bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring mate choice and male strategies in a polymorphic moth
Authors: Selenius Eetu , De Pasqual Chiara , Hänninen Matleena , Kartano Liisa , Winters Sandra , Mappes Johanna 
Published: August 2024

AbstractColor polymorphisms in natural populations often reflect the interplay between various selective pressures, such as natural and sexual selection. In this study, we investigate the dynamics of sexual selection operating on color polymorphism in wood tiger moths under different ecological contexts. Wood tiger moths exhibit polymorphism in male hindwing coloration, with individuals possessing one or two dominant W alleles displaying two forms of white coloration that differ in their UV reflectance (WW, Wy), while those with two recessive y alleles exhibit yellow coloration (yy). Females carry the color alleles, but do not express them phenotypically. We performed two mate choice experiments that simulated two ecological conditions: one with limited morph availability and low male encounter rates and the other with all morphs present and high potential for male encounters. We demonstrate that WW males consistently experience higher mating success compared to yy males, irrespective of the presence of Wy males and male encounter rates. Surprisingly, mating with a WW male does not confer direct reproductive benefits to females in terms of lifetime reproductive success; instead, Wy females exhibit overall higher reproductive success regardless of their mating partner. Although the precise mechanism driving the higher mating success of WW males remains unclear, a temporal decline in mating success of WW males suggests potential differences in male mating strategies. Our findings support the hypothesis that sexual selection contributes to the maintenance of polymorphism, revealing a stable mating advantage of a particular color morph that may be offset by other selective forces.
Flexible modeling of large-scale neural network stimulation: electrical and optical extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX)
Authors: Pierce Anne F. , Shupe Larry , Fetz Eberhard , Yazdan-Shahmorad Azadeh 
Published: August 2024

AbstractBackgroundComputational models that predict effects of neural stimulation can be used as a preliminary tool to informin-vivoresearch, reducing the costs, time, and ethical considerations involved. However, current models do not support the diverse neural stimulation techniques usedin-vivo, including the expanding selection of electrodes, stimulation modalities, and stimulation paradigms.New MethodTo develop a more comprehensive software, we created several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool from Newcastle University. VERTEX simulates input currents in a large population of multi-compartment neurons within a small cortical slice to model electric field stimulation, while recording local field potentials (LFPs) and spiking activity. Our extensions to its existing electric field stimulation framework include allowing multiple pairs of parametrically defined electrodes and biphasic, bipolar stimulation delivered at programmable delays. To support the growing use of optogenetic approaches for targeted neural stimulation, we introduced a feature that models optogenetic stimulation through an additional VERTEX input function that converts irradiance to currents at optogenetically responsive neurons. Finally, we added extensions to allow complex stimulation protocols including paired-pulse, spatiotemporal patterned, and closed-loop stimulation.ResultsWe demonstrated our novel features using VERTEX’s built-in functionalities, with results in alignment with other models and experimental work.ConclusionsOur extensions provide an all in one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.
GPT-4V shows human-like social perceptual capabilities at phenomenological and neural levels
Authors: Santavirta Severi , Wu Yuhang , Nummenmaa Lauri 
Published: August 2024

AbstractHumans navigate the social world by rapidly perceiving social features from other people and their interaction. Recently, large-language models (LLMs) have achieved high-level visual capabilities for detailed object and scene content recognition and description. This raises the question whether LLMs can perceive nuanced and tacit social information form images and videos, and whether the high-dimensional perceptual structure aligns with that of humans. We collected social perceptual evaluations for 138 social features from GPT-4V for images (N=468) and videos (N=234) that are derived from social movie scenes. These evaluations were compared with human evaluations (N=2254). The comparisons established that GPT-4V can achieve human-like social perceptual capabilities at the level of individual features as well as at the level of high-dimensional perceptual representations. We also modelled hemodynamic responses (N=97) to viewing socioemotional movie clips with feature annotations by human observers and GPT-4V. These results demonstrated that GPT-4V can also reproduce the social perceptual space at the neural level highly similar to reference human evaluations. These human-like social perceptual capabilities of LLMs could have wide range of real-life applications ranging from health care to business and would open exciting new avenues for behavioural and psychological research.
mCLAS adaptively rescues disease-specific sleep and wake phenotypes in neurodegeneration
Authors: Dias Inês , Baumann Christian R. , Noain Daniela 
Published: August 2024

AbstractSleep alterations are hallmarks of prodromal Alzheimer’s (AD) and Parkinson’s disease (PD), with fundamental neuropathological processes of both diseases showing susceptibility of change upon deep sleep modulation. However, promising pharmacological deep sleep enhancement results are hindered by specificity and scalability issues, thus advocating for noninvasive slow-wave activity (SWA) boosting methods to investigate the links between deep sleep and neurodegeneration. Accordingly, we have recently introduced mouse closed-loop auditory stimulation (mCLAS), which is able to successfully boost SWA during deep sleep in neurodegeneration models. Here, we aim at further exploring mCLAS’ acute effect onto disease-specific sleep and wake alterations in AD (Tg2576) and PD (M83) mice. We found that mCLAS adaptively rescues pathological sleep and wake traits depending on the disease-specific impairments observed at baseline in each model. Notably, in AD mice mCLAS significantly increases NREM long/short bout ratio, decreases vigilance state distances by decreasing transition velocities and increases the percentage of cumulative time spent in NREM sleep in the last three hours of the dark period. Contrastingly, in PD mice mCLAS significantly decreases NREM sleep consolidation, by potentiating faster and more frequent transitions between vigilance states, decreases average EMG muscle tone during REM sleep and increases alpha power in WAKE and NREM sleep. Overall, our results indicate that mCLAS selectively prompts an acute alleviation of neurodegeneration-associated sleep and wake phenotypes, by either potentiating sleep consolidation and vigilance state stability in AD or by rescuing bradysomnia and decreasing cortical hyperexcitability in PD. Further experiments assessing the electrophysiological, neuropathological and behavioural long-term effects of mCLAS in neurodegeneration may majorly impact the clinical establishment of sleep-based therapies.
Low extracellular pH protects cancer cells from ammonia toxicity
Authors: Dravecka Maria , Mikkola Ingvild , Johansen Terje , Seternes Ole Morten , Mejlvang Jakob 
Published: August 2024

AbstractAmmonia is a natural waste product of cellular metabolism which, through its lysosomotropic ability, can have detrimental effects on various cellular functions. Increased levels of ammonia were recently detected in the interstitial fluid of various tumours, substantiating that high ammonia concentrations are a pathophysiological condition in the tumour microenvironment, alongside hypoxia and acidosis. Since little is known about how cancer cells respond to elevated levels of ammonia in the tumour microenvironment, we investigated how a panel of cancer cell lines derived from solid tumours behaved when exposed to increasing concentrations of ammonia. We found that ammonia represses cell growth, induces genome instability, and inhibits lysosome-mediated proteolysis in a dose-dependent manner. Unexpectedly, we also found that small fluctuations in the pH of the extracellular environment, had a significant impact on the cytotoxic effects of ammonia. In summary, our data suggest that the balance of pH and ammonia within the interstitial fluids of cancerous tumours can have a significant impact on the behaviour and fate of cancer cells.
Refining Martini Force Field Interactions for Accurate Glycoprotein Modeling
Authors: Heidari Maziar , Sikora Mateusz , Hummer Gerhard 
Published: August 2024

AbstractCovalently attached sugar molecules play important roles as mediators of biomolecular interactions. Molecular dynamics simulations are an indispensable tool to explore these interactions at the molecular level. The large time and length scales involved frequently necessitate the use of coarse-grained representations, which heavily depend on the parameterization of sugar-protein interactions. Here, we adjust the sugar-protein interactions in the widely used Martini 2.2 force field to reproduce the experimental second virial coefficients between sugars and proteins. In simulations of two model proteins in glucose solutions with adjusted force field parameters, we observe weak protein-sugar interaction. The sugar molecules are thus acting mainly as crowding agents, in agreement with experimental measurements. The procedure to fine-tune sugar-protein interactions is generally applicable and could prove useful also for atomistic force fields.
Investigating the role of axonal localization of sex peptide receptor in post-mating responses of femaleDrosophila melanogaster
Authors: Zhang Tianmu , Zhou Xinyue , Kim Woo Jae 
Published: August 2024

ABSTRACTThis study elucidates the molecular mechanisms underlying the axonal localization of the sex peptide receptor, a pivotal G-protein coupled receptor in theDrosophila melanogasterpost-mating response cascade. Utilizing transgenic expression, neuronal labeling, and bioinformatics analyses, we demonstrate that the N-terminal domain of SPR is indispensable for its axonal targeting in bothDrosophilalarval ventral nerve cord neurons and mouse hippocampal neurons. Deletion of the N-terminal domain abolished axonal localization, highlighting its critical role in this process. Intriguingly, the C-terminal domain of SPR appears to play a subordinate role in axonal targeting. Bioinformatical analysis revealed a striking homology between the N-terminus of SPR and the Broad-complex, Tramtrack, and Bric-a-brac/poxvirus and zinc finger family of proteins. The BTB domain, a conserved protein-protein interaction domain within this family, is implicated in diverse cellular processes and axonal targeting. Further investigation into the role of the BTB domain-like region in SPR could provide valuable insights into the molecular underpinnings of axonal targeting and post-mating responses inDrosophila. This research contributes to our understanding of the intricate mechanisms governing GPCR localization and function in the context of reproductive biology and neuronal signaling.
RBN-2397, a PARP7 Inhibitor, Synergizes with Paclitaxel to Inhibit Proliferation and Migration of Ovarian Cancer Cells
Authors: Spirtos Alexandra N. , Aljardali Marwa W. , Challa Sridevi , Koul Sneh , Lea Jayanthi S. , Kraus W. Lee , Camacho Cristel V. 
Published: August 2024

AbstractObjectivesMono(ADP-ribosyl)ation (MARylation), a post translational modification of proteins, is emerging as an important regulator of the biology of cancer cells. PARP7 (TiPARP), a mono (ADP-ribosyl) transferase (MART), MARylates its substrate α-tubulin in ovarian cancer cells, promoting destabilization of microtubules, cell growth, and migration. Recent development of RBN-2397, a potent inhibitor that selectively acts on PARP7, has provided a new tool for exploring the role of PARP7 catalytic activity in biological processes. In this study, we investigated the role of PARP7 catalytic activity in the regulation of ovarian cancer cell biology via MARylation of α-tubulin.MethodsOvarian cancer cell lines (OVCAR4, OVCAR3) were treated with RBN-2397 and paclitaxel, both separately and in combination. Western blotting and immunoprecipitation confirmed the effects of RBN-2397 on α-tubulin MARylation and stabilization. Cell proliferation and migration were assessed, and α-tubulin stabilization was quantified using immunofluorescent imaging. RNA-sequencing was performed to assess the effects on gene expression changes.ResultsRBN-2397 inhibited PARP7 activity, decreasing α-tubulin MARylation, leading to its stabilization, and reducing cancer cell proliferation and migration. The addition of paclitaxel further enhanced these effects, highlighting a synergistic interaction between the two drugs. Mutating the site of PARP7-mediated MARylation on α-tubulin similarly resulted in microtubule stabilization and decreased cell migration in the presence of paclitaxel.ConclusionsThis study demonstrates that targeting PARP7 with RBN-2397, particularly in combination with paclitaxel, offers an effective strategy for inhibiting aggressive ovarian cancer cell phenotypes. Our findings underscore the potential of combining PARP7 inhibitors with established chemotherapeutics to enhance treatment efficacy in ovarian cancer.
CryoSCAPE: Scalable Immune Profiling Using Cryopreserved Whole Blood for Multi-omic Single Cell and Functional Assays
Authors: Heubeck Alexander T. , Phalen Cole , Kaul Neel , Wittig Peter J. , Garber Jessica , Weiss Morgan , Genge Palak C. , Thomson Zachary , Gustafson Claire , Reading Julian , Skene Peter J. 
Published: August 2024

AbstractBackgroundThe field of single cell technologies has rapidly advanced our comprehension of the human immune system, offering unprecedented insights into cellular heterogeneity and immune function. While cryopreserved peripheral blood mononuclear cell (PBMC) samples enable deep characterization of immune cells, challenges in clinical isolation and preservation limit their application in underserved communities with limited access to research facilities. We present CryoSCAPE (Cryopreservation for Scalable Cellular And Proteomic Exploration), a scalable method for immune studies of human PBMC with multi-omic single cell assays using direct cryopreservation of whole blood.ResultsComparative analyses of matched human PBMC from cryopreserved whole blood and density gradient isolation demonstrate the efficacy of this methodology in capturing cell proportions and molecular features. The method was then optimized and verified for high sample throughput using fixed single cell RNA sequencing and liquid handling automation with a single batch of 60 cryopreserved whole blood samples. Additionally, cryopreserved whole blood was demonstrated to be compatible with functional assays, enabling this sample preservation method for clinical research.ConclusionsThe CryoSCAPE method, optimized for scalability and cost-effectiveness, allows for high-throughput single cell RNA sequencing and functional assays while minimizing sample handling challenges. Utilization of this method in the clinic has the potential to democratize access to single-cell assays and enhance our understanding of immune function across diverse populations.
Understanding responses to multi-electrode epiretinal stimulation using a biophysical model
Authors: Vilkhu Ramandeep S. , Vasireddy Praful K. , Kish Kathleen E. , Gogliettino Alex R. , Lotlikar Amrith , Hottowy Pawel , Dabrowski Wladyslaw , Sher Alexander , Litke Alan M. , Mitra Subhasish , Chichilnisky E.J. 
Published: August 2024

AbstractObjectiveNeural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike. However, this multi-site activation hypothesis is difficult to verify experimentally.ApproachWe developed a biophysical model to study retinal ganglion cell (RGC) responses to multi-electrode stimulation and validated it using data collected fromex vivopreparations of the macaque retina using a microelectrode array (512 electrodes; 30µm pitch; 10µm diameter).ResultsFirst, the model was validated by using it to reproduce essential empirical findings from single-electrode recording and stimulation, including recorded spike voltage waveforms at multiple locations and sigmoidal responses to injected current. Then, stimulation with two electrodes was modeled to test how the positioning of the electrodes relative to the cell affected the degree of response nonlinearity. Currents passed through pairs of electrodes positioned near the cell body or far from the axon (>40 µm) exhibited approximately linear summation in evoking spikes. Currents passed through pairs of electrodes close to the axon summed linearly when their locations along the axon were similar, and nonlinearly otherwise. Over a range of electrode placements, several distinct, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. Similar trends were observed for three-electrode stimuli. All of these trends in the simulation were consistent with experimental observations.Significance. These findings support the multi-site activation hypothesis for nonlinear activation of neurons, providing a biophysical interpretation of previous experimental results and potentially enabling more efficient use of multi-electrode stimuli in future neural implants.
Phthalate exposure influences mating behavior and sperm morphology in an aquatic ecotoxicology model system
Authors: Guevara Bryan Lamberto , Patel Nadia , Tu Yi , Neiman Maurine 
Published: August 2024

AbstractPhthalates are a group of chemicals used to make plastics more durable, found in applications from cosmetics, lubricating oils, and flooring to soap, shampoo, and hairspray (CDC, 2021). Phthalates are also now known to be endocrine disruptors with connections to adverse reproductive outcomes in animals, including humans. Here, we evaluate the potential effects of a widely used phthalate ester, dimethyl phthalate (DMP), on male reproduction in a freshwater snail. DMP is found in industrial applications like solid rocket propellant as well as consumer products such as insect repellents and plastics. While there is some evidence that DMP negatively affects reproduction, especially in females, we still know very little about potential DMP effects on males. We addressed this important knowledge gap by testing the effects of DMP onPotamopyrgus antipodarum, a prosobranch snail native to New Zealand. These snails are very sensitive to water conditions and environmental chemicals, including endocrine-disrupting compounds, and are thus rising in prominence as water-quality sentinels and ecotoxicology models. We exposed experimental groups of maleP. antipodarumto one of three different concentrations of DMP and characterized mating behavior and sperm morphology as a function of DMP exposure. Differences in these traits were primarily observed between the males in the control versus the High (10-6M) DMP concentration group. As DMP exposure levels increased, we found that mating frequency ultimately decreased by more than 69% and that sperm morphology was increasingly altered relative to control males. Altogether, study outcomes suggest DMP exposure in male animals could have negative effects on reproduction, with particular relevance in aquatic and marine environments that are especially likely to harbor leached endocrine-disrupting chemicals.
Optimising experimental designs for model selection of ion channel drug binding mechanisms
Authors: Patten-Elliott Frankie , Lei Chon Lok , Preston Simon P. , Wilkinson Richard D. , Mirams Gary R. 
Published: August 2024

AbstractThe rapid delayed rectifier current carried by the human Ether-à-go-go-Related Gene (hERG) channel is susceptible to drug-induced reduction which can lead to an increased risk of cardiac arrhythmia. Establishing the mechanism by which a specific drug compound binds to hERG can help to reduce uncertainty when quantifying pro-arrhythmic risk. In this study, we introduce a methodology for optimising experimental voltage protocols to produce data that enable different proposed models for the drug-binding mechanism to be distinguished. We demonstrate the performance of this methodology via a synthetic data study. If the underlying model of hERG current is known exactly, then the optimised protocols generated show noticeable improvements in our ability to select the true model when compared to a simple protocol used in previous studies. However, if the model is not known exactly, and we assume a discrepancy between the data-generating hERG model and the hERG model used in fitting the models, then the optimised protocols become less effective in determining the ‘true’ binding dynamics. While the introduced methodology shows promise, we must be careful to ensure that, if applied in a real data study, we have a well-calibrated model of hERG current gating.
Widespread environment-specific causal effects detected in the UK Biobank
Authors: Knüsel Leona , Man Alice , Paré Guillaume , Kutalik Zoltán 
Published: August 2024

AbstractBackgroundMendelian Randomization (MR) is a widely used tool to infer causal relationships. Yet, little research has been conducted on the elucidation of environment specific causal effects, despite mounting evidence for the relevance of causal effect modifying environmental variables.MethodsTo investigate potential modifications of causal effects, we extended two-stage-least-squares MR to investigate interaction effects (2SLS-I). We first tested 2SLS-I in a wide range of realistic simulation settings including quadratic and environment-dependent causal effects. Next, we applied 2SLS-I to investigate how environmental variables such as age, socioeconomic deprivation, and smoking modulate causal effects between a range of epidemiologically relevant exposure (such as systolic blood pressure, education, and body fat percentage) - outcome (e.g. forced expiratory volume (FEV1), CRP, and LDL cholesterol) pairs (in up to 337’392 individuals of the UK biobank).ResultsIn simulations, 2SLS-I yielded unbiased interaction estimates, even in presence of non-linear causal effects. Applied to real data, 2SLS-I allowed for the detection of 182 interactions (P<0.001), with age, socioeconomic deprivation, and smoking being identified as important modifiers of many clinically relevant causal effects. For example, the positive causal effect of Triglycerides on systolic blood pressure was significantly attenuated in the elderly whilst the positive causal effect of Gamma-glutamyl transferase on CRP was intensified in smokers.ConclusionWe present 2SLS-I, a method to simultaneously investigate environment-specific and non-linear causal effects. Our results highlight the importance of environmental variables in modifying well-established causal effects.