bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociality shapes the adaptive response of breeders to harsh thermal environments? An experiment in a burying beetle
Authors: Ma Donghui , Ma Long , Versteegh Maaike A. , Komdeur Jan 
Published: November 2024

AbstractThe rapid pace of environmental change seems to outstrip the evolutionary response rates of many species. Physiological, morphological, and behavioral plasticity alone may also not suffice to cope with environments’ drastic changes, potentially hindering individuals’ ability to adapt. Therefore, it has been proposed that social flexibility may be a powerful mechanism for fast adaptation, but empirical evidence is lacking.We investigated the combined effects of manipulated social conditions and ambient temperature during the reproductive phase on parental care, reproductive success, and offspring performance of the burying beetle (Nicrophorus vespilloides), a facultative social breeding insect.We conducted a mixed factorial design experiment, establishing four categories of social conditions during breeding (no-care, unifemale-care, biparenta-care, and multiple-care) alongside two thermal conditions (benign: 20°C and harsh: 23°C). Additionally, dispersed larvae produced from each of these breeding conditions were allocated to climate rooms maintained at either 20°C or 23°C for pupation. Data on brood size, brood mass, dispersed larval weight, larval development duration, body size and lifespan of newly eclosed beetles, and parental care were collectedOur results showed that (1) harsh temperature and the without-care condition (i.e., no-care compared to the other three social conditions) reduced brood size, brood mass, body size of newly eclosed beetles; (2) social and ambient thermal conditions had interactive effects on dispersed larval weight, larval development duration, and newly eclosed beetles’ lifespan; and (3) harsh temperature reduced both individual and total parental care, whereas sociality had opposing effects: individual care decreased, but total care increased from unifemale-care to biparental-care and multiple-care conditions.Our findings shed light on the critical role of sociality in modulating the adaptive response of individuals to harsh thermal environments, one of the ecological problems exacerbated by ongoing global warming.
Complementation of a human disease phenotype in vitro by intercellular mRNA transfer
Authors: Haimovich Gal , Dasgupta Sandipan , Ravi Anand Govindan , Gerst Jeffrey E. 
Published: November 2024

AbstractThere is growing evidence that full-length mRNAs undergo intercellular transfer through long, thin cytoplasmic connections called tunneling nanotubes (TNTs), but whether transferred mRNAs are translated and effect cellular changes post-transfer is unknown. Using multiple lines of evidence, we show that transferred mRNAs undergo translation and can fully complement the phenotype of genetic mutationsin vitro. For example, the human peroxisome biogenesis disorder, Zellweger Syndrome, results from mutations in genes like PEX5 and PEX6. We demonstrate that the co-culture of patient-derived PEX6 mutant fibroblasts or PEX5 knock-out cells with wild-type cells leads tode novoperoxisome biogenesis. Complementation occurs by TNT-mediated mRNA transfer and translation in acceptor cells and not by peroxisome transfer. We provide additional examples of genetic complementation via transfer of mRNAs encoding the HSF1 transcription factor or CRE recombinase. Our study provides evidence for the physiological significance of mRNA transfer and suggests a new approach for mRNA therapeutics.Abstract Figure
Single Objective Light Sheet Microscopy allows high-resolutionin vivobrain imaging of Drosophila
Authors: Tassara Francisco J. , Barella Mariano , Simó Lourdes , Folgueira Serrao M. Mailén , Rodríguez-Caron Micaela , Ispizua Juan Ignacio , Ellisman Mark H. , de la Iglesia Horacio O. , Ceriani M. Fernanda , Gargiulo Julián 
Published: November 2024

AbstractIn vivoimaging of dynamic sub-cellular brain structures inDrosophila melanogasteris key to understanding several phenomena in neuroscience. However, its implementation has been hindered by a trade-off between spatial resolution, speed, photobleaching, phototoxicity, and setup complexity required to access the specific target regions of the small brain ofDrosophila. Here, we present a single objective light-sheet microscope, customized forin vivoimaging of adult flies and optimized for maximum resolution. With it, we imaged the axonal projections of small lateral ventral neurons (known as s-LNvs) in intact adult flies. We imaged the plasma membrane, mitochondria, and dense-core vesicles with high spatial resolution up to 370 nm, ten times lower photobleaching than confocal microscopy, lower invasiveness and complexity in sample mounting than alternative light-sheet technologies, and without relying on phototoxic pulsed infrared lasers. This unique set of features paves the way for new long-term, dynamic studies in the brains of living flies.
Real-Time Spatiotemporal Filtering for Artifact-Free EEG during Electrical Neurostimulation
Authors: Menrath David , Woller Joshua P. , Gharabaghi Alireza 
Published: November 2024

AbstractCombining electrical neurostimulation with electroencephalography (EEG) for adaptive neurostimulation remains challenging due to the presence of stimulation artifacts in the recorded signal. Interpretation of EEG activity concurrent with stimulation requires real-time filtering of this noisy signal. While traditional frequency domain filters can suppress activity within frequency bands, they fail to differentiate sources in situations when there is a shared frequency characteristic between brain activity and stimulation signal. Here we present a new real-time denoising approach that combines spatial filtering and dynamic filter application. The spatiotemporal filter can suppress stimulation artifacts that share frequency bands with the brain signal in real-time while preserving the full spectral power. The spatial filter is also dynamically updated to account for possible changes in artifact topography. Finally, the filter is robust to changes of stimulation intensity, frequency and duration, enabling reliable denoising performance for inclusion in brain state-based closed-loop stimulation.
Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism
Authors: Baytas Ozan , Davidson Shawn M. , Kauer Julie A. , Morrow Eric M. 
Published: November 2024

AbstractRecessive loss-of-function mutations in the mitochondrial enzyme Glutamate Pyruvate Transaminase 2 (GPT2) cause intellectual disability in children. Given this cognitive disorder, and because glutamate metabolism is tightly regulated to sustain excitatory neurotransmission, here we investigate the role of GPT2 in synaptic function. GPT2 catalyzes a reversible reaction interconverting glutamate and pyruvate with alanine and alpha-ketoglutarate, a TCA cycle intermediate; thereby, GPT2 may play an important role in linking mitochondrial tricarboxylic acid (TCA) cycle with synaptic transmission. In mouse brain, we find that GPT2 is enriched in mitochondria of synaptosomes (isolated synaptic terminals). Loss of Gpt2 in mouse appears to lead to reprogramming of glutamate and glutamine metabolism, and to decreased glutamatergic synaptic transmission. Whole-cell patch-clamp recordings in pyramidal neurons of CA1 hippocampal slices fromGpt2-null mice reveal decreased excitatory post-synaptic currents (mEPSCs) without changes in mEPSC frequency, or importantly, changes in inhibitory post-synaptic currents (mIPSCs). Additional evidence of defective glutamate release included reduced levels of glutamate released fromGpt2-null synaptosomes measured biochemically. Glutamate release from synaptosomes was rescued to wild-type levels by alpha-ketoglutarate supplementation. Additionally, we observed evidence of altered metabolism in isolatedGpt2-null synaptosomes: decreased TCA cycle intermediates, and increased glutamate dehydrogenase activity. Notably, alterations in the TCA cycle and the glutamine pool were alleviated by alpha-ketoglutarate supplementation. In conclusion, our data support a model whereby GPT2 mitochondrial activity may contribute to glutamate availability in pre-synaptic terminals, thereby highlighting potential interactions between pre-synaptic mitochondrial metabolism and synaptic transmission.
Response of neuronal populations to phase-locked stimulation: model-based predictions and validation
Authors: Mirkhani Nima , McNamara Colin G. , Oliviers Gaspard , Sharott Andrew , Duchet Benoit , Bogacz Rafal 
Published: November 2024

AbstractBackgroundModulation of neuronal oscillations holds promise for the treatment of neurological disorders. Nonetheless, stimulating neuronal populations in a continuous open-loop manner can lead to side effects and suboptimal efficiency. Closed-loop strategies such as phase-locked stimulation aim to address these shortcomings by offering a more targeted modulation. While theories have been developed to understand the neural response to stimulation, their predictions have not been thoroughly tested using experimental data.ObjectiveWe aimed to test the predictions of a mathematical model regarding the response of neuronal populations to phase-locked stimulation.MethodsUsing a coupled oscillator model, we expanded on two key predictions describing the response to stimulation as a function of the phase and amplitude of ongoing neural activity. To investigate these predictions, we analyzed electrocorticogram (ECoG) recordings from a previously conducted study in Parkinsonian rats, and extracted the corresponding phase and response curves.ResultsWe demonstrated that the amplitude response to stimulation is strongly correlated to the derivative of the phase response (ρ> 0.8) in all animals except one, thereby validating a key model prediction. The second prediction postulated that the stimulation becomes ineffective when the network synchrony is high, a trend that appeared missing in the data. Our analysis explained this discrepancy by showing that the neural populations in Parkinsonian rats did not reach the level of synchrony for which the theory would predict ineffective stimulation.ConclusionsOur results highlight the potential of fine-tuning stimulation paradigms informed by mathematical models that consider both the ongoing phase and amplitude of the targeted neural oscillation.
Long noncoding RNAHSCHARMEpromotes the maturation of stem cells-derived cardiomyocytes by controlling gene regulatory networks altered in human cardiomyopathies
Authors: Buonaiuto Giulia , Desideri Fabio , Storari Giulio , Palma Alessandro , Santini Tiziana , Trisciuoglio Daniela , Ballarino Monica 
Published: November 2024

ABSTRACTA growing body of evidence suggests that tissue-specific long noncoding RNAs (lncRNA) play pivotal roles in the heart. Here, we exploited the synteny between the mouse and human genomes to identify the novel lncRNAHSCHARME(HumanSyntenic CHARME) and combined single-cell transcriptomics, CAGE-seq data, RNA-FISH imaging and CRISPR-Cas9 genome editing to document its role in cardiomyogenesis. We found that the functional inactivation ofHSCHARMEin hiPSC-derived cardiomyocytes (CM) impairs the expression of calcium handling and contraction genes, with a consequent decline of CM maturation and contractile functions. Consistent with a possible association with disease, large-scale analysis of the lncRNA expression across cardiomyopathy patients revealed increased levels ofHSCHARMEin hypertrophic (HCM) and dilated (DCM) hearts and identified a subset of diseased-associated targets whose expression can be modulated throughHSCHARMEdosage. Overall, our data unlock the potential ofHSCHARMEas a novel non-coding regulator of CM physiology and open new possibilities for the therapeutic application of the lncRNA in disease.
In VitroFertilization induces reproductive changes in male mouse offspring and has multigenerational effects
Authors: Rhon-Calderon Eric A. , Hemphill Cassidy N. , Savage Alexandra J. , Riesche Laren , Schultz Richard M. , Bartolomei Marisa S. 
Published: November 2024

AbstractIn vitrofertilization (IVF) is a non-coital method of conception used to treat human infertility. Although IVF is viewed as largely safe, it is associated with adverse outcomes in the fetus, placenta, and adult offspring life. Because studies focusing on the effect of IVF on the male reproductive system are limited, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated three developmental stages: 18.5-day fetuses and 12- and 39-week-old adults. Regardless of age, we observed changes in testicular-to-body weight ratios, serum testosterone levels, testicular morphology, gene expression, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF and naturally conceived males with wild-type females. Offspring from IVF males exhibited decreased fetal weight-to-placental weight ratios and changes in placenta morphology regardless of sex. At 12-weeks-of-age, offspring showed higher body weights and differences in glucose, triglycerides, insulin, total cholesterol, HDL and LDL/VLDL levels. Both sexes showed changes in gene expression in liver, testes and ovaries, and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations and transmit defects multigenerationally.
Employing biological sex as a primary variable can restrict our understanding of behavioral diversity (and sex differences) in psychostimulant activity
Authors: Yao Gabriella , Job Martin O 
Published: November 2024

AbstractBackgroundIn addition to representing distinct biological sex groups, males and females are also individuals expressing behavioral diversity. Our MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model suggests that, with respect to behavior, grouping according to the individual reveals groups with differences that exceed biological sex-related differences, but this needs further clarification. We hypothesized that, compared to the current model (grouping by biological sex), the MISSING model (grouping by individual attributes) was the more effective grouping strategy to identify behavioral diversity.MethodsWe conducted experiments in rats to determine the locomotor activity (in 90 min) following intraperitoneal injections of saline (n = 12 males, n = 11 females) and cocaine (n = 8 males, n = 11 females). For the current model, we compared males versus females using unpaired t-tests. For the MISSING model, we identified clusters of individuals (males and females) using normal mixtures clustering analysis of several behavioral variables and employed unpaired t-tests to compare clusters and Two-way ANOVA to determine if there were any SEX by cluster interactions. For both models, we employed linear regression analysis to compare relationships between variables and Two-way repeated measures ANOVA to analyze locomotor activity time course.ResultsFor both the saline and cocaine groups, the MISSING model identified two behavioral clusters with differences that exceeded any differences due to biological sex.ConclusionsThe MISSING model suggests that employing biological sex as a primary variable can obscure our understanding of sex and individual differences in psychostimulant activity.
A high-quality genome of the mass-blooming desert plantCistanthe longiscapaand its photosynthetic behavior related to drought and life history
Authors: Chomentowska Anri , Raimondeau Pauline , Wei Lan , Jose Eleanor G.D. , Dauerman Sophie G. , Davis Virginia Z. , Moreira-Muñoz Andrés , Peralta Iris E. , Edwards Erika J. 
Published: November 2024

SummaryCrassulacean acid metabolism (CAM) photosynthesis has independently evolved many times in arid-adapted plant lineages.Cistanthe longiscapa(Montiaceae), a desert mass-blooming annual, can upregulate CAM facultatively upon stress such as drought. Few studies, however, consider life history stages when measuring CAM activity or its facultative onset.To test the effect of drought and flowering on photosynthetic activity, we assayedCistantheindividuals in fully-watered and drought conditions, as well as fully-watered individuals at pre-flowering and flowering life stages. We assembled and annotated a chromosome-scale genome ofC. longiscapaand compared it with the genome ofPortulaca amilisand analyzed differential gene expression.Results show significantly upregulated CAM in drought conditions as compared to fully-watered conditions; furthermore, flowering individuals showed slightly higher CAM activity as compared to pre-flowering plants, even when fully-watered. Differential gene expression analyses provide preliminary support for the possible co-regulation of CAM expression and reproduction.We emphasize the potentially missed significance of life history in the CAM literature, and consider how the CAM biochemical module could become co-opted into other plant behaviors and responses, such as the shift to reproduction or flowering in annuals.
Differentially expressed growth factors and cytokines drive phenotypic changes in transmissible cancers
Authors: Maskell Kathryn G. , Schönbichler Anna , Flies Andrew S. , Patchett Amanda L. 
Published: November 2024

AbstractThe Tasmanian devil is threatened by two deadly transmissible Schwann cell cancers. A vaccine to protect Tasmanian devils from both devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2), and improved understanding of the cancer cell biology, could support improved conservation actions. Previous transcriptomic analysis has implicated phenotypic cellular plasticity as a potential immune escape and survival mechanism of DFT1 cells. This phenotypic plasticity facilitates transition from a myelinating Schwann cell to a repair Schwann cell phenotype that exhibits mesenchymal characteristics. Here, we have identified cytokines and growth factors differentially expressed across DFT cell phenotypes and investigated their role in driving phenotypic plasticity and oncogenic properties of DFT cells. Our results show that NRG1, IL16, TGFβ1, TGFβ2 and PDGFAA/AB proteins have significant and distinct effects on the proliferation rate, migratory capacity and/or morphology of DFT cells. Specifically, PDGFR signalling, induced by PDGFAA/AB, was a strong enhancer of cell proliferation and migration, while TGFβ1 and TGFβ2 induced epithelial-mesenchymal transition (EMT)-like changes, inhibited proliferation and increased migratory capacity. These findings suggest complex interactions between cytokine signalling, phenotypic plasticity, growth and survival of DFTs. Signalling pathways implicated in the propagation of DFT are potential targets for therapeutic intervention and vaccine development for Tasmanian devil conservation.
The Wnt1-Cre2 transgene causes aberrant recombination in non-neural crest cell types
Authors: Gandhi Shashank , Du Emily J. , Pangilinan Edivinia S. , Harland Richard M. 
Published: November 2024

AbstractThe Wnt1-Cre2 driver, designed to address the effect of Wnt1 overactivation in the ventral neural tube in the original Wnt1-Cre line, was recently shown to have ectopic expression in the male germline. When crossed with a reporter mouse, we observed fluorescent protein expression in non-neural-crest cell types in the gut. Here, we characterize the pattern of Cre-mediated recombination in the Wnt1-Cre2 driver using three transgenic reporter lines. We find aberrant reporter activation in the gut endoderm in embryonic and postnatal timepoints, starting as early as E8.5. This pattern of recombination was independent of the age, sex, and type of reporter line used, with the Wnt1-Cre2 allele inherited from either sires or dams resulting in ectopic fluorescence in the intestinal epithelium. We also detect reporter activity in the ventral neural tube. However, expression in the neural crest and its derivatives remained consistent with previous studies. We further quantify differences in the non-specific recombination observed across reporter lines using flow cytometry. Interestingly, the penetrance of reporter activation between reporter lines was different, with R26RmTmGshowing less ectopic activation than the R26RtdTomand R26ReYFPlines. Finally, we propose a potential mechanism whereby genes surrounding the Wnt1-Cre2 insertion site on mouse chromosome 2 contribute to its Wnt1-independent activation in the endoderm. Taken together, our results suggest that users should exercise caution when using the Wnt1-Cre2 driver line for neural crest studies in the mouse.
Estimating behavioural relaxation induced by COVID-19 vaccines in the first months of their rollout
Authors: Li Yuhan , Gozzi Nicolò , Perra Nicola 
Published: November 2024

AbstractThe initial rollout of COVID-19 vaccines has been challenged by logistical issues, limited availability of doses, scarce healthcare capacity, spotty acceptance, and variants of concern. Non-pharmaceutical interventions (NPIs) have been critical to support these phases. However, vaccines may have prompted behavioural relaxation, potentially reducing NPIs adherence. Epidemic models have explored this phenomenon, but they have not been validated against data. Moreover, recent surveys provide conflicting results on the matter. The extent of behavioural relaxation induced by COVID-19 vaccines is still unclear. Here, we aim to study this phenomenon in four regions. We implement five realistic epidemic models which include age structure, multiple virus strains, NPIs, and vaccinations. One of the models acts as a baseline, while the others extend it including different behavioural relaxation mechanisms. First, we calibrate the baseline model and run counterfactual scenarios to quantify the impact of vaccinations and NPIs. Our results confirm the critical role of both in reducing infection and mortality rates. Second, we calibrate the behavioural models and compare them to each other and to the baseline using different metrics. Including behavioural relaxation leads to a better fit of weekly deaths in three regions. However, the improvements are limited to a 2 − 10% reduction in weighted mean absolute percentage errors and these gains are generally offset by models’ increased complexity. Overall, we do not find clear signs of behavioural relaxation induced by COVID-19 vaccines on weekly deaths. Furthermore, our results suggest that if this phenomenon occurred, it generally involved only a firm minority of the population. Our work contributes to the retrospective validation of epidemic models developed amid the COVID-19 Pandemic and underscores the issue of non-identifiability of complex social mechanisms.