bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-stimulus alpha oscillations encode stimulus-specific visual predictions
Authors: Hetenyi Dorottya , Haarsma Joost , Kok Peter 
Published: March 2024

AbstractPredictions of future events have a major impact on how we process sensory signals. However, it remains unclear how the brain keeps predictions online in anticipation of future inputs. Here, we combined magnetoencephalography (MEG) and multivariate decoding techniques to investigate the content of perceptual predictions and their frequency characteristics. Participants were engaged in a shape discrimination task, while auditory cues predicted which specific shape would likely appear. Frequency analysis revealed significant oscillatory fluctuations of predicted shape representations in the pre-stimulus window in the alpha band (10 – 11Hz). Furthermore, we found that this stimulus-specific alpha power was linked to expectation effects on shape discrimination. Our findings demonstrate that sensory predictions are embedded in pre-stimulus alpha oscillations and modulate subsequent perceptual performance, providing a neural mechanism through which the brain deploys perceptual predictions.
Increased perceptual reliability reduces membrane potential variability in cortical neurons
Authors: von Hünerbein Ben , Jordan Jakob , Lohuis Matthijs Oude , Marchesi Pietro , Olcese Umberto , Pennartz Cyriel M.A. , Senn Walter , Petrovici Mihai A. 
Published: March 2024

AbstractUncertainty is omnipresent. While humans and other animals take uncertainty into account during decision making, it remains unclear how it is represented in cortex. To investigate the effect of stimulus reliability on uncertainty representation in cortical neurons, we analyzed single unit activity data recorded in mouse PPC, while animals performed a multisensory change detection task. We further used simulation-based inference (SBI) to infer membrane potential statistics underlying the spiking activity. Our analysis shows that stimulus changes increase spiking rate while decreasing its variability. The inferred membrane potential statistics suggest that PPC neurons decrease their membrane potential variability in response to task relevant stimuli. Furthermore, more perceptually reliable stimuli lead to a larger decrease in membrane potential variability than less reliable ones. These findings suggest that individual cortical neurons track uncertainty, providing Bayesian benefits for downstream computations.
Evolution of Virulence in Emerging Epidemics: From Theory to Experimental Evolution and Back
Authors: Benhamou Wakinyan , Blanquart François , Choisy Marc , Berngruber Thomas W. , Choquet Rémi , Gandon Sylvain 
Published: March 2024

AbstractThe experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage λ spreading in continuous cultures ofEscherichia coli. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis – including calculations of the selection gradients – and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage λ. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.
Assessing tooth wear progression in primates: A longitudinal study using intraoral scanning technology
Authors: Towle Ian , Krueger Kristin L. , Hernando Raquel , Hlusko Leslea J. 
Published: March 2024

AbstractIntraoral scanners are widely used in a clinical setting for orthodontic treatments and tooth restorations, and are also useful for assessing dental wear and pathology progression. In this study, we assess the utility of using an intraoral scanner and associated software for quantifying dental tissue loss in non-human primates. An upper and lower second molar for 31 captive hamadryas baboons (Papio hamadryas) were assessed for dental tissue loss progression over multiple years (n= 62 teeth). The animals are part of the Southwest National Primate Research Center and were all fed the same monkey-chow diet over their lifetimes. Two molds of each dentition were taken at either two- or three-year intervals, and the associated casts scanned using an intraoral scanner (Medit i700). Tissue loss was calculated inWearCompareby superimposition of the two scans followed by subtraction analysis. Four individuals had dental caries, and were assessed separately. The results demonstrate the reliability of these techniques in capturing tissue loss data, evidenced by the alignment consistency between scans, lack of erroneous tissue gain between scans, and uniformity of tissue loss patterns among individuals (e.g., functional cusps showing the highest degree of wear). The average loss per mm² per year for all samples combined was 0.05 mm³ (0.04 mm³ for females and 0.08 mm³ for males). There was no significant difference in wear progression between upper and lower molars. Substantial variation in the amount of tissue loss among individuals was found, despite their uniform diet. These findings foster multiple avenues for future research, including the exploration of wear progression across dental crowns and arcades, correlation between different types of tissue loss (e.g., attrition, erosion, fractures, caries), interplay between tissue loss and microwear/topographic analysis, and the genetic underpinnings of tissue loss variation.
Versatile roles of protein flavinylation in bacterial extracyotosolic electron transfer
Authors: Huang Shuo , Méheust Raphaël , Barquera Blanca , Light Samuel H. 
Published: March 2024

ABSTRACTBacteria perform diverse redox chemistries in the periplasm, cell wall, and extracellular space. Electron transfer for these extracytosolic activities is frequently mediated by proteins with covalently bound flavins, which are attached through post-translational flavinylation by the enzyme ApbE. Despite the significance of protein flavinylation to bacterial physiology, the basis and function of this modification remains unresolved. Here we apply genomic context analyses, computational structural biology, and biochemical studies to address the role of ApbE flavinylation throughout bacterial life. We find that ApbE flavinylation sites exhibit substantial structural heterogeneity. We identify two novel classes of flavinylation substrates that are related to characterized proteins with non-covalently bound flavins, providing evidence that protein flavinylation can evolve from a non-covalent flavoprotein precursor. We further find a group of structurally related flavinylation-associated cytochromes, including those with the domain of unknown function DUF4405, that presumably mediate electron transfer in the cytoplasmic membrane. DUF4405 homologs are widespread in bacteria and related to ferrosome iron storage organelle proteins that may facilitate iron redox cycling within ferrosomes. These studies reveal a complex basis for flavinylated electron transfer and highlight the discovery power of coupling comparative genomic analyses with high-quality structural models.
Hallucination- and delusion-like experiences are associated with increased precision of sensory evidence in perceptual inference
Authors: Scaramozzino Francesco , McKay Ryan , Furl Nicholas 
Published: March 2024

AbstractBACKGROUND AND HYPOTHESISPredictive coding proposes that psychotic phenomenology stems from alterations in precision encoding of neural signals. Previous studies indicate links between psychotic-like experiences, increased sensory evidence precision, and reduced data-gathering in probabilistic reasoning. If sensory precison is increased in bottom-up signalling, we would expect it to be present in perceptual inference. Here, we investigated whether increased sensory precision and reduced data-gathering relate to subclinical psychotic-like experiences in perceptual inference.STUDY DESIGNWe fitted drift-diffusion models to performance on the Random Dot Motion task (RDM) of 191 participants from the general population. Drift rate (a proxy for precision of sensory evidence) and decision threshold parameters could vary: 1) between groups with higher vs. lower levels of psychotic phenotypes; 2) as dependent variables in a regression model having psychotic phenotypes as predictors. Using the beads task, we also attempted to replicate the finding that reduced data-gathering is associated with delusional ideation.STUDY RESULTSBoth delusion- and hallucination-like experiences were associated with higher precision of sensory evidence (higher drift rates) in RDM. Hallucination-like experiences were also associated with lower decision thresholds. In probabilistic reasoning, we did not find reduced data-gathering associated with any psychotic-like experiences.CONCLUSIONSOur findings suggest that psychotic-like experiences are associated with increased precision of sensory evidence when discriminating motion direction. A higher hallucinatory phenotype was also linked to reduced gathering of information. These specificities of information processing might represent underlying decision-making mechanisms contributing to the formation of psychotic phenomenology in the general population.
A RAG Chatbot for Precision Medicine of Multiple Myeloma
Authors: Quidwai Mujahid Ali , Lagana Alessandro 
Published: March 2024

AbstractThe advent of precision medicine has revolutionized cancer treatment by integrating individual genetic, lifestyle, and environmental factors to tailor patient care (Huang et al., 2020; Ginsburg and Phillips, 2018). However, the complexity and heterogeneity of diseases like Multiple Myeloma (MM) pose significant challenges in leveraging the vast amounts of genomic data and biomedical literature available for personalized treatment planning (Rajkumar, 2014; Röllig et al., 2015). To address this, we present an innovative Retrieval-Augmented Generation (RAG) based chatbot framework that harnesses the power of Natural Language Processing (NLP) and state-of-the-art language models to curate and analyze MM-specific literature and provide personalized treatment recommendations based on patient-specific genomic data (Lewis et al., 2020).Our framework integrates the BioMed-RoBERTa-base model for embedding generation (Gururangan et al., 2020) and the Mistral-7B language model for question answering (Anthropic, 2023), enabling effective understanding and response to complex clinical queries. The retrieval component is enhanced by Amazon OpenSearch Service, ensuring fast and accurate access to relevant information. A comprehensive data analysis pipeline, including exploratory data analysis, semantic search, clustering, and topic modeling, provides valuable insights into the MM research landscape, informing the chatbot’s knowledge base and uncovering potential research directions (Blei et al., 2003; Mikolov et al., 2013).Deployed using Amazon Kendra, our RAG chatbot offers a user-friendly and scalable platform for accessing MM information, incorporating features such as user authentication, customizable web interface, and continuous improvement based on user feedback. The framework aims to democratize access to precision medicine by providing clinicians with a sophisticated tool for interpreting complex genomic data in the context of MM, streamlining clinical workflows, and facilitating the development of personalized treatment plans (Patel et al., 2015).This paper presents the conceptualization, development, and potential impact of our RAG-based chatbot framework on the landscape of MM treatment and precision medicine. We argue that the synergistic integration of AI, NLP, and domain-specific knowledge marks a new era of healthcare, characterized by highly personalized, data-driven, and effective treatment modalities (Thong et al., 2021). Our framework not only advances the field of precision medicine in MM but also serves as a blueprint for the development of similar systems in other complex diseases, ultimately improving patient outcomes and quality of life.
Assessing horizontal gene transfer in the rhizosphere ofBrachypodium distachyonusing fabricated ecosystems (EcoFABs)
Authors: Priya Shweta , Rossbach Silvia , Eng Thomas , Lin Hsiao-Han , Andeer Peter F. , Mortimer Jenny C. , Northen Trent R. , Mukhopadhyay Aindrila 
Published: March 2024

AbstractHorizontal gene transfer (HGT) is a major process by which genes are transferred within microbes in the rhizosphere. However, examining HGT remains challenging due to the complexity of mimicking conditions within the rhizosphere. Fabricated ecosystems (EcoFABs) have been used to investigate several complex processes in plant associated environments. Here we show that EcoFABs are efficient tools to examine and measure HGT frequency in the rhizosphere. We provided the first demonstration of gene transfer via triparental conjugation system in theBrachypodium distachyonrhizosphere in the EcoFABs usingPseudomonas putidaKT2440 as both donor and recipient bacterial strain with the donor having the mobilizable and non-self-transmissible plasmid. We also observed that the frequency of conjugal plasmid transfer in the rhizosphere is potentially dependent on the plant developmental stage, and composition and amount of root exudates. The frequency of conjugation also increased with higher numbers of donor cells. We have also shown the transfer of plasmid fromP. putidato anotherB. distachyonroot colonizer,Burkholderiasp. showing the possibility of HGT within a rhizosphere microbial community. Environmental stresses also influence the rate of HGT in the rhizosphere between species and genera. Additionally, we observed transfer of a non-self transmissible donor plasmid without the helper strain on agar plates when supplemented with environmental stressors, indicating reduced dependency on the helper plasmid under certain conditions. This study provides a robust workflow to evaluate conjugal transfer of engineered plasmids in the rhizosphere when such plasmids are introduced in a field or plant associated environment.ImportanceWe report the use of EcoFABs to investigate the HGT process in a rhizosphere environment. It highlights the potential of EcoFABs in recapitulating the dynamic rhizosphere conditions as well as their versatility in studying plant-microbial interactions. This study also emphasizes the importance of studying the parameters impacting the HGT frequency. Several factors such as plant developmental stages, nutrient conditions, number of donor cells and environmental stresses influence gene transfer within the rhizosphere microbial community. This study paves the way for future investigations into understanding the fate and movement of engineered plasmids in a field environment.
PRMT5 is required for full-lengthHTTexpression by repressing multiple proximal intronic polyadenylation sites
Authors: AlQazzaz Mona A. , Ciamponi Felipe E. , Ho Jolene C. , Maron Maxim I. , Yadav Manisha , Sababi Aiden M. , MacLeod Graham , Ahmadi Moloud , Bullivant Garrett , Tano Vincent , Langley Sarah R. , Sánchez-Osuna María , Sachamitr Patty , Kushida Michelle , Richards Laura , Bardile Costanza Ferrari , Pouladi Mahmoud A. , Pugh Trevor , Tyers Mike , Angers Stephane , Dirks Peter B. , Bader Gary D. , Massirer Katlin B. , Barsyte-Lovejoy Dalia , Shechter David , Harding Rachel J. , Arrowsmith Cheryl H. , Prinos Panagiotis 
Published: March 2024

AbstractExpansion of the CAG trinucleotide repeat tract in exon 1 of theHuntingtin(HTT) gene above a threshold of ∼36 repeats causes Huntington’s disease (HD) through the expression of a polyglutamine-expanded form of the HTT protein. This mutation triggers wide-ranging cellular and biochemical pathologies leading to cognitive, motor, and psychiatric symptoms in HD patients. As accurate splicing is required to produce the full-length HTT protein of ∼348 kDa, targetingHTTsplicing with small molecule drugs is a compelling approach to lower HTT protein levels to treat HD, and splice modulators are being tested in the clinic. Here, we identify PRMT5 as a novel regulator ofHTTmRNA splicing and alternative polyadenylation. PRMT5 inhibition disrupts the splicing ofHTTintrons 9 and 10, leading to activation of multiple proximal intronic polyadenylation sites within these introns and promoting premature termination, cleavage and polyadenylation (PCPA) of theHTTmRNA, thus lowering total HTT protein levels. We also detected increasing levels of these truncated, intron-containingHTTtranscripts across a series of neuronal differentiation samples which correlated with lower PRMT5 expression. Notably, PRMT5 inhibition in glioblastoma (GBM) stem cells potently induced neuronal differentiation. We posit that PRMT5-mediated regulation of intronic polyadenylation, premature termination and cleavage of theHTTmRNA modulates HTT expression and plays an important role during embryonic development and neuronal differentiation.
Experimental evolution of an RNA virus inCaenorhabditis elegans
Authors: Castiglioni Victoria G. , Olmo-Uceda María J. , Martín Susana , Félix Marie-Anne , González Rubén , Elena Santiago F. 
Published: March 2024

ABSTRACTThe discovery of Orsay virus (OrV), the first virus infecting wild populations ofCaenorhabditis elegans, has boosted studies of viral immunity pathways in this nematode. Considering the many advantages thatC. elegansoffers for fundamental research in host-pathogen interactions, this pathosystem has high potential to become a model system for experimental virus evolution studies. However, the evolutionary constraints operating in this pathosystem have barely been explored. Here we describe for the first time an evolution experiment of two different OrV strains inC. elegans. After 10 serial passages of evolution, we report slight changes in infectivity and non-synonymous mutations fixed in the evolved viral populations. In addition, we observed numerous minor variants emerging in the viral population. These minor variants were not randomly distributed along the genome but concentrated in polymorphic genomic regions. Overall, our work established the grounds for future experimental virus evolution studies usingCaenorhabditisnematodes.HIGHLIGHTSCaenorhabditis elegans-Orsay virus is a convenient pathosystem to study virus evolution.The approach used to test the viral strains may interfere with the infection phenotypes observed.There may be specific genomic hotspots regions of nucleotide diversity important for the evolution of Orsay virus.The substitution rate observed for Orsay virus was low, suggesting that the two strains studied might be already well adapted to laboratory conditions.
FTO-mediated m6A demethylation of ULK1 mRNA promotes autophagy and activation of hepatic stellate cells in liver fibrosis
Authors: Huang Tingjuan , Zhang Chunhong , Ren Junjie , Shuai Qizhi , Li Xiaonan , Li Xuewei , Xie Jun , Xu Jun 
Published: March 2024

AbstractThe activation of hepatic stellate cells (HSCs) is the central link in the occurrence and development of liver fibrosis. Our previous studies showed that autophagy promotes HSCs activation and ultimately accelerates liver fibrosis. Unc-51-like autophagy activating kinase 1 (ULK1) is an autophagic initiator in mammals and N6-methyladenosine (m6A) modification is closely related to autophagy. In this study, we find that m6A demethylase fat mass and obesity-associated protein (FTO) is upregulated during HSCs activation and bile duct ligation (BDL)-induced hepatic fibrosis, which is the m6A methylase with the most significant difference in expression. Importantly, we identify that FTO overexpression aggravates HSCs activation and hepatic fibrosis via autophagy. Mechanistically, compared with other autophagy-related genes, ULK1 is the target of FTO due to FTO mainly mediates the m6A demethylation of ULK1 and upregulates its expression, thereby enhancing autophagy and activation of HSCs. Noteworthy, m6A reader YTH domain-containing protein 2 (YTHDC2) decreases ULK1 mRNA level via recognizing the m6A binding site and ultimately inhibits autophagy and activation of HSCs. Taken together, our findings highlight m6A-dependent ULK1 as an essential regulator of HSCs autophagy and reveal ULK1 as a novel potential therapeutic target for hepatic fibrosis treatment.Graphical Abstractm6A demethylases FTO promoted autophagy via recognizing the ULK1 m6A binding site, thus triggering HSCs activation, and eventually leading to liver fibrosis. In this process, YTHDC2 participated in the translation of ULK1.
5-HT1B receptors mediate dopaminergic inhibition of vesicular fusion and GABA release from striatonigral synapses
Authors: Molinari Maya , Lieberman Ori J. , Sulzer David , Santini Emanuela , Borgkvist Anders 
Published: March 2024

AbstractThe substantia nigra pars reticulata (SNr), a crucial basal ganglia output nucleus, contains a dense expression of dopamine D1 receptors (D1Rs), along with dendrites belonging to dopaminergic neurons of substantia nigra pars compacta. These D1Rs are primarily located on the terminals of striatonigral medium spiny neurons, suggesting their involvement in the regulation of neurotransmitter release from the direct pathway in response to somatodendritic dopamine release. To explore the hypothesis that D1Rs modulate GABA release from striatonigral synapses, we conducted optical recordings of striatonigral activity and postsynaptic patch-clamp recordings from SNr neurons in the presence of dopamine and D1R agonists. We found that dopamine inhibits optogenetically triggered striatonigral GABA release by modulating vesicle fusion and Ca2+influx in striatonigral boutons. Notably, the effect of DA was independent of D1R activity but required activation of 5-HT1B receptors. Our results suggest a serotonergic mechanism involved in the therapeutic actions of dopaminergic medications for Parkinson’s disease and psychostimulant-related disorders.