epigenomic profiling in patient-derived short-term melanoma cultures, we identify a SE promoting the specific expression of BAHCC1 in a broad panel of cutaneous and uveal melanoma cells. BAHCC1 is highly expressed in metastatic melanoma, correlates with decreased patient survival and is required for tumor growth. Integrative genomics analyses reveal that BAHCC1 is a transcriptional regulator controlling expression of a subset of E2F/KLF-dependent cell cycle and DNA repair genes. BAHCC1 associates with BRG1-containing remodeling complexes at the promoters of these genes. In agreement, BAHCC1 silencing leads to decreased cell proliferation and delay in DNA repair. Consequently, BAHCC1 deficiency cooperates with PARP inhibition to induce melanoma cell death. Our study identifies a novel SE-driven gene expressed in cutaneous and uveal melanoma and demonstrates how its inhibition can be exploited as a therapeutic target, alone or in combination with DNA damage-inducing agents.
A 3-dimensional molecular cartography of human cerebral organoids revealed by double-barcoded spatial transcriptomics
Authors: Lozachmeur Gwendoline , Bramoulle Aude , Aubert Antoine , Stüder François , Moehlin Julien , Madrange Lucie , Yates Frank , Deslys Jean-Philippe , Mendoza-Parra Marco Antonio 
Published: January 2023

AbstractSpatially-resolved transcriptomics is revolutionizing our understanding of complex tissues, but their current use for the exploration of a few sections is not representative of their 3-dimensional architecture. In this work we present a low-cost strategy for manufacturing molecularly double-barcoded DNA arrays, enabling large-scale spatially-resolved transcriptomics studies. We applied this technique to spatially resolve gene expression in several human brain organoids, including the reconstruction of a 3-dimensional view from multiple consecutive sections, revealing gene expression divergencies throughout the tissue.
Comparative phylogeography of Ponto-Caspian amphipods throughout the invaded Baltic and native NW Black Sea donor ranges – can introduction mode affect genetic diversity?
Authors: Copilaș-Ciocianu Denis , Šidagytė-Copilas Eglė , Son Mikhail O. , Morhun Halyna , Macher Jan Niklas , Arbačiauskas Kęstutis 
Published: January 2023

AbstractThe Baltic countries harbor a diverse assemblage of alien amphipods of Ponto-Caspian origin. The composition of this fauna was shaped by three invasion waves: 1) pre-20thcentury dispersals via watershed-connecting canals, 2) deliberate introductions in the 1960s, and 3) new dispersals during the last decade via shipping and pre-existing canals. Given this rich invasion history, we test whether genetic diversity (mitochondrial and nuclear) differs between the native and invaded ranges and between the deliberately introduced species and the ones that dispersed on their own. Our results show a significant decrease in mitochondrial but not nuclear genetic diversity in the invaded Baltic range. We also find that in the invaded range the introduced species exhibit a higher mitochondrial and nuclear genetic diversity than the species that dispersed on their own, while in the native range only the nuclear diversity is higher in introduced species. Mitochondrial diversity was more structured geographically in the native range and the dominant invasive haplotypes were detected in the native populations of all but one species, further highlighting the utility of this marker in tracing invasion sources. Our comparative approach provides important insight into the inter-range genetic diversity of Ponto-Caspian invaders, highlighting the role of introduction mode.
Rodent ultrasonic vocal interaction resolved with millimeter precision using hybrid beamforming
Authors: Sterling M. L. , Englitz B. 
Published: January 2023

AbstractUltrasonic vocalizations (USVs) fulfill an important role in communication and navigation in many species. Because of their social and affective significance, rodent USVs are increasingly used as a behavioral measure in neurodevelopmental and neurolinguistic research. Reliably attributing USVs to their emitter during close interactions has emerged as a difficult, key challenge. If addressed, all subsequent analyses gain substantial confidence.We present a hybrid ultrasonic tracking system, HyVL, that synergistically integrates a high-resolution acoustic camera with high-quality ultrasonic microphones. HyVL is the first to achieve millimeter precision (~3.4-4.8mm, 91% assigned) in localizing USVs, ~3x better than other systems, approaching the physical limits (mouse snout ~ 10mm).We analyze mouse courtship interactions and demonstrate that males and females vocalize in starkly different relative spatial positions, and that the fraction of female vocalizations has likely been overestimated previously due to imprecise localization. Further, we find that male mice vocalize more intensely when interacting with two mice, an effect mostly driven by the dominant male.HyVL substantially improves the precision with which social communication between rodents can be studied. It is also affordable, open-source, easy to set up, can be integrated with existing setups, and reduces the required number of experiments and animals.Data & Code AvailabilityDuring the review process, reviewers can access all Data and Code via the link below:https://data.donders.ru.nl/loqin/reviewer-208072048/iJ4c-oRNlPIp3vArKiYQ0lAW9FipiHL8foxSzwt1FDAUponacceptance, these materials will be made available to the public.
A mathematical model for axonal transport of large cargo vesicles
Authors: Rahman Nizhum , Oelz Dietmar B. 
Published: January 2023

AbstractIn this study, we consider axonal transport of large cargo vesicles characterised by transient expansion of the axon shaft. Our goal is to formulate a mathematical model which captures the dynamic mechanical interaction of such cargo vesicles with the membrane associated periodic cytoskeletal structure (MPS). It consists of regularly spaced actin rings that are transversal to the longitudinal direction of the axon and involved in the radial contraction of the axon. A system of force balance equations is formulated by which we describe the transversal rings as visco-elastic Kelvin-Voigt elements. In a homogenisation limit, we reformulate the model as a free boundary problem for the interaction of the submembranous MPS with the large vesicle. We derive a non-linear force-velocity relation as a quasi-steady state solution. Computationally we analyse the vesicle size dependence of the transport speed and use an asymptotic approximation to formulate it as a power law that can be tested experimentally.
Recurrent phases of strict protein limitation inhibit tumor growth and restore lifespan in aDrosophilaintestinal cancer model
Authors: Pfefferkorn Roxana M. , Mortzfeld Benedikt M. , Fink Christine , von Frieling Jakob , Bossen Judith , Esser Daniela , Kaleta Christoph , Rosenstiel Philip , Heine Holger , Roeder Thomas 
Published: January 2023

AbstractDiets that restrict caloric or protein intake offer a variety of benefits, including decreasing the incidence of cancer. However, whether such diets pose a substantial therapeutic benefit as auxiliary cancer treatments remains unclear. We determined the effects of severe protein depletion on tumorigenesis in aDrosophila melanogasterintestinal tumor model, using a human RAF gain-of-function allele. Severe and continuous protein restriction significantly reduced tumor growth but resulted in premature death. Therefore, we developed a diet in which short periods of severe protein restriction alternated cyclically with periods of complete feeding. This nutritional regime reduced tumor mass, restored gut functionality, and normalized the lifespan of oncogene-expressing flies to the levels observed in healthy control flies. Furthermore, this diet reduced the chemotherapy-induced stem cell activity associated with tumor recurrence. Transcriptome analysis revealed long-lasting changes in the expression of key genes involved in multiple major developmental signaling pathways. Overall, the data suggest that recurrent severe protein depletion effectively mimics the health benefits of continuous protein restriction, without undesired nutritional shortcomings. This provides seminal insights into the mechanisms of the transcriptomic memory effect required to maintain the positive effects of protein restriction throughout the phases of a full diet.
Nanovirseq: dsRNA sequencing for plant virus and viroid detection by Nanopore sequencing
Authors: Javaran Vahid J. , Poursalavati Abdonaser , Lemoyne Pierre , Ste-Croix Dave T. , Moffett Petter , Fall Mamadou L. 
Published: January 2023

AbstractWorldwide, there is a need for certified clean plant materials to limit viral diseases spread. In order to design a robust and proactive viral-like disease certification, diagnostics, and management program, it is essential to have a fast, inexpensive, and user-friendly tool. The purpose of this study was to determine whether dsRNA-based nanopore sequencing can be a reliable method for the detection of viruses and viroids in grapevines or not. Compared to direct RNA sequencing from rRNA-depleted total RNA (rdTotalRNA), direct-cDNA sequencing from dsRNA (dsRNAcD) yielded more viral reads and detected all grapevine viruses and viroids detected using Illumina MiSeq sequencing (dsRNA-MiSeq). With dsRNAcD sequencing it was possible to detect low abundance viruses (e.g., Grapevine red globe virus) where rdTotalRNA sequencing failed to detect them. Indeed, even after removing rRNA, rdTotalRNA sequencing yielded low viral read numbers. rdTotalRNA sequencing was not sensitive enough to detect all the viruses detected by dsRNA-MiSeq. In addition, there was a false positive identification of a viroid in the rdTotalRNA sequencing that was due to misannotation of a host-driven read. For quick and accurate reads classification, two different taxonomical classification workflows based on protein and nucleotide homology were evaluated in this study, namely DIAMOND&MEGAND (DIA&MEG) and Centrifuge&Recentrifuge (Cent&Rec), respectively. Virome profiles from both workflows were similar except for grapevine endophyte endornavirus (GEEV), which was only detected using DIA&MEG. However, because DIA&MEG’s classification is based on protein homology, it cannot detect viroid infection despite giving more robust results. Even though Cent&Rec’s virus and viroid detection workflow was faster (30 minutes) than DIA&MEG’s (two hours), it could not provide the details and information DIA&MEG was able to provide. As demonstrated in our study, nanopore dsRNAcD sequencing and the proposed data analysis workflows are suitable and reliable for viruses and viroids detection, especially in grapevine where viral mixed infection is common.
Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation
Authors: Vanrobeys Yann , Mukherjee Utsav , Langmack Lucy , Bahl Ethan , Lin Li-Chun , Michaelson Jacob J , Abel Ted , Chatterjee Snehajyoti 
Published: January 2023

AbstractMemory consolidation involves discrete patterns of transcriptional events in the hippocampus. Despite the emergence of single-cell transcriptomic profiling techniques, defining learning-responsive gene expression across subregions of the hippocampus has remained challenging. Here, we utilized unbiased spatial sequencing to elucidate transcriptome-wide changes in gene expression in the hippocampus following learning, enabling us to define molecular signatures unique to each hippocampal subregion. We find that each subregion of the hippocampus exhibits distinct yet overlapping transcriptomic signatures. Although the CA1 region exhibited increased expression of genes related to transcriptional regulation, the DG showed upregulation of genes associated with protein folding. We demonstrate the functional relevance of subregion-specific gene expression by genetic manipulation of a transcription factor selectively in the CA1 hippocampal subregion, leading to long-term memory deficits. This work demonstrates the power of using spatial molecular approaches to reveal transcriptional events during memory consolidation.
sLASER and PRESS Perform Similarly at Revealing Metabolite-Age Correlations
Authors: Hui Steve C.N. , Gong Tao , Zöllner Helge J. , Hupfeld Kathleen E. , Gudmundson Aaron T. , Murali-Manohar Saipavitra , Davies-Jenkins Christopher W. , Song Yulu , Chen Yufan , Oeltzschner Georg , Wang Guangbin , Edden Richard A. E. 
Published: January 2023

AbstractPurposeTo compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate.MethodsMRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale (CSO) and posterior cingulate cortex (PCC) regions. Acquisition parameters included TR/TE 2000/30 ms; 96 transients; 2048 datapoints sampled at 2 kHz.Spectra were analyzed using Osprey. Signal-to-noise ratio (SNR), full-width-half-maximum linewidth of tCr, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement.ResultsSNR and linewidth were significantly higher (p<0.05) for sLASER than PRESS. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. Metabolite measures were significantly correlated (p<0.05) for most metabolites between the two methods except GABA, Gln and Lac in CSO and GSH, Lac and NAAG in PCC. Metabolite-age relationships were consistently identified using both PRESS and sLASER. Similar CVs were observed for most metabolites.ConclusionThe study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in CSO and PCC data acquired at 3T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in ‘good’ brain regions at clinical field strength.
A single dietary factor, daily consumption of a fermented beverage, can modulate the gut microbiome within the same ethnic community
Authors: Das Santanu , Özkurt Ezgi , Joishy Tulsi Kumari , Deb Dibyayan , Mukherjee Ashis K. , Hildebrand Falk , Khan Mojibur R. 
Published: January 2023

AbstractIn this study, the impact of traditional rice-based fermented alcoholic beverages (Apong) on the gut microbiome and health of theMishingcommunity in India was examined. Two groups that consumed one of these beverages were compared to a control group that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed thatApongdrinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice ofApong, withApongdrinkers having a more diverse and distinct microbiome compared to non-drinkers.Apongdrink type or being a non-drinker explained even a higher variation of fecal metabolome composition than microbiome composition andApongdrinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in maintaining gut health.